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Wu J, Xu JH, Zou HQ, Ouyang YJ, Li SJ, Wu L, Zhang J, Yin MJ, Ye DQ, Ni JD. Assessing Association Between Circulating Bilirubin Levels and the Risk of Frailty: An Observational and Mendelian Randomization Study. J Cachexia Sarcopenia Muscle 2025; 16:1-11. [PMID: 39582374 DOI: 10.1002/jcsm.13642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 10/12/2024] [Accepted: 10/17/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND Bilirubin is a by-product of haemoglobin breakdown and has been reported to be a potent antioxidant recently. While elevated levels of bilirubin have been linked to a reduced risk of various diseases, their role remains unknown in frailty. This study aims to explore the relationship between serum bilirubin levels and the risk of frailty. METHODS This cohort study included 442 223 White British participants (aged 39 to 73 years) with an available frailty index at baseline (2006 to 2010) from the UK Biobank. The associations of total/direct bilirubin levels with the continuous frailty index were analysed by multivariable linear regression, and multivariable logistic regression was used after classifying frailty outcomes into non-frailty, pre-frailty and frailty. A Mendelian randomization (MR) analysis was applied to evaluate the association of genetically predicted bilirubin levels with frailty risk. RESULTS The prevalence rates of both pre-frailty and frailty were 46.17% and 12.49%, respectively, with higher rates observed in women than in men (pre-frailty: 47.33% vs. 44.79%, frailty: 13.64% vs. 11.13%, respectively). There was a non-linear negative association between total bilirubin levels and frailty indexes (p < 0.0001). Mildly elevated total bilirubin levels had protective effects against pre-frailty (OR = 0.863, 95% CI: 0.849 to 0.879, p < 0.001) and frailty (OR = 0.660, 95% CI: 0.641 to 0.679, p < 0.001). Increased total bilirubin levels were more beneficial for women with frailty risk (percent changes per SD μmol/L = -0.37%, 95% CI: -0.40% to -0.34%). The MR analysis revealed a negative association between genetically predicted total/direct bilirubin levels and frailty risk (both p < 0.0001). CONCLUSIONS Circulating total/direct bilirubin levels were negatively associated with frailty risk in White British individuals. Mildly elevated total bilirubin levels were more beneficial for women subpopulation.
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Affiliation(s)
- Jun Wu
- Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital, Guangdong Medical University, Dongguan, China
| | - Jia-Hao Xu
- Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital, Guangdong Medical University, Dongguan, China
| | - Hao-Qi Zou
- Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital, Guangdong Medical University, Dongguan, China
| | - Yi-Jiang Ouyang
- Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital, Guangdong Medical University, Dongguan, China
| | - Shang-Jie Li
- Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital, Guangdong Medical University, Dongguan, China
| | - Liang Wu
- Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital, Guangdong Medical University, Dongguan, China
| | - Jie Zhang
- School of Public Health, Anhui University of Science and Technology, Hefei, Anhui, China
| | - Ming-Juan Yin
- Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital, Guangdong Medical University, Dongguan, China
| | - Dong-Qing Ye
- School of Public Health, Anhui University of Science and Technology, Hefei, Anhui, China
| | - Jin-Dong Ni
- Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital, Guangdong Medical University, Dongguan, China
- Precision Key Laboratory of Public Health, Guangdong Medical University, Dongguan, China
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Niwa T, Saeki C, Saito M, Oikawa T, Kamioka H, Kanai T, Ueda K, Nakano M, Torisu Y, Saruta M, Tsubota A. Impact of frailty and prevalent fractures on the long-term prognosis of patients with cirrhosis: a retrospective study. Sci Rep 2025; 15:186. [PMID: 39747234 PMCID: PMC11696115 DOI: 10.1038/s41598-024-83984-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 12/18/2024] [Indexed: 01/04/2025] Open
Abstract
Frailty and fractures are closely associated with adverse clinical outcomes. This retrospective study investigated the prognostic impact of frailty, prevalent fractures, and the coexistence of both in patients with cirrhosis. Frailty was defined according to the Fried frailty phenotype criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Prevalent fractures were assessed using questionnaires and lateral thoracolumbar spine radiographs. Cumulative survival rates were compared between the frailty and non-frailty groups, fracture and non-fracture groups, and all four groups stratified by the presence or absence of frailty and/or prevalent fractures. Among 189 patients with cirrhosis, 70 (37.0%) and 74 (39.2%) had frailty and prevalent fractures, respectively. The median observation period was 64.4 (38.6-71.7) months, during which 50 (26.5%) liver disease-related deaths occurred. Multivariate analysis identified frailty and prevalent fractures as significant independent prognostic factors in the overall cohort (p < 0.001 and p = 0.003, respectively). The cumulative survival rates were lower in the frailty or fracture groups than in the non-frailty or non-fracture groups, respectively, in the overall cohort and in patients with compensated and decompensated cirrhosis. Patients with both frailty and prevalent fractures showed the lowest cumulative survival rates, whereas those without these comorbidities showed the highest cumulative survival rates among the four stratified groups. Frailty and prevalent fractures were independently associated with mortality in patients with cirrhosis. Additionally, the coexistence of both comorbidities worsened the prognosis.
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Affiliation(s)
- Takashi Niwa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan
| | - Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan.
| | - Mitsuru Saito
- Department of Orthopedic Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroshi Kamioka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Tomoya Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan
| | - Kaoru Ueda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Masanori Nakano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan
| | - Yuichi Torisu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Akihito Tsubota
- Research Center for Medical Science, The Jikei University School of Medicine, Tokyo, Japan.
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Lin Y, Cao X, Zhu H, Chen X. Association of dietary inflammatory index, composite dietary antioxidant index, and frailty in elderly adults with diabetes. Eur J Med Res 2024; 29:480. [PMID: 39354551 PMCID: PMC11446060 DOI: 10.1186/s40001-024-02083-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 09/24/2024] [Indexed: 10/03/2024] Open
Abstract
BACKGROUND We aimed to examine the relationship of 2 dietary scores [dietary inflammatory index (DII) and composite dietary antioxidant index (CDAI)] with frailty in elderly adults with diabetes. METHODS Data were gathered from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. The frailty index was calculated using 49 deficits across various systems to define frailty. To examine the relationship of 2 dietary scores (DII and CDAI) with frailty in elderly adults with diabetes, multiple logistic regression analyses were performed. In logistic regression model, DII and CDAI were calculated as both continuous and tertiles. Subgroup analyses were performed to demonstrate stability of results. Restricted cubic splines were utilized to examine the non-linear correlations. RESULTS A total of 2,795 elderly adults with diabetes were included in this study. In the multivariate logistic regression model, the odds ratio (OR) of DII for risk of frailty was 1.08 (95% CI 1.02-1.15) and the OR of CDAI for risk of frailty was 0.96 (95% CI 0.93-0.99). The ORs of DII for risk of frailty were 1.36 (95% CI 1.09-1.70) and 1.33 (95% CI 1.04-1.70) for tertiles 2 and 3, respectively (p for trend 0.027). The ORs of CDAI for risk of frailty were 0.94 (95% CI 0.75-1.17) and 0.75 (95% CI 0.58-0.98) for tertiles 2 and 3, respectively (p for trend 0.036). The subgroup analysis demonstrated reliable and enduring connections between 2 dietary scores and frailty (all p for interaction > 0.05). In the restricted cubic spline analyses, we discovered the non-linear relationship between DII and frailty (P for nonlinearity = 0.045) and linear relationship between CDAI and frailty (P for nonlinearity = 0.769). CONCLUSION The research showed connections between 2 dietary scores (DII and CDAI) and frailty as measured by frailty index in elderly adults with diabetes.
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Affiliation(s)
- Yi Lin
- Department of Endocrinology, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, China
| | - Xiaohua Cao
- Department of Endocrinology, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, China
| | - Haihui Zhu
- Department of Endocrinology, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, China
| | - Xiyi Chen
- Department of Cardiovascular and Thoracic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
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Arauna D, Navarrete S, Albala C, Wehinger S, Pizarro-Mena R, Palomo I, Fuentes E. Understanding the Role of Oxidative Stress in Platelet Alterations and Thrombosis Risk among Frail Older Adults. Biomedicines 2024; 12:2004. [PMID: 39335518 PMCID: PMC11429027 DOI: 10.3390/biomedicines12092004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/14/2024] [Accepted: 08/21/2024] [Indexed: 09/30/2024] Open
Abstract
Frailty and cardiovascular diseases are increasingly prevalent in aging populations, sharing common pathological mechanisms, such as oxidative stress. The evidence shows that these factors predispose frail individuals to cardiovascular diseases but also increase the risk of thrombosis. Considering this background, this review aims to explore advances regarding the relationship between oxidative stress, platelet alterations, and cardiovascular diseases in frailty, examining the role of reactive oxygen species overproduction in platelet activation and thrombosis. The current evidence shows a bidirectional relationship between frailty and cardiovascular diseases, emphasizing how frailty not only predisposes individuals to cardiovascular diseases but also accelerates disease progression through oxidative damage and increased platelet function. Thus, oxidative stress is the central axis in the increase in platelet activation and secretion and the inadequate response to acetylsalicylic acid observed in frail people by mitochondrial mechanisms. Also, key biomarkers of oxidative stress, such as isoprostanes and derivate reactive oxygen metabolites, can be optimal predictors of cardiovascular risk and potential targets for therapeutic intervention. The potential of antioxidant therapies in mitigating oxidative stress and improving cardiovascular clinical outcomes such as platelet function is promising in frailty, although further research is necessary to establish the efficacy of these therapies. Understanding these mechanisms could prove essential in improving the health and quality of life of an aging population faced with the dual burden of frailty and cardiovascular diseases.
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Affiliation(s)
- Diego Arauna
- Thrombosis Research and Healthy Aging Center, Department of Clinical Biochemistry and Immunohematology, Interuniversity Center for Healthy Aging (CIES), Interuniversity Network of Healthy Aging in Latin America and Caribbean (RIES-LAC), Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile
| | - Simón Navarrete
- Thrombosis Research and Healthy Aging Center, Department of Clinical Biochemistry and Immunohematology, Interuniversity Center for Healthy Aging (CIES), Interuniversity Network of Healthy Aging in Latin America and Caribbean (RIES-LAC), Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile
| | - Cecilia Albala
- Unidad de Nutrición Pública, Instituto de Nutrición y Tecnología de los Alimentos, Interuniversity Center for Healthy Aging, Universidad de Chile, Santiago 7810000, Chile
| | - Sergio Wehinger
- Thrombosis Research and Healthy Aging Center, Department of Clinical Biochemistry and Immunohematology, Interuniversity Center for Healthy Aging (CIES), Interuniversity Network of Healthy Aging in Latin America and Caribbean (RIES-LAC), Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile
| | - Rafael Pizarro-Mena
- Facultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Sede Los Leones, Santiago 7500000, Chile
- Interuniversity Network of Healthy Aging in Latin America and Caribbean (RIES-LAC), Santiago 7810000, Chile
| | - Iván Palomo
- Thrombosis Research and Healthy Aging Center, Department of Clinical Biochemistry and Immunohematology, Interuniversity Center for Healthy Aging (CIES), Interuniversity Network of Healthy Aging in Latin America and Caribbean (RIES-LAC), Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile
| | - Eduardo Fuentes
- Thrombosis Research and Healthy Aging Center, Department of Clinical Biochemistry and Immunohematology, Interuniversity Center for Healthy Aging (CIES), Interuniversity Network of Healthy Aging in Latin America and Caribbean (RIES-LAC), Faculty of Health Sciences, Universidad de Talca, Talca 3460000, Chile
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Molinari P, Caldiroli L, Abinti M, Nardelli L, Armelloni S, Cesari M, Castellano G, Vettoretti S. Frailty Is Associated with Malnutrition-Inflammation Syndrome in Older CKD Patients. Nutrients 2024; 16:2626. [PMID: 39203763 PMCID: PMC11356796 DOI: 10.3390/nu16162626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 08/04/2024] [Accepted: 08/07/2024] [Indexed: 09/03/2024] Open
Abstract
Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition-inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried's frailty phenotype (FP), while malnutrition-inflammation syndrome was assessed using the Malnutrition-Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1). A total of 48 patients were frail, and mean eGFR was comparable in both frail and non-frail patients (24 ± 10 vs. 25 ± 11 mL/min/1.73 m2; p = 0.63). Frail patients had higher MIS (6 [4-11] vs. 4 [3-5]; p < 0.0001) but cytokine concentrations were comparable in both groups. At multivariate regression, FP was independently associated with MIS, age, gender and pre-albumin but not with cytokines. However, we found some associations between inflammatory cytokines and some specific frailty criteria: weight loss and slowness were associated with MCP-1 (respectively p = 0.049 and p < 0.0001) and weakness with IL-6 (p = 0.005); in conclusion, in older patients with advanced CKD, frailty is strictly associated with malnutrition-inflammation syndrome but not with circulating inflammatory cytokines.
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Affiliation(s)
- Paolo Molinari
- Unit of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (P.M.); (M.A.); (L.N.); (S.A.); (G.C.); (S.V.)
| | - Lara Caldiroli
- Unit of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (P.M.); (M.A.); (L.N.); (S.A.); (G.C.); (S.V.)
| | - Matteo Abinti
- Unit of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (P.M.); (M.A.); (L.N.); (S.A.); (G.C.); (S.V.)
| | - Luca Nardelli
- Unit of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (P.M.); (M.A.); (L.N.); (S.A.); (G.C.); (S.V.)
| | - Silvia Armelloni
- Unit of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (P.M.); (M.A.); (L.N.); (S.A.); (G.C.); (S.V.)
| | - Matteo Cesari
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy;
| | - Giuseppe Castellano
- Unit of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (P.M.); (M.A.); (L.N.); (S.A.); (G.C.); (S.V.)
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy;
| | - Simone Vettoretti
- Unit of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, 20122 Milan, Italy; (P.M.); (M.A.); (L.N.); (S.A.); (G.C.); (S.V.)
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El Assar M, Rodríguez-Sánchez I, Álvarez-Bustos A, Rodríguez-Mañas L. Biomarkers of frailty. Mol Aspects Med 2024; 97:101271. [PMID: 38631189 DOI: 10.1016/j.mam.2024.101271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/19/2024]
Abstract
Several biomarkers have been proposed to identify frailty, a multisystemic age-related syndrome. However, the complex pathophysiology and the absence of a consensus on a comprehensive and universal definition make it challenging to pinpoint a singular biomarker or set of biomarkers that conclusively characterize frailty. This review delves into the main laboratory biomarkers, placing special emphasis on those associated with various pathways closely tied to the frailty condition, such as inflammation, oxidative stress, mitochondrial dysfunction, metabolic and endocrine alterations and microRNA. Additionally, we provide a summary of different clinical biomarkers encompassing different tools that have been proposed to assess frailty. We further address various imaging biomarkers such as Dual Energy X-ray Absorptiometry, Bioelectrical Impedance analysis, Computed Tomography and Magnetic Resonance Imaging, Ultrasound and D3 Creatine dilution. Intervention to treat frailty, including non-pharmacological ones, especially those involving physical exercise and nutrition, and pharmacological interventions, that include those targeting specific mechanisms such as myostatin inhibitors, insulin sensitizer metformin and with special relevance for hormonal treatments are mentioned. We further address the levels of different biomarkers in monitoring the potential positive effects of some of these interventions. Despite the availability of numerous biomarkers, their performance and usefulness in the clinical arena are far from being satisfactory. Considering the multicausality of frailty, there is an increasing need to assess the role of sets of biomarkers and the combination between laboratory, clinical and image biomarkers, in terms of sensitivity, specificity and predictive values for the diagnosis and prognosis of the different outcomes of frailty to improve detection and monitoring of older people with frailty or at risk of developing it, being this a need in the everyday clinical practice.
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Affiliation(s)
- Mariam El Assar
- Fundación para la Investigación Biomédica del Hospital Universitario de Getafe, Madrid, Spain; Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
| | | | - Alejandro Álvarez-Bustos
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
| | - Leocadio Rodríguez-Mañas
- Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain; Servicio de Geriatría, Hospital Universitario de Getafe, Madrid, Spain.
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Li X, Wang Q, Ma T, Chang X, Xue Y, Zhang Y, Liu W, Zhang Y, Zhao Y. Dietary inflammatory index, dietary total antioxidant capacity, and frailty among older Chinese adults. J Nutr Health Aging 2024; 28:100168. [PMID: 38341967 DOI: 10.1016/j.jnha.2024.100168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 01/18/2024] [Indexed: 02/13/2024]
Abstract
OBJECTIVES Frailty is an age-related syndrome associated with poor health outcomes. Studies in developed countries indicate that the dietary inflammatory index (DII) and dietary total antioxidant capacity (DTAC) are important dietary factors influencing the risk of frailty in older adults. However, few studies have explored the association between DII, DTAC, and frailty among older Chinese adults. The objective of the current study was to examine whether DII and DTAC were associated with pre-frailty or frailty among older Chinese adults. DESIGN A cross-sectional study. SETTING Community-based. PARTICIPANTS We included 6414 participants aged ≥60 years. MEASUREMENTS Dietary intake was assessed using a validated food frequency questionnaire (FFQ). The DII and energy-adjusted DII (E-DII) were calculated using food parameters. DTAC was estimated using two widely adopted antioxidant scores: DTAC based on ferric reducing antioxidant power and dietary antioxidant quality score (DAQS) obtained from vitamins (vitamins A, C, and E) and minerals (zinc and selenium) with antioxidant functions. Frailty was assessed using the frailty index (FI) calculated from 28 health-related deficits. Individuals were classified as robust (FI ≤ 0.10), pre-frailty (FI > 0.10 to <0.25), or frailty (FI ≥ 0.25). Multiple logistic regression models were used to evaluate the associations of DII and DTAC with pre-frailty and frailty. RESULTS After adjusting for confounding factors, individuals in the highest DII quintile (Q5) were more likely to have pre-frailty (odds ratio [OR] = 1.56; 95% confidence interval [CI]: 1.25-1.93; P for trend <0.001) than those in the lowest Q1. A similar positive association was detected for E-DII and pre-frailty. A significant association was found between DII and frailty. Compared with the lowest Q1, the highest Q5 of DTAC was negatively correlated with pre-frailty (OR = 0.66; 95% CI: 0.52-0.84; P for trend <0.001) and frailty (OR = 0.71; 95% CI: 0.50-0.1.03; P for trend <0.001). The DAQS yielded results similar to pre-frailty results (OR = 0.72; 95% CI: 0.58-0.89; P < 0.001). There was no evidence suggesting an association between DAQS and frailty. CONCLUSIONS More proinflammatory diets were linked to higher pre-frailty risk, whereas higher levels of dietary antioxidants were associated with lower pre-frailty and frailty risk among older Chinese adults.
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Affiliation(s)
- Xiaoxia Li
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health of Ningxia Medical University, Yinchuan 750004, China
| | - Qingan Wang
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health of Ningxia Medical University, Yinchuan 750004, China
| | - Tao Ma
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health of Ningxia Medical University, Yinchuan 750004, China
| | - Xiaoyu Chang
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China
| | - Yixuan Xue
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health of Ningxia Medical University, Yinchuan 750004, China
| | - Yadi Zhang
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health of Ningxia Medical University, Yinchuan 750004, China
| | - Wanlu Liu
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health of Ningxia Medical University, Yinchuan 750004, China
| | - Yuhong Zhang
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health of Ningxia Medical University, Yinchuan 750004, China.
| | - Yi Zhao
- School of Public Health of Ningxia Medical University, Yinchuan 750004, China; NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health of Ningxia Medical University, Yinchuan 750004, China.
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Palomo I, Wehinger S, Andrés V, García‐García FJ, Fuentes E. RhoA/rho kinase pathway activation in age-associated endothelial cell dysfunction and thrombosis. J Cell Mol Med 2024; 28:e18153. [PMID: 38568071 PMCID: PMC10989549 DOI: 10.1111/jcmm.18153] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 01/03/2024] [Accepted: 01/09/2024] [Indexed: 04/05/2024] Open
Abstract
The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the age-dependent risk of cardiovascular disease, including endothelial dysfunction, excessive permeability, inflammation, impaired angiogenesis, abnormal vasoconstriction, decreased nitric oxide production and apoptosis. Frailty is a loss of physiological reserve and adaptive capacity with advanced age and is accompanied by a pro-inflammatory and pro-oxidative state that promotes vascular dysfunction and thrombosis. This review summarises the role of the RhoA/Rho kinase signalling pathway in endothelial dysfunction, the acquisition of the pro-thrombotic state and vascular ageing. We also discuss the possible role of RhoA/Rho kinase signalling as a promising therapeutic target for the prevention and treatment of age-related cardiovascular disease.
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Affiliation(s)
- Iván Palomo
- Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Medical Technology School, Thrombosis and Healthy Aging Research CenterUniversidad de TalcaTalcaChile
| | - Sergio Wehinger
- Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Medical Technology School, Thrombosis and Healthy Aging Research CenterUniversidad de TalcaTalcaChile
| | - Vicente Andrés
- Centro Nacional de Investigaciones Cardiovasculares (CNIC)MadridSpain
- Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV)MadridSpain
| | - Francisco J. García‐García
- Department of Geriatric MedicineHospital Universitario de Toledo, Instituto de Investigación de Castilla La Mancha (IDISCAM), CIBERFES (ISCIII)ToledoSpain
| | - Eduardo Fuentes
- Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Medical Technology School, Thrombosis and Healthy Aging Research CenterUniversidad de TalcaTalcaChile
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Mau T, Barnes HN, Blackwell TL, Kramer PA, Bauer SR, Marcinek DJ, Ramos SV, Forman DE, Toledo FGS, Hepple RT, Kritchevsky SB, Cummings SR, Newman AB, Coen PM, Cawthon PM. Lower muscle mitochondrial energetics is associated with greater phenotypic frailty in older women and men: the Study of Muscle, Mobility and Aging. GeroScience 2024; 46:2409-2424. [PMID: 37987886 PMCID: PMC10828481 DOI: 10.1007/s11357-023-01002-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 10/29/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Phenotypic frailty syndrome identifies older adults at greater risk for adverse health outcomes. Despite the critical role of mitochondria in maintaining cellular function, including energy production, the associations between muscle mitochondrial energetics and frailty have not been widely explored in a large, well-phenotyped, older population. METHODS The Study of Muscle, Mobility and Aging (SOMMA) assessed muscle energetics in older adults (N = 879, mean age = 76.3 years, 59.2% women). 31Phosporous magnetic resonance spectroscopy measured maximal production of adenosine triphosphate (ATPmax) in vivo, while ex vivo high-resolution respirometry of permeabilized muscle fibers from the vastus lateralis measured maximal oxygen consumption supported by fatty acids and complex I- and II-linked carbohydrates (e.g., Max OXPHOSCI+CII). Five frailty criteria, shrinking, weakness, exhaustion, slowness, and low activity, were used to classify participants as robust (0, N = 397), intermediate (1-2, N = 410), or frail (≥ 3, N = 66). We estimated the proportional odds ratio (POR) for greater frailty, adjusted for multiple potential confounders. RESULTS One-SD decrements of most respirometry measures (e.g., Max OXPHOSCI+CII, adjusted POR = 1.5, 95%CI [1.2,1.8], p = 0.0001) were significantly associated with greater frailty classification. The associations of ATPmax with frailty were weaker than those between Max OXPHOSCI+CII and frailty. Muscle energetics was most strongly associated with slowness and low physical activity components. CONCLUSIONS Our data suggest that deficits in muscle mitochondrial energetics may be a biological driver of frailty in older adults. On the other hand, we did observe differential relationships between measures of muscle mitochondrial energetics and the individual components of frailty.
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Affiliation(s)
- Theresa Mau
- San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
| | - Haley N Barnes
- San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA
| | - Terri L Blackwell
- San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA
| | - Philip A Kramer
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Scott R Bauer
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
- Department of Medicine and Urology, University of California, San Francisco, CA, USA
- Division of General Internal Medicine, San Francisco VA Healthcare System, San Francisco, CA, USA
| | - David J Marcinek
- Department of Radiology, University of Washington, Seattle, WA, USA
| | - Sofhia V Ramos
- AdventHealth, Translational Research Institute, Orlando, FL, USA
| | - Daniel E Forman
- Department of Medicine-Division of Geriatrics and Cardiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
- Geriatrics Research, Education, and Clinical Care (GRECC), VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
| | - Frederico G S Toledo
- Department of Medicine-Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Russell T Hepple
- Department of Physical Therapy, Department of Physiology and Aging, University of Florida, Gainesville, FL, USA
| | - Stephen B Kritchevsky
- Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Steven R Cummings
- San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Anne B Newman
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Paul M Coen
- AdventHealth, Translational Research Institute, Orlando, FL, USA
| | - Peggy M Cawthon
- San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
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10
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He X, Lin X, He B, Xu H, Suo Z, Zhang H. Association between oxidative balance score and frailty in chronic obstructive pulmonary disease. Heliyon 2024; 10:e25750. [PMID: 38375261 PMCID: PMC10875445 DOI: 10.1016/j.heliyon.2024.e25750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 01/27/2024] [Accepted: 02/01/2024] [Indexed: 02/21/2024] Open
Abstract
Background Oxidative stress is associated with frailty and adverse outcomes in chronic obstructive pulmonary disease (COPD). The oxidative balance score (OBS) assesses oxidative stress from diet and lifestyle, with higher OBS indicating more antioxidants than oxidants. A cross-sectional study was conducted to investigate the potential association between OBS and frailty in US adults with COPD. Methods A total of 1201 COPD subjects from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were assessed for frailty using the Frailty Index. OBS, consisting of 20 dietary and lifestyle factors, was the exposure variable. Weighted multiple logistic regression, subgroup analysis, and restricted cubic spline curves were used to assess the association between OBS and frailty. Results Compared with the lowest OBS reference group (Q1), the adjusted odds ratios (ORs) for the highest quartile group (Q4) for OBS, dietary OBS, and lifestyle OBS were 0.41 (95% CI: 0.19-0.92), 0.37 (95% CI: 0.20-0.71), and 0.41 (95% CI: 0.24-0.71), respectively. All trend p-values were less than 0.05. Subgroup and RCS analyses revealed a negative linear association between OBS and frailty, with a significant reduction in frailty risk observed in women compared to men. Conclusions OBS was negatively associated with frailty in COPD. The higher the OBS, the lower the risk of frailty, especially in women. Identifying at-risk populations with OBS and through antioxidant diet and lifestyle are potential ways to reduce the prevalence of frailty.
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Affiliation(s)
- Xiu He
- Department of Critical Care Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital, Shenzhen, China
| | - Xiaohua Lin
- Department of Critical Care Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital, Shenzhen, China
| | - Bin He
- Department of Critical Care Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital, Shenzhen, China
| | - Hongbo Xu
- Department of Critical Care Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital, Shenzhen, China
| | - Zhijun Suo
- Department of Critical Care Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital, Shenzhen, China
| | - Haigang Zhang
- Department of Critical Care Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital/Shenzhen Nanshan People's Hospital, Shenzhen, China
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11
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Virto N, Río X, Angulo-Garay G, García Molina R, Avendaño Céspedes A, Cortés Zamora EB, Gómez Jiménez E, Alcantud Córcoles R, Rodriguez Mañas L, Costa-Grille A, Matheu A, Marcos-Pérez D, Lazcano U, Vergara I, Arjona L, Saeteros M, Lopez-de-Ipiña D, Coca A, Abizanda Soler P, Sanabria SJ. Development of Continuous Assessment of Muscle Quality and Frailty in Older Patients Using Multiparametric Combinations of Ultrasound and Blood Biomarkers: Protocol for the ECOFRAIL Study. JMIR Res Protoc 2024; 13:e50325. [PMID: 38393761 PMCID: PMC10924264 DOI: 10.2196/50325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/11/2023] [Accepted: 01/02/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Frailty resulting from the loss of muscle quality can potentially be delayed through early detection and physical exercise interventions. There is a demand for cost-effective tools for the objective evaluation of muscle quality, in both cross-sectional and longitudinal assessments. Literature suggests that quantitative analysis of ultrasound data captures morphometric, compositional, and microstructural muscle properties, while biological assays derived from blood samples are associated with functional information. OBJECTIVE This study aims to assess multiparametric combinations of ultrasound and blood-based biomarkers to offer a cross-sectional evaluation of the patient frailty phenotype and to track changes in muscle quality associated with supervised exercise programs. METHODS This prospective observational multicenter study will include patients aged 70 years and older who are capable of providing informed consent. We aim to recruit 100 patients from hospital environments and 100 from primary care facilities. Each patient will undergo at least two examinations (baseline and follow-up), totaling a minimum of 400 examinations. In hospital environments, 50 patients will be measured before/after a 16-week individualized and supervised exercise program, while another 50 patients will be followed up after the same period without intervention. Primary care patients will undergo a 1-year follow-up evaluation. The primary objective is to compare cross-sectional evaluations of physical performance, functional capacity, body composition, and derived scales of sarcopenia and frailty with biomarker combinations obtained from muscle ultrasound and blood-based assays. We will analyze ultrasound raw data obtained with a point-of-care device, along with a set of biomarkers previously associated with frailty, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Additionally, we will examine the sensitivity of these biomarkers to detect short-term muscle quality changes and functional improvement after a supervised exercise intervention compared with usual care. RESULTS At the time of manuscript submission, the enrollment of volunteers is ongoing. Recruitment started on March 1, 2022, and ends on June 30, 2024. CONCLUSIONS The outlined study protocol will integrate portable technologies, using quantitative muscle ultrasound and blood biomarkers, to facilitate an objective cross-sectional assessment of muscle quality in both hospital and primary care settings. The primary objective is to generate data that can be used to explore associations between biomarker combinations and the cross-sectional clinical assessment of frailty and sarcopenia. Additionally, the study aims to investigate musculoskeletal changes following multicomponent physical exercise programs. TRIAL REGISTRATION ClinicalTrials.gov NCT05294757; https://clinicaltrials.gov/ct2/show/NCT05294757. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/50325.
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Affiliation(s)
- Naiara Virto
- Department of Physical Activity and Sport Science, Faculty of Education and Sport, University of Deusto, Bilbao, Spain
| | - Xabier Río
- Department of Physical Activity and Sport Science, Faculty of Education and Sport, University of Deusto, Bilbao, Spain
| | - Garazi Angulo-Garay
- Department of Physical Activity and Sport Science, Faculty of Education and Sport, University of Deusto, Bilbao, Spain
| | - Rafael García Molina
- Department of Geriatrics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
- Center for Biomedical Research Network on Fragility and Healthy Aging (CIBERfes), Instituto de Salud Carlos III, Madrid, Spain
| | - Almudena Avendaño Céspedes
- Department of Geriatrics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
- Center for Biomedical Research Network on Fragility and Healthy Aging (CIBERfes), Instituto de Salud Carlos III, Madrid, Spain
- Facultad de Enfermería de Albacete, Universidad de Castilla-La Mancha, Albacete, Spain
| | - Elisa Belen Cortés Zamora
- Department of Geriatrics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
- Center for Biomedical Research Network on Fragility and Healthy Aging (CIBERfes), Instituto de Salud Carlos III, Madrid, Spain
| | - Elena Gómez Jiménez
- Department of Geriatrics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
| | - Ruben Alcantud Córcoles
- Department of Geriatrics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
- Center for Biomedical Research Network on Fragility and Healthy Aging (CIBERfes), Instituto de Salud Carlos III, Madrid, Spain
| | - Leocadio Rodriguez Mañas
- Center for Biomedical Research Network on Fragility and Healthy Aging (CIBERfes), Instituto de Salud Carlos III, Madrid, Spain
- Geriatrics Department, University Hospital of Getafe, Getafe, Spain
| | | | - Ander Matheu
- Center for Biomedical Research Network on Fragility and Healthy Aging (CIBERfes), Instituto de Salud Carlos III, Madrid, Spain
- Biodonostia, Health Research Institute, Donostia, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Diego Marcos-Pérez
- Department of Geriatrics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
| | - Uxue Lazcano
- Biodonostia, Health Research Institute, Donostia, Spain
| | - Itziar Vergara
- Biodonostia, Health Research Institute, Donostia, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
- Osakidetza, Health Care Department, Research Unit APOSIs, Gipuzkoa, Spain
- Research Network in Chronicity, Primary Care and Health Promotion (RICAPPS), Barakaldo, Spain
| | - Laura Arjona
- Deusto Institute of Technology, University of Deusto, Bilbao, Spain
| | - Morelva Saeteros
- Deusto Institute of Technology, University of Deusto, Bilbao, Spain
| | | | - Aitor Coca
- Department of Physical Activity and Sports Sciences, Faculty of Health Sciences, Euneiz University, Vitoria-Gasteiz, Spain
| | - Pedro Abizanda Soler
- Department of Geriatrics, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
- Center for Biomedical Research Network on Fragility and Healthy Aging (CIBERfes), Instituto de Salud Carlos III, Madrid, Spain
- Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, Albacete, Spain
| | - Sergio J Sanabria
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
- Deusto Institute of Technology, University of Deusto, Bilbao, Spain
- Department of Radiology, Stanford University, Palo Alto, CA, United States
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12
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Huang L, Chen H, Liang M. The Association Between Habitual Tea Consumption and Frailty Transition in Community-Dwelling Older Adults: A Prospective Cohort Study. J Am Med Dir Assoc 2024; 25:259-265.e3. [PMID: 37454694 DOI: 10.1016/j.jamda.2023.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 07/18/2023]
Abstract
OBJECTIVES To investigate the association between habitual tea consumption and transitions between frailty states among older adults in China. DESIGN A prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study. SETTING AND PARTICIPANTS A total of 23,720 older adults aged ≥65 years with complete data regarding frailty status and tea consumption were recruited. METHODS The frequency and consistency of tea consumption were introduced to evaluate levels of tea consumption. The frailty index was used to define frailty status (frail and nonfrail). Frailty transition was classified into remaining nonfrail, improvement, worsening, and remaining frail groups. Logistic regression models were applied. RESULTS The overall frailty prevalence at baseline was 19.1%, being lower among consistent daily tea drinkers (12.5%) and higher among non-tea drinkers (21.9%). Logistic regression analyses showed that the risk of frailty was significantly reduced among consistent daily tea drinkers after adjusting for all confounders [odds ratio (OR), 0.81; 95% CI, 0.67-0.98]. During the 3-year follow-up, improvement in frailty status was more common among consistent daily tea drinkers (50.9%) than non-tea drinkers (40.9%), and this trend was opposite in participants with worsened frailty status (consistent daily tea drinkers: 12.2%) vs non-tea drinkers: 19.2%). Further analysis showed that consistent daily tea drinkers were significantly associated with improvement in frailty status (OR, 3.24; 95% CI, 1.02-10.31) and remaining in a nonfrail state (OR, 1.35; 95% CI, 1.00-1.83). In addition, daily tea consumption was observed to be positively associated with remaining in a nonfrail state and inversely associated with worsened frailty status in men, but not in women. CONCLUSIONS AND IMPLICATIONS Older people consuming tea daily tend to have an improved frailty status in the future. Men with daily tea consumption were less likely to have a worsened frailty status. Advocating for the traditional lifestyle of drinking tea could be a promising way to advance healthy aging for older adults.
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Affiliation(s)
- Lanhui Huang
- Department of Geriatric Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, China
| | - Huihe Chen
- Department of Rehabilitation, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
| | - Min Liang
- Department of Geriatric Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, China.
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13
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Bautmans I, Knoop V, Beyer I, Bruunsgaard H, Molbo D, Mortensen EL, Lund R. The relationship between self-perceived fatigue, muscle endurance, and circulating markers of inflammation in participants of the Copenhagen aging and Midlife Biobank (CAMB). Eur Rev Aging Phys Act 2024; 21:2. [PMID: 38297218 PMCID: PMC10829210 DOI: 10.1186/s11556-024-00336-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 01/14/2024] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Fatigue, low muscle endurance, muscle weakness and low-grade inflammation are strongly related to frailty at higher age. When signs of self-perceived fatigue and low muscle endurance are interrelated with low-grade inflammation at midlife, they might be used as early markers for frailty. This study investigated whether the interrelationships among self-perceived fatigue, muscle endurance and inflammation can be observed at midlife. METHODS A total of 965 participants of the Copenhagen Aging and Midlife Biobank (aged 52 ± 4 years, 536 males, 426 females) were assessed for self-perceived fatigue (20-item multidimensional fatigue inventory), muscle endurance (grip work), circulating markers of inflammation (hsCRP, IL-6, IL-10, TNF-alpha and IFN-γ), daily physical activity (PAS-2), body composition (%body fat assessed by bio-impedance) and self-reported health status. Participants were categorised (correcting for age and gender) according to high fatigue and/or low muscle endurance, differences in inflammatory profile between fatigue categories were assessed by ANCOVA (corrected for PAS-2, %body fat and presence of inflammatory conditions). RESULTS Overall, muscle endurance, fatigue and inflammatory markers were significantly interrelated. Higher levels of hsCRP (p < 0.001), IL-6 (p < 0.001), IL-10 (p = 0.035) and TNF-alpha (p = 0.028) were observed in participants presenting both low muscle endurance and high fatigue. IFN-γ was highest in those with high fatigue but normal muscle endurance (p = 0.015). CONCLUSIONS Middle-aged participants with higher fatigue in combination with low muscle endurance show higher levels of inflammation, independently from physical activity, body fat and inflammatory pathology. The underlying mechanisms should be identified and future studies should also investigate whether these individuals show early signs of reduced physiological reserve capacity, which in later life come to full expression by means of frailty.
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Affiliation(s)
- Ivan Bautmans
- Gerontology department (GERO), Vrije Universiteit Brussel, Laarbeeklaan 103, Brussel, B-1090, Belgium.
- Frailty in Ageing Research Group (FRIA), Vrije Universiteit Brussel, Laarbeeklaan 103, Brussel, B-1090, Belgium.
- Department of Geriatrics, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Brussel, B-1090, Belgium.
- SOMT University of Physiotherapy, Softwareweg 5, Amersfoort, 3821, The Netherlands.
| | - Veerle Knoop
- Gerontology department (GERO), Vrije Universiteit Brussel, Laarbeeklaan 103, Brussel, B-1090, Belgium
- Frailty in Ageing Research Group (FRIA), Vrije Universiteit Brussel, Laarbeeklaan 103, Brussel, B-1090, Belgium
- SOMT University of Physiotherapy, Softwareweg 5, Amersfoort, 3821, The Netherlands
| | - Ingo Beyer
- Gerontology department (GERO), Vrije Universiteit Brussel, Laarbeeklaan 103, Brussel, B-1090, Belgium
- Frailty in Ageing Research Group (FRIA), Vrije Universiteit Brussel, Laarbeeklaan 103, Brussel, B-1090, Belgium
| | - Helle Bruunsgaard
- Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Immunology, Center for Inflammation and Metabolism, National University Hospital, Copenhagen, Denmark
| | - Drude Molbo
- Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Erik Lykke Mortensen
- Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
- Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark
- Institute of Preventive Medicine, Bispebjerg Hospital, Copenhagen, Denmark
| | - Rikke Lund
- Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
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14
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Marcos-Pérez D, Cruces-Salguero S, García-Domínguez E, Araúzo-Bravo MJ, Gómez-Cabrera MC, Viña J, Vergara I, Matheu A. Physical Interventions Restore Physical Frailty and the Expression of CXCL-10 and IL-1β Inflammatory Biomarkers in Old Individuals and Mice. Biomolecules 2024; 14:166. [PMID: 38397403 PMCID: PMC10886745 DOI: 10.3390/biom14020166] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 01/15/2024] [Accepted: 01/17/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Frailty is a geriatric syndrome associated with negative health outcomes that represents a dynamic condition with a potential of reversibility after physical exercise interventions. Typically, inflammatory and senescence markers are increased in frail individuals. However, the impact that physical exercise exerts on inflammatory and senescence biomarkers remains unknown. We assessed the effect of physical intervention in old individuals and mice and determined the expression of inflammatory and senescence markers. METHODS Twelve elderly individuals were enrolled from a primary care setting to a 3-month intervention. Frailty was measured by SPPB and the expression of biomarkers by cytokine array and RT-qPCR. In addition, 12 aged C57BL/6 mice completed an intervention, and inflammation and senescence markers were studied. RESULTS The physical intervention improved the SPPB score, reducing frail and pre-frail individuals. This was correlated with a reduction in several pro-inflammatory biomarkers such as IL-6, CXCL-1, CXCL-10, IL-1β, IL-7, GM-CSF as well as p16INK4a and p21CIP1 senescence markers. Otherwise, the levels of anti-inflammatory biomarker IL-4 were significantly increased. Moreover, the physical intervention in mice also improved their functional capacity and restored the expression of inflammatory (Il-1β, Cxcl-10, Il-6, and Cxcl-1) and senescence (p21Cip1) markers. Additionally, PLSDA and ROC curve analysis revealed CXCL-10 and IL-1β to be the biomarkers of functional improvement in both cohorts. CONCLUSIONS Our results showed that a physical intervention improves physical frailty, and reverses inflammation and senescence biomarkers comprising CXCL-10 and IL-1β.
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Affiliation(s)
- Diego Marcos-Pérez
- Cellular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain; (D.M.-P.); (S.C.-S.)
| | - Sara Cruces-Salguero
- Cellular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain; (D.M.-P.); (S.C.-S.)
| | - Esther García-Domínguez
- Freshage Research Group, Faculty of Medicine, Fundación Investigación Hospital Clínico Universitario/Health Research Institute INCLIVA, University of Valencia, 46010 Valencia, Spain; (E.G.-D.); (M.C.G.-C.); (J.V.)
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERfes), 28029 Madrid, Spain
| | - Marcos J. Araúzo-Bravo
- Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, 20014 San Sebastián, Spain;
- IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain
| | - Mari Carmen Gómez-Cabrera
- Freshage Research Group, Faculty of Medicine, Fundación Investigación Hospital Clínico Universitario/Health Research Institute INCLIVA, University of Valencia, 46010 Valencia, Spain; (E.G.-D.); (M.C.G.-C.); (J.V.)
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERfes), 28029 Madrid, Spain
| | - José Viña
- Freshage Research Group, Faculty of Medicine, Fundación Investigación Hospital Clínico Universitario/Health Research Institute INCLIVA, University of Valencia, 46010 Valencia, Spain; (E.G.-D.); (M.C.G.-C.); (J.V.)
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERfes), 28029 Madrid, Spain
| | - Itziar Vergara
- Primary Care Group, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain;
| | - Ander Matheu
- Cellular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain; (D.M.-P.); (S.C.-S.)
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERfes), 28029 Madrid, Spain
- IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain
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15
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Zeidan RS, McElroy T, Rathor L, Martenson MS, Lin Y, Mankowski RT. Sex differences in frailty among older adults. Exp Gerontol 2023; 184:112333. [PMID: 37993077 DOI: 10.1016/j.exger.2023.112333] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 10/24/2023] [Accepted: 11/14/2023] [Indexed: 11/24/2023]
Abstract
By definition, aging is a natural, gradual and continuous process. On the other hand, frailty reflects the increase in vulnerability to stressors and shortens the time without disease (health span) while longevity refers to the length of life (lifespan). The average life expectancy has significantly increased during the last few decades. A longer lifespan has been accompanied by an increase in frailty and decreased independence in older adults, with major differences existing between men and women. For example, women tend to live longer than men but also experience higher rates of frailty and disability. Sex differences prevent optimization of lifestyle interventions and therapies to effectively prevent frailty. Sex differences in frailty and aging are rooted in a complex interplay between uncontrollable (genetic, epigenetic, physiological), and controllable factors (psychosocial and lifestyle factors). Thus, understanding the underlying causes of sex differences in frailty and aging is essential for developing personalized interventions to promote healthy aging and improve quality of life in older men and women. In this review, we have discussed the key contributors and knowledge gaps related to sex differences in aging and frailty.
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Affiliation(s)
- Rola S Zeidan
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America; Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Taylor McElroy
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America; Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Laxmi Rathor
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Matthew S Martenson
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Yi Lin
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America.
| | - Robert T Mankowski
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, United States of America.
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16
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Wang L, Xie S, Hu X, Li J, He S, Gao J, Wang Z. Social capital, depressive symptomatology, and frailty among older adults in the western areas of China. PLoS One 2023; 18:e0292236. [PMID: 37788268 PMCID: PMC10547179 DOI: 10.1371/journal.pone.0292236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 09/14/2023] [Indexed: 10/05/2023] Open
Abstract
We aimed to explore the relationship between social capital (SC) and frailty, and the mediation role of depressive symptoms in this relationship. A cross-sectional study among 2,591 older adults aged ≥60 years old was conducted from September 2020 to May 2021. SC, depressive symptoms, and frailty were measured using the social capital scale, the 9-item patient health questionnaire, and the FRAIL scale, respectively. The mediation model was tested by Bootstrap PROCESS. After controlling for socio-demographical covariates, the SC was negatively correlated with frailty (r = -0.07, P = 0.001), and depressive symptomatology (r = -0.08, P<0.001); while the depressive symptomatology was positively correlated with frailty (r = 0.33, P<0.001). Logistic regression results showed that SC was associated with a lower risk of frailty (OR = 0.94; 95% CI: 0.92-0.97; P<0.001). Depressive symptomatology partially mediated (explained 36.4% of the total variance) the association between SC and frailty. Those findings suggest that SC may protect older adults from frailty by reducing depressive symptoms. Prevention and intervention implications were also discussed.
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Affiliation(s)
- Liqun Wang
- Department of Epidemiology and Statistics, School of Public Health at Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, China
| | - Shufeng Xie
- General Hospital of Ningxia Medical University, Yinchuan, China
| | - Xue Hu
- Department of Epidemiology and Statistics at School of Public Health of Guangdong Medical University, Dongguan, China
| | - Jiangping Li
- Department of Epidemiology and Statistics, School of Public Health at Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, China
| | - Shulan He
- Department of Epidemiology and Statistics, School of Public Health at Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, China
| | - Junling Gao
- Department of Health Education at School of Public Health, Fudan University, Shanghai, China
| | - Zhizhong Wang
- Department of Epidemiology and Statistics at School of Public Health of Guangdong Medical University, Dongguan, China
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17
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Wang Y, Gao T, Wang B. Application of mesenchymal stem cells for anti-senescence and clinical challenges. Stem Cell Res Ther 2023; 14:260. [PMID: 37726805 PMCID: PMC10510299 DOI: 10.1186/s13287-023-03497-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 09/13/2023] [Indexed: 09/21/2023] Open
Abstract
Senescence is a hot topic nowadays, which shows the accumulation of senescent cells and inflammatory factors, leading to the occurrence of various senescence-related diseases. Although some methods have been identified to partly delay senescence, such as strengthening exercise, restricting diet, and some drugs, these only slow down the process of senescence and cannot fundamentally delay or even reverse senescence. Stem cell-based therapy is expected to be a potential effective way to alleviate or cure senescence-related disorders in the coming future. Mesenchymal stromal cells (MSCs) are the most widely used cell type in treating various diseases due to their potentials of self-replication and multidirectional differentiation, paracrine action, and immunoregulatory effects. Some biological characteristics of MSCs can be well targeted at the pathological features of aging. Therefore, MSC-based therapy is also a promising strategy to combat senescence-related diseases. Here we review the recent progresses of MSC-based therapies in the research of age-related diseases and the challenges in clinical application, proving further insight and reference for broad application prospects of MSCs in effectively combating senesce in the future.
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Affiliation(s)
- Yaping Wang
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People's Republic of China
- Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, People's Republic of China
| | - Tianyun Gao
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People's Republic of China
| | - Bin Wang
- Clinical Stem Cell Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, People's Republic of China.
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18
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Smith JT, Noren Hooten N, Mode NA, Zonderman AB, Ezike N, Kaushal S, Evans MK. Frailty, sex, and poverty are associated with DNA damage and repair in frail, middle-aged urban adults. DNA Repair (Amst) 2023; 129:103530. [PMID: 37437502 PMCID: PMC10807508 DOI: 10.1016/j.dnarep.2023.103530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 04/17/2023] [Accepted: 06/27/2023] [Indexed: 07/14/2023]
Abstract
Frailty is an age-related syndrome characterized by reduced recovery from stressors and increased risks of morbidity and mortality. Although frailty is usually studied in those over 65 years, our previous work showed that frailty is both present and a risk factor for premature mortality in midlife. We identified altered gene expression patterns and biological pathways associated with inflammation in frailty. Evidence suggests DNA oxidation damage related to inflammation accumulates with age, and that DNA repair capacity (DRC) declines with age and age-related conditions. We hypothesized that inter-individual differences in DNA oxidation damage and DRC are associated with frailty status and poverty level. Using the CometChip assay, we assessed baseline single-strand breaks and hydrogen peroxide (H2O2)-induced DNA oxidation damage and DRC in non-frail and frail middle-aged African American and White individuals with household incomes above and below poverty. Analysis of baseline single-strand breaks showed no associations with frailty, poverty, race, or sex. However, we identified an interaction between frailty and poverty in H2O2-induced DNA oxidation damage. We also identified interactions between sex and frailty as well as sex and poverty status with DRC. The social determinant of health, poverty, associates with DRC in men. Baseline DNA damage, H2O2-induced DNA damage as well as DRC were associated with serum cytokine levels. IL-10 levels were inversely associated with baseline DNA damage as well as H2O2-induced DNA damage, DRC was altered by IL-4 levels and sex, and by TNF-α levels in the context of sex and poverty status. This is the first evidence that DRC may be influenced by poverty status at midlife. Our data show that social determinants of health should be considered in examining biological pathways through which disparate age-related health outcomes become manifest.
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Affiliation(s)
- Jessica T Smith
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States
| | - Nicole Noren Hooten
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States
| | - Nicolle A Mode
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States
| | - Alan B Zonderman
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States
| | - Ngozi Ezike
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States
| | - Simran Kaushal
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
| | - Michele K Evans
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States.
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Iparraguirre L, Alberro A, Iñiguez SG, Muñoz-Culla M, Vergara I, Matheu A, Otaegui D. Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals. Immun Ageing 2023; 20:33. [PMID: 37434183 DOI: 10.1186/s12979-023-00356-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 06/16/2023] [Indexed: 07/13/2023]
Abstract
BACKGROUND Frailty is an intermediate and reversible geriatric syndrome that often precedes dependence. Therefore, its identification is essential to prevent dependence. Several molecules have been proposed as biomarkers of frailty, but none of them have reached clinical practice. Recently, circular RNAs have emerged as new non-coding RNAs. Their regulatory role together with their high stability in biofluids makes them good candidates as biomarkers for various processes, but, to date, no study has characterized the expression of circRNA in frailty. RESULTS We studied RNA from leukocytes of 35 frails and 35 robust individuals. After RNA-Sequencing, circRNA detection was performed by CIRI2 and Circexplorer2 and differential expression analysis by DESeq2. Validation was performed by Quantitative-PCR. Linear Discriminant Analysis was performed to determine the best circRNA combination to discriminate frail from robust. In addition, CircRNA candidates were studied in 13 additional elder donors before and after a 3-month physical intervention. We found 89 differentially expressed circRNAs (p-value<0.05, FC>|1.5|) with frailty. Upregulation of hsa_circ_0007817, hsa_circ_0101802 and hsa_circ_0060527 in frail individuals was validated. The combination of hsa_circ_0079284, hsa_circ_0007817 and hsa_circ_0075737 levels showed a great biomarker value with a 95.9% probability of correctly classifying frail and robust individuals. Moreover, hsa_circ_0079284 levels decreased after physical intervention in concordance with an improvement in frailty scores. CONCLUSIONS This work describes for the first time a different expression pattern of circular RNA (circRNAs) between frail and robust individuals. Moreover, the level of some circRNAs is modulated after a physical intervention. These results suggest that they could be used as minimally invasive biomarkers of frailty.
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Affiliation(s)
- Leire Iparraguirre
- Multiple Sclerosis Unit. Biodonostia Health Research Institute, 20014, San Sebastián, Spain
- CIBERNED, MADRID, Spain
| | - Ainhoa Alberro
- Multiple Sclerosis Unit. Biodonostia Health Research Institute, 20014, San Sebastián, Spain
- CIBERNED, MADRID, Spain
| | - Saioa Gs Iñiguez
- Multiple Sclerosis Unit. Biodonostia Health Research Institute, 20014, San Sebastián, Spain
| | - Maider Muñoz-Culla
- Multiple Sclerosis Unit. Biodonostia Health Research Institute, 20014, San Sebastián, Spain
- CIBERNED, MADRID, Spain
- Department of Basic Psychological Processes and Their Development, Euskal Herriko Unibertsitatea (UPV/EHU), 20018, San Sebastián, Spain
| | - Itziar Vergara
- Group of Research in Primary Care. Biodonostia Health Research Institute, 20014, San Sebastián, Spain
- Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), San Sebastián, Spain
| | - Ander Matheu
- Cellular oncology group. Biodonostia Health Research Institute, 20014, San Sebastián, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento (CIBERfes), Carlos III Institute, Madrid, Spain
| | - David Otaegui
- Multiple Sclerosis Unit. Biodonostia Health Research Institute, 20014, San Sebastián, Spain.
- CIBERNED, MADRID, Spain.
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20
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Oei S, Millar CL, Nguyen Lily TN, Mukamal KJ, Kiel DP, Lipsitz LA, Hannan MT, Sahni S. Higher intake of dietary flavonols, specifically dietary quercetin, is associated with lower odds of frailty onset over 12 years of follow-up among adults in the Framingham Heart Study. Am J Clin Nutr 2023; 118:27-33. [PMID: 37061164 PMCID: PMC10447475 DOI: 10.1016/j.ajcnut.2023.04.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 04/03/2023] [Accepted: 04/10/2023] [Indexed: 04/17/2023] Open
Abstract
BACKGROUND Polyphenolic antioxidants derived from plant foods may reduce oxidative stress and frailty, but the effect of the polyphenol subclass of dietary flavonoids and their subclasses on frailty is uncertain. OBJECTIVES To determine the association between dietary flavonoids, their subclasses, quercetin (a specific flavonol), and frailty onset in adults. METHODS This prospective cohort study included individuals from the Framingham Heart Study with no frailty at baseline. Intake of total flavonoids, subclasses of flavonoids (flavonols, flavan-3-ols, flavonones, flavones, anthocyanins, and polymeric flavonoids), and quercetin were estimated via semi-quantitative FFQ along with frailty (Fried phenotype), and covariates at baseline (1998-2001). Frailty was re-evaluated in 2011-2014. Logistic regression estimated OR and 95% CIs for each flavonoid variable and frailty onset. RESULTS Mean age was 58.4 y (SD ± 8.3, n = 1701; 55.5% women). The mean total flavonoid intake was 309 mg/d (SD ± 266). After 12.4 (SD ± 0.8) y, 224 (13.2%) individuals developed frailty. Although total flavonoid intake was not statistically associated with frailty onset (adjusted OR: 1.00; 95% CI: 0.99-1.01), each 10 mg/d of higher flavonol intake was linked with 20% lower odds of frailty onset (OR: 0.80; 95% CI: 0.67-0.96). Other subclasses showed no association (P values range: 0.12-0.99), but every 10 mg/d of higher quercetin intake was associated with 35% lower odds of frailty onset (OR: 0.65; 95% CI: 0.48-0.88). CONCLUSIONS Although no association was observed between total flavonoid intake and frailty onset in adults, a higher intake of flavonols was associated with lower odds of frailty onset, with a particularly strong association for quercetin. This hypothesis-generating study highlights the importance of assessing specific subclasses of flavonoids and the potential of dietary flavonols and quercetin as a strategy to prevent the development of frailty.
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Affiliation(s)
- Steven Oei
- Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Courtney L Millar
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States
| | | | - Kenneth J Mukamal
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Douglas P Kiel
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States
| | - Lewis A Lipsitz
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States
| | - Marian T Hannan
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States
| | - Shivani Sahni
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States.
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21
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Griffiths J, Seesen M, Sirikul W, Siviroj P. Malnutrition, Depression, Poor Sleep Quality, and Difficulty Falling Asleep at Night Are Associated with a Higher Risk of Cognitive Frailty in Older Adults during the COVID-19 Restrictions. Nutrients 2023; 15:2849. [PMID: 37447178 DOI: 10.3390/nu15132849] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 06/18/2023] [Accepted: 06/22/2023] [Indexed: 07/15/2023] Open
Abstract
The COVID-19 restrictions, such as social isolation and disruption of daily routines, can have detrimental effects, including increased stress, anxiety, sleep disturbance, and physical and cognitive decline among older adults. This study aimed to examine the association between nutritional status, depression, sleep quality, falling asleep at night, and cognitive frailty (CF) among older Thai adults during the COVID-19 pandemic. This cross-sectional study included 408 older adults with an average age of 70.54 (5.49) years. CF was determined using Fried's frailty phenotype and the Montreal Cognitive Assessment Basic. The Mini Nutritional Assessment-Short Form, Pittsburgh Sleep Quality Index, and geriatric depression assessment were used for assessment. Multiple logistic regression analysis demonstrated that participants who were malnourished (OR 3.786; 95%CI 1.719-8.335), depressed (OR 5.003; 95%CI 2.399-10.434), had poor sleep quality (OR 1.613; 95%CI 1.041-2.500), and engaged in difficulty falling asleep (OR 1.809; 95%CI 1.022-3.203) had a higher risk of CF compared to those who did not exhibit these factors. Therefore, malnutrition, depression, poor sleep quality, and difficulty falling asleep were identified as risk factors for CF among older adults in Thailand linked to the impact of the COVID-19 pandemic. It is crucial to develop interventions to prevent CF resulting from the mentioned variables.
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Affiliation(s)
- Jiranan Griffiths
- Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Mathuramat Seesen
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Wachiranun Sirikul
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Data Analytics and Knowledge Synthesis for Health Care, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Penprapa Siviroj
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
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22
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Kimble R, Papacosta AO, Lennon LT, Whincup PH, Weyant RJ, Mathers JC, Wannamethee SG, Ramsay SE. The Relationship of Oral Health with Progression of Physical Frailty among Older Adults: A Longitudinal Study Composed of Two Cohorts of Older Adults from the United Kingdom and United States. J Am Med Dir Assoc 2023; 24:468-474.e3. [PMID: 36584971 PMCID: PMC10398566 DOI: 10.1016/j.jamda.2022.11.022] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 11/24/2022] [Accepted: 11/29/2022] [Indexed: 12/29/2022]
Abstract
OBJECTIVE To investigate the prospective associations between oral health and progression of physical frailty in older adults. DESIGN Prospective analysis. SETTING AND PARTICIPANTS Data are from the British Regional Heart Study (BRHS) comprising 2137 men aged 71 to 92 years from 24 British towns and the Health, Aging, and Body Composition (HABC) Study of 3075 men and women aged 70 to 79 years. METHODS Oral health markers included denture use, tooth count, periodontal disease, self-rated oral health, dry mouth, and perceived difficulty eating. Physical frailty progression after ∼8 years follow-up was determined based on 2 scoring tools: the Fried frailty phenotype (for physical frailty) and the Gill index (for severe frailty). Logistic regression models were conducted to examine the associations between oral health markers and progression to frailty and severe frailty, adjusted for sociodemographic, behavioral, and health-related factors. RESULTS After full adjustment, progression to frailty was associated with dentition [per each additional tooth, odds ratio (OR) 0.97; 95% CI: 0.95-1.00], <21 teeth with (OR 1.74; 95% CI: 1.02-2.96) or without denture use (OR 2.45; 95% CI 1.15-5.21), and symptoms of dry mouth (OR ≥1.8; 95% CI ≥ 1.06-3.10) in the BRHS cohort. In the HABC Study, progression to frailty was associated with dry mouth (OR 2.62; 95% CI 1.05-6.55), self-reported difficulty eating (OR 2.12; 95% CI 1.28-3.50) and ≥2 cumulative oral health problems (OR 2.29; 95% CI 1.17-4.50). Progression to severe frailty was associated with edentulism (OR 4.44; 95% CI 1.39-14.15) and <21 teeth without dentures after full adjustment. CONCLUSIONS AND IMPLICATIONS These findings indicate that oral health problems, particularly tooth loss and dry mouth, in older adults are associated with progression to frailty in later life. Additional research is needed to determine if interventions aimed at maintaining (or improving) oral health can contribute to reducing the risk, and worsening, of physical frailty in older adults.
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Affiliation(s)
- Rachel Kimble
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK; Division of Sport and Exercise Science, School of Health and Life Sciences, University of the West of Scotland, Blantyre, UK.
| | - A Olia Papacosta
- Department of Primary Care and Population Health, UCL, London, UK
| | - Lucy T Lennon
- Department of Primary Care and Population Health, UCL, London, UK
| | - Peter H Whincup
- Population Health Research Institute, St George's, University of London, London, UK
| | - Robert J Weyant
- Department of Dental Public Health, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - John C Mathers
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | | | - Sheena E Ramsay
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
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23
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Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases. Signal Transduct Target Ther 2023; 8:116. [PMID: 36918530 PMCID: PMC10015098 DOI: 10.1038/s41392-023-01343-5] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/16/2022] [Accepted: 01/19/2023] [Indexed: 03/16/2023] Open
Abstract
The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition to deteriorated disorders. Rejuvenation refers to giving aged cells or organisms more youthful characteristics through various techniques, such as cellular reprogramming and epigenetic regulation. The great leaps in cellular rejuvenation prove that ageing is not a one-way street, and many rejuvenative interventions have emerged to delay and even reverse the ageing process. Defining the mechanism by which roadblocks and signaling inputs influence complex ageing programs is essential for understanding and developing rejuvenative strategies. Here, we discuss the intrinsic and extrinsic factors that counteract cell rejuvenation, and the targeted cells and core mechanisms involved in this process. Then, we critically summarize the latest advances in state-of-art strategies of cellular rejuvenation. Various rejuvenation methods also provide insights for treating specific ageing-related diseases, including cellular reprogramming, the removal of senescence cells (SCs) and suppression of senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune rejuvenation and heterochronic transplantation, etc. The potential applications of rejuvenation therapy also extend to cancer treatment. Finally, we analyze in detail the therapeutic opportunities and challenges of rejuvenation technology. Deciphering rejuvenation interventions will provide further insights into anti-ageing and ageing-related disease treatment in clinical settings.
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Affiliation(s)
- Shuaifei Ji
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Mingchen Xiong
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Huating Chen
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Yiqiong Liu
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Laixian Zhou
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Yiyue Hong
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Mengyang Wang
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China
| | - Chunming Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macau SAR, China.
| | - Xiaobing Fu
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China.
| | - Xiaoyan Sun
- Research Center for Tissue Repair and Regeneration Affiliated to Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration; Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, P. R. China.
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24
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Soto ME, Pérez-Torres I, Rubio-Ruiz ME, Cano-Martínez A, Manzano-Pech L, Guarner-Lans V. Frailty and the Interactions between Skeletal Muscle, Bone, and Adipose Tissue-Impact on Cardiovascular Disease and Possible Therapeutic Measures. Int J Mol Sci 2023; 24:ijms24054534. [PMID: 36901968 PMCID: PMC10003713 DOI: 10.3390/ijms24054534] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 02/18/2023] [Accepted: 02/24/2023] [Indexed: 03/02/2023] Open
Abstract
Frailty is a global health problem that impacts clinical practice. It is complex, having a physical and a cognitive component, and it is the result of many contributing factors. Frail patients have oxidative stress and elevated proinflammatory cytokines. Frailty impairs many systems and results in a reduced physiological reserve and increased vulnerability to stress. It is related to aging and to cardiovascular diseases (CVD). There are few studies on the genetic factors of frailty, but epigenetic clocks determine age and frailty. In contrast, there is genetic overlap of frailty with cardiovascular disease and its risk factors. Frailty is not yet considered a risk factor for CVD. It is accompanied by a loss and/or poor functioning of muscle mass, which depends on fiber protein content, resulting from the balance between protein breakdown and synthesis. Bone fragility is also implied, and there is a crosstalk between adipocytes, myocytes, and bone. The identification and assessment of frailty is difficult, without there being a standard instrument to identify or treat it. Measures to prevent its progression include exercises, as well as supplementing the diet with vitamin D and K, calcium, and testosterone. In conclusion, more research is needed to better understand frailty and to avoid complications in CVD.
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Affiliation(s)
- María Elena Soto
- Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
| | - Israel Pérez-Torres
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
| | - María Esther Rubio-Ruiz
- Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
| | - Agustina Cano-Martínez
- Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
| | - Linaloe Manzano-Pech
- Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
| | - Verónica Guarner-Lans
- Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
- Correspondence:
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25
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Anwar M, Pradhan R, Dey S, Kumar R. The Role of Sirtuins in Sarcopenia and Frailty. Aging Dis 2023; 14:25-32. [PMID: 36818553 PMCID: PMC9937701 DOI: 10.14336/ad.2022.0622] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 06/22/2022] [Indexed: 11/18/2022] Open
Abstract
The population of older individuals is increasing rapidly, but only a small fraction among them is able to experiences a healthy life. Due to lack of physical exercise and oxidative stress, aging leads to sarcopenia and finally end up with frailty. Sarcopenia is a component of the frailty and described as age related degenerative changes in the skeletal muscle mass, strength and quality. Though the loss of muscle strength and mass gradually seem inevitable during aging, it can be partially prevented or overcome by a deeper insight into the pathogenesis. Sirtuin protein leads to longevity across different organisms ranging from worms to mammals. Expression of sirtuin protein increases during physical exercise and thus strengthens muscle mass. Satellite cells leads to muscle repair in a SIRT1 dependent manner. In addition, SIRT1 improves insulin sensitivity and induces autophagy in the aged mice. The current paper discussed the putative role of sirtuins in sarcopenia and frailty. Moreover, it highlighted the pathways by which sirtuins can inhibit ROS production, inflammation and mitochondrial dysfunctions and therefore confers a protective role against frailty and sarcopenia. The critical role of sirtuins in the sarcopenia and frailty pathogenesis can eventually fuel the development of novel interventions by targeting sirtuins.
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Affiliation(s)
- Masroor Anwar
- Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Rashmita Pradhan
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
| | - Sharmistha Dey
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India,Correspondence should be addressed to: Dr. Rahul Kumar, GITAM Institiute of Sciences, GITAM (Deemed to be) University, Gandhi Nagar, Rushikonda, Andhra Pradesh-53004, India.; Dr. Sharmitha Dey, All India Institute of Medical Sciences, New Delhi-110059, India.
| | - Rahul Kumar
- Department of Biotechnology, GITAM Institute of Sciences, GITAM (Deemed to be) University, Vishakhapatnam, India,Correspondence should be addressed to: Dr. Rahul Kumar, GITAM Institiute of Sciences, GITAM (Deemed to be) University, Gandhi Nagar, Rushikonda, Andhra Pradesh-53004, India.; Dr. Sharmitha Dey, All India Institute of Medical Sciences, New Delhi-110059, India.
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Relationship between Glucose-6-Phosphate Dehydrogenase Deficiency, X-Chromosome Inactivation and Inflammatory Markers. Antioxidants (Basel) 2023; 12:antiox12020334. [PMID: 36829893 PMCID: PMC9952105 DOI: 10.3390/antiox12020334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/21/2023] [Accepted: 01/27/2023] [Indexed: 02/04/2023] Open
Abstract
Recent studies suggest that X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency entails a proinflammatory state that may increase the risk of several disease conditions. However, it is not clear how this relates to the degree of enzyme insufficiency and, in heterozygous females, to skewed inactivation of the X chromosome. This study aimed to (i) investigate the enzyme activity in a cohort of 232 subjects (54.3% females) from Northern Sardinia, Italy, further stratified into three subgroups (G6PD normal, partial deficiency and total deficiency); (ii) measure the levels of some non-specific inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and those derived from cell counts, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR), in relation to the underlying molecular defect and X inactivation. G6PD activity was measured in red blood cells according to G6PD/6PGD ratio, and X-chromosome inactivation was assessed by the HUMARA method. Overall, ESR was increased in males with total deficiency compared with normal males (15.0 ± 7.2 vs. 11.9 ± 6.2, p = 0.002, Tukey's test), albeit not in males with partial deficiency. High-sensitivity CRP was slightly increased in males with total deficiency, compared to males with normal G6PD activity (5.96 ± 3.39 vs. 3.95 ± 2.96, p = 0.048). In females, neither marker showed significant differences across the subgroups. MLR was significantly and progressively increased from normal to totally deficient subjects with intermediate values in partially deficient subjects (0.18, 0.31 and 0.37, ANOVA p = 0.008). The NLR and PLR were not different in the three subgroups. Our findings show that G6PD deficiency may be associated with a proinflammatory profile, especially in elderly females, and worsened by the concomitant asymmetric inactivation of the X chromosome.
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Sun M, Wang L, Wang X, Tong L, Fang J, Wang Y, Yang Y, Li B. Interaction between sleep quality and dietary inflammation on frailty: NHANES 2005-2008. Food Funct 2023; 14:1003-1010. [PMID: 36546877 DOI: 10.1039/d2fo01832b] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Aims: The underlying mechanism of both sleep disorders and frailty is chronic inflammation, which can be reflected by the dietary inflammatory index (DII). Therefore, we aimed to explore the association between sleep quality, frailty, and dietary inflammation. Methods: 9007 participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES) in 2005-2008 were involved in the study. Dietary inflammation was assessed by DII, sleep quality was assessed by the Pittsburgh sleep quality index (PSQI), and frailty was assessed by the 36-item frailty index (FI). Logistic regression, stratified analysis of sub-groups, and forest plots were used in this study. Results: Both pro-inflammatory diet and poor sleep quality were risk factors for frailty. There was an interaction between dietary inflammation and sleep quality (P-interaction = 0.003). Pro-inflammatory diet was associated with increased risk of frailty among the population with poor sleep quality. Compared with the anti-inflammatory diet and good sleep quality group, the OR of frailty was 1.44 (1.21, 1.73) and 2.16 (1.64, 2.80) for the anti-inflammatory diet and poor sleep quality and pro-inflammatory diet and poor sleep quality groups, respectively. Conclusion: There was an interaction between dietary inflammation and sleep quality on frailty. Anti-inflammatory diet may attenuate the detrimental impacts of poor sleep quality on frailty.
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Affiliation(s)
- Mengzi Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Ling Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Xuhan Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Li Tong
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Jiaxin Fang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Yuxiang Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Yixue Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Bo Li
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
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28
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Wu JP. Combined Ketogenic Diet and Walking Exercise Interventions in Community Older Frailty and Skeletal Muscle Sarcopenia. FRAILTY AND SARCOPENIA - RECENT EVIDENCE AND NEW PERSPECTIVES 2022. [DOI: 10.5772/intechopen.101579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2025]
Abstract
The ketogenic diet and walking exercise training interventions are two key public health lifestyle factors. The potential of combined lifestyle factors interventions focused on getting to compliance in diet and exercise. A balanced ketogenic diet and regular exercise interventions is key modifiable factor to the prevention and management of community older frailty and skeletal muscle sarcopenia. Influence health across the lifespan and reduction of the risk of premature death through several biochemistry mechanisms. Community older group’s lifestyle factors interventions contribute identity in their natural living environment. While the older health benefits of walking exercise training interventions strategies are commonly to study, combining ketogenic diet and walking exercise interventions can induce greater benefits in community older groups.
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29
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Mensah E, Ali K, Banya W, Kirkham FA, Mengozzi M, Ghezzi P, Rajkumar C. FRailty and Arterial stiffness - the role of oXidative stress and Inflammation (FRAXI study). Biomark Insights 2022; 17:11772719221130719. [PMID: 36275839 PMCID: PMC9583202 DOI: 10.1177/11772719221130719] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 09/16/2022] [Indexed: 11/08/2022] Open
Abstract
Objective There is an association between frailty and arterial stiffness. However, arterial stiffness does not uniformly correlate with the spectrum of frailty states. Both oxidative stress and inflammaging contribute to vascular ageing. There are no human studies exploring links between arterial stiffness, oxidative stress, inflammaging and frailty. Our objective is to investigate arterial stiffness and inflammaging as predictors of frailty states. Methods An observational longitudinal cohort study will be used to examine the association between arterial stiffness, oxidative stress and inflammation in 50 older adults (⩾70 years) with clinical frailty scores (CFS) ⩽6 over 6 months. All study measurements will be taken at baseline. Frailty assessment will include hand-grip strength, timed-up and go test, mini-mental state examination, geriatric depression scale and sarcopenia using body composition measurements with Tanita®. Arterial stiffness measurements will include carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV) using Complior (Alam Medical, France). CAVI device will measure Cardio-ankle vascular index and ankle brachial index (ABI). Oxidative stress blood markers nitrotyrosine (NT) and 8-hydroxy-2'-deoxyguanosin (8-oxo-dG) and inflammation markers high-sensitive C-reactive protein (hs-CRP) and interlukin-6(IL-6) will be measured at baseline and 6 month along with lipid profile and glycated haemoglobin. Results data analysis plan Descriptive statistics for continuous data using means and standard deviations for normality distributed variables or medians and inter-quartile ranges for skewed variables will be used. Participants will be categorised into CFS 1-3, and CFS 4-6. Categorical data will use frequencies and comparison between groups. Change in frailty between the groups over 6 months will be compared using paired t-test. Simple linear regression will be done between frailty measures, arterial stiffness, inflammation and oxidative stress biomarkers. Significance will be at P < .05. Conclusion This study data will inform a larger, multi-centre study exploring further the interplay between frailty, biomarkers and arterial stiffness parameters.
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Affiliation(s)
- Ekow Mensah
- Brighton and Sussex Clinical Trials
Unit, University Hospitals Sussex NHS Trust, Brighton, UK,Ekow Mensah, Brighton and Sussex Clinical
Trials Unit, University Hospitals Sussex NHS Trust, Audrey Emerton Building,
Eastern Road, Brighton, BN2 5BE, UK.
| | - Khalid Ali
- Brighton and Sussex Clinical Trials
Unit, University Hospitals Sussex NHS Trust, Brighton, UK,Department of Medicine, Brighton and
Sussex Medical School, University of Sussex, Brighton, UK
| | - Winston Banya
- Research Office, Royal Brompton and
Harefield Clinical Group, Guy’s and St. Thomas’ NHS Foundation Trust, London,
UK
| | - Frances Ann Kirkham
- Brighton and Sussex Clinical Trials
Unit, University Hospitals Sussex NHS Trust, Brighton, UK
| | - Manuela Mengozzi
- Department of Medicine, Brighton and
Sussex Medical School, University of Sussex, Brighton, UK
| | | | - Chakravarthi Rajkumar
- Brighton and Sussex Clinical Trials
Unit, University Hospitals Sussex NHS Trust, Brighton, UK,Department of Medicine, Brighton and
Sussex Medical School, University of Sussex, Brighton, UK
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30
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Li S, Cui G, Yin Y, Lv F, Yao Y. Association between tea consumption and frailty among Chinese older adults: A cross-sectional study. Front Nutr 2022; 9:987911. [PMID: 36204378 PMCID: PMC9531025 DOI: 10.3389/fnut.2022.987911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 08/08/2022] [Indexed: 11/23/2022] Open
Abstract
Background Chronic inflammation is considered one of the main mechanisms leading to frailty. It has been demonstrated that tea consumption reduces chronic inflammation. Few epidemiological studies have investigated the association between tea consumption and frailty. Objective This study aimed to analyze the association between tea consumption and frailty in Chinese older adults. Methods Between March and May 2021, we enrolled 2,144 older adults aged ≥60 years in Jinan City, Shandong Province, China, using multi-stage stratified cluster sampling. We assessed tea consumption and frailty in older adults using the Tilburg Frailty Indicator (TFI) and the frequency of tea consumption, respectively. We applied multiple logistic regression analysis to examine the association between tea consumption and frailty, controlling for a set of potential covariates. Results The prevalence of frailty among older Chinese adults was 38.3% (821/2,144). Tea consumption was categorized as daily (30.4%), occasionally (20.9%), and rarely or never (48.7%). As indicated by the fully adjusted model, daily tea consumption was associated with a lower prevalence of frailty (OR = 0.73, 95%CI = 0.57–0.94). However, this association only applied to men, younger older adults aged 60–79 years, rural residents, and regular participants in community activities. In addition, we observed a linear relationship between tea consumption and the prevalence of frailty (P for trend = 0.017). Conclusions Higher tea consumption was associated with a lower prevalence of frailty in older adults, especially those men, older adults aged 60–79, rural residents, and individuals who regularly participated in community activities. Further longitudinal and experimental studies are needed to determine the causation between tea consumption and frailty.
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Affiliation(s)
- Shaojie Li
- School of Public Health, Peking University, Beijing, China
- China Center for Health Development Studies, Peking University, Beijing, China
| | - Guanghui Cui
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
| | - Yongtian Yin
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Faqin Lv
- Ultrasonic Department, The Third Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
- *Correspondence: Faqin Lv
| | - Yao Yao
- China Center for Health Development Studies, Peking University, Beijing, China
- Yao Yao
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31
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Abd.Ghafar MZA, O’Donovan M, Sezgin D, Moloney E, Rodríguez-Laso Á, Liew A, O’Caoimh R. Frailty and diabetes in older adults: Overview of current controversies and challenges in clinical practice. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2022; 3:895313. [PMID: 36992729 PMCID: PMC10012063 DOI: 10.3389/fcdhc.2022.895313] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 07/27/2022] [Indexed: 11/13/2022]
Affiliation(s)
- Mohd Zaquan Arif Abd.Ghafar
- Faculty of Medicine, Universiti Teknologi MARA (Sungai Buloh), Selangor, Malaysia
- Geriatrics Unit, Selayang Hospital, Selangor, Malaysia
- *Correspondence: Mohd Zaquan Arif Abd.Ghafar,
| | - Mark O’Donovan
- Department of Geriatric Medicine, Mercy University Hospital, Cork, Ireland
- Health Research Board Clinical Research Facility, University College Cork, Cork, Ireland
| | - Duygu Sezgin
- School of Nursing and Midwifery, Aras Moyola, National University of Ireland Galway, Galway, Ireland
| | - Elizabeth Moloney
- Department of Geriatric Medicine, Mercy University Hospital, Cork, Ireland
- Health Research Board Clinical Research Facility, University College Cork, Cork, Ireland
| | - Ángel Rodríguez-Laso
- CIBERFES (Área temática de Fragilidad y Envejecimiento Saludable del Centros de Investigación Biomédica en Red), Instituto de Salud Carlos III, Madrid, Spain
| | - Aaron Liew
- Department of Endocrinology, National University of Ireland Galway, Galway, Ireland
| | - Rónán O’Caoimh
- Department of Geriatric Medicine, Mercy University Hospital, Cork, Ireland
- Health Research Board Clinical Research Facility, University College Cork, Cork, Ireland
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32
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Antioxidant Effects of a Polyphenol-Rich Dietary Supplement Incorporating Pinus massoniana Bark Extract in Healthy Older Adults: A Two-Arm, Parallel Group, Randomized Placebo-Controlled Trial. Antioxidants (Basel) 2022; 11:antiox11081560. [PMID: 36009279 PMCID: PMC9405161 DOI: 10.3390/antiox11081560] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 11/18/2022] Open
Abstract
Oxidative stress is a key physiological phenomenon underpinning the ageing process and plays a major developmental role in age-associated chronic diseases. This study investigated the antioxidant effects of a polyphenol-rich dietary supplement containing Pinus massoniana bark extract (PMBE) in healthy older adults. In a double-blinded, placebo-controlled clinical trial, participants were randomised (in a 1:1 ratio) to receive a 50 mL/day dietary supplement containing placebo (0 mg PMBE) or PMBE (1322 mg PMBE) for 12 weeks. The primary outcome was fasting plasma malondialdehyde (MDA) concentrations and secondary outcomes were plasma inflammatory markers. MDA concentrations significantly reduced following PMBE for 6 weeks (−1.19 nmol/mL, 95%CI −1.62, −0.75, p < 0.001) and 12 weeks (−1.35 nmol/mL, 95%CI −1.74, −0.96, p < 0.001) compared to baseline. MDA did not significantly change after the placebo. MDA levels at 6 and 12 weeks were significantly lower following PMBE compared to placebo (p < 0.001). At 12 weeks in the PMBE group, fibrinogen concentrations significantly reduced (−0.25 g/L, 95%CI −0.39, −0.11; p < 0.0001) and interleukin-6 significantly increased compared to placebo (0.30 pg/mL, 95%CI 0.02, 0.59; p < 0.05). PMBE in a polyphenol-rich dietary supplement reduced oxidative stress in healthy older adults. Further studies are warranted to investigate the antioxidant capacity of PMBE in conditions with heightened oxidative stress, such as osteoarthritis, hypertension, type 2 diabetes, or other lifestyle related diseases.
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33
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Frailty in rodents: Models, underlying mechanisms, and management. Ageing Res Rev 2022; 79:101659. [PMID: 35660004 DOI: 10.1016/j.arr.2022.101659] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 04/24/2022] [Accepted: 05/30/2022] [Indexed: 11/22/2022]
Abstract
Frailty is a clinical geriatric syndrome characterized by decreased multisystem function and increased vulnerability to adverse outcomes. Although numerous studies have been conducted on frailty, the underlying mechanisms and management strategies remain unclear. As rodents share homology with humans, they are used extensively as animal models to study human diseases. Rodent frailty models can be classified broadly into the genetic modification and non-genetic modification models, the latter of which include frailty assessment models (based on the Fried frailty phenotype and frailty index methods) and induced frailty models. Such models were developed for use in investigating frailty-related physiological changes at the gene, cellular, molecular, and system levels, including the organ system level. Furthermore, exercise, diet, and medication interventions, in addition to their combinations, could improve frailty status in rodents. Rodent frailty models provide novel and effective tools for frailty research. In the present paper, we review research progress in rodent frailty models, mechanisms, and management, which could facilitate and guide further clinical research on frailty in older adults.
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Umehara T, Kaneguchi A, Yamasaki T, Matsuura A, Kito N, Tanaka H, Yamaoka K. Interactive effects of exercise and sleep on frailty severity in community-dwelling older adults: a cross-sectional study. J Rural Med 2022; 17:21-28. [PMID: 35047098 PMCID: PMC8753256 DOI: 10.2185/jrm.2021-041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 10/02/2021] [Indexed: 01/07/2023] Open
Abstract
Objectives: This study examined the effects of the interaction between
exercise and sleep on frailty severity in community-dwelling older adults. Materials and Methods: This was a cross-sectional study. Data were collected
in July 2019. In total, 2021 adults participated who responded to a questionnaire. Among
them, 672 participants (317 men and 355 women) with valid responses were included in the
analysis. Ordinal logistic regression analysis was performed to examine the association
between frailty severity and the interaction between exercise and sleep. The dependent
variable represents three different levels of frailty. The independent variables included
basic information and interaction between exercise and sleep. Results: The results of ordinal logistic regression analysis (odds ratio
[OR]) showed that the period from the start of exercise (OR=0.96), age (OR=1.00 for
participants in their 60 s, OR=1.65 for those in their 70s, and OR=3.13 for those aged
>80 years), poor subjective health perception (OR=2.12), poor quality of sleep
(OR=1.88), stress (OR=1.62), and exercise–sleep interaction (OR=1.00 based on
good-exercise–good-sleep interaction, OR=3.09 poor-exercise–good-sleep interaction, and
OR=3.50 poor-exercise–poor-sleep interaction) significantly contributed to the model. The
Nagelkerke coefficient of determination adjusted for degrees-of-freedom (R2),
which represents the contribution rate of the regression equation, was 0.334. Conclusions: Our results suggest that a combination of good exercise and
good sleep is needed to prevent frailty progression in community-dwelling older
adults.
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Affiliation(s)
- Takuya Umehara
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Japan
| | - Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Japan
| | - Takahiro Yamasaki
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Japan.,Well-being and Wellness Center, Hiroshima International University, Japan
| | - Akihiro Matsuura
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Japan
| | - Nobuhiro Kito
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Japan.,Well-being and Wellness Center, Hiroshima International University, Japan
| | - Hideki Tanaka
- Well-being and Wellness Center, Hiroshima International University, Japan.,Department of Psychology, Faculty of Health Science, Hiroshima International University, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Japan.,Well-being and Wellness Center, Hiroshima International University, Japan
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35
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Liu M, He P, Zhou C, Zhang Z, Zhang Y, Li H, Liu C, Nie J, Liang M, Qin X. Association of urinary albumin-to-creatinine ratio with incident frailty in older populations. Clin Kidney J 2022; 15:1093-1099. [PMID: 35664283 PMCID: PMC9155239 DOI: 10.1093/ckj/sfac002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Indexed: 11/13/2022] Open
Abstract
Background The longitudinal relationship of albuminuria with incident frailty remains unknown. Therefore we aimed to evaluate the relation of albuminuria with the risk of incident frailty in older adults. Methods A total of 1115 participants ≥65 years of age (average age 80.3 years) who were free of frailty in the Chinese Longitudinal Healthy Longevity Survey were included. The outcome was incident frailty, defined as a frailty index ≥0.25 during follow-up. Cox proportional hazards models were used to assess the association of the urinary albumin:creatinine ratio (UACR) with frailty. Results During a median follow-up duration of 5.3 years, 295 (26.5%) participants developed incident frailty. Overall, the UACR was significantly positively associated with the risk of incident frailty (P for trend = 0.005), with a significantly higher risk of incident frailty in participants in the quartile 4 of UACR {≥13.43 mg/g; hazard ratio [HR] 1.64 [95% confidence interval (CI) 1.13–2.37]} compared with those in quartile 1 (<0.73 mg/g). Consistently, when UACRs were assessed as clinical categories, compared with participants with UACR <10 mg/g, those with UACR ≥30 mg/g had a higher HR of incident frailty [HR 1.61 (95% CI 1.17–2.20)]. Accounting for the competing risk of death also did not substantially change the results. In addition, a stronger positive association between UACR and incident frailty was found in those with a higher high-sensitivity C-reactive protein level (hs-CRP) (P for interaction = 0.045). Conclusion Albuminuria was positively associated with the risk of incident frailty, particularly in those with higher hs-CRP, emphasizing the importance of managing both albuminuria and inflammation for primary prevention of frailty.
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Affiliation(s)
- Mengyi Liu
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Panpan He
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Chun Zhou
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Zhuxian Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Yuanyuan Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Huan Li
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Chengzhang Liu
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Jing Nie
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Min Liang
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
| | - Xianhui Qin
- Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China
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D'Agnelli S, Amodeo G, Franchi S, Verduci B, Baciarello M, Panerai AE, Bignami EG, Sacerdote P. Frailty and pain, human studies and animal models. Ageing Res Rev 2022; 73:101515. [PMID: 34813977 DOI: 10.1016/j.arr.2021.101515] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 11/08/2021] [Accepted: 11/11/2021] [Indexed: 11/01/2022]
Abstract
The hypothesis that pain can predispose to frailty development has been recently investigated in several clinical studies suggesting that frailty and pain may share some mechanisms. Both pain and frailty represent important clinical and social problems and both lack a successful treatment. This circumstance is mainly due to the absence of in-depth knowledge of their pathological mechanisms. Evidence of shared pathways between frailty and pain are preliminary. Indeed, many clinical studies are observational and the impact of pain treatment, and relative pain-relief, on frailty onset and progression has never been investigated. Furthermore, preclinical research on this topic has yet to be performed. Specific researches on the pain-frailty relation are needed. In this narrative review, we will attempt to point out the most relevant findings present in both clinical and preclinical literature on the topic, with particular attention to genetics, epigenetics and inflammation, in order to underline the existing gaps and the potential future interventional strategies. The use of pain and frailty animal models discussed in this review might contribute to research in this area.
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Teixeira-Gomes A, Laffon B, Valdiglesias V, Gostner JM, Felder T, Costa C, Madureira J, Fuchs D, Teixeira JP, Costa S. Exploring Early Detection of Frailty Syndrome in Older Adults: Evaluation of Oxi-Immune Markers, Clinical Parameters and Modifiable Risk Factors. Antioxidants (Basel) 2021; 10:antiox10121975. [PMID: 34943076 PMCID: PMC8750623 DOI: 10.3390/antiox10121975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/22/2021] [Accepted: 12/02/2021] [Indexed: 12/15/2022] Open
Abstract
Ageing is accompanied with a decline in several physiological systems. Frailty is an age-related syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalisation, and death in older adults. The aim of this study was to understand the relationship between frailty syndrome, immune activation, and oxidative stress. Serum concentrations of vitamins A and E were also evaluated, as well as inflammatory biomarkers (CRP and IL-6) and oxidative DNA levels. A group of Portuguese older adults (≥65 years old) was engaged in this study and classified according to Fried’s frailty phenotype. Significant increases in the inflammatory mediators (CRP and IL-6), neopterin levels, kynurenine to tryptophan ratio (Kyn/Trp), and phenylalanine to tyrosine ratio (Phe/Tyr), and significant decreases in Trp and Tyr concentrations were observed in the presence of frailty. IL-6, neopterin, and Kyn/Trp showed potential as predictable biomarkers of frailty syndrome. Several clinical parameters such as nutrition, dependency scales, and polypharmacy were related to frailty and, consequently, may influence the associations observed. Results obtained show a progressive immune activation and production of pro-inflammatory molecules in the presence of frailty, agreeing with the inflammageing model. Future research should include different dimensions of frailty, including psychological, social, biological, and environmental factors.
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Affiliation(s)
- Armanda Teixeira-Gomes
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal; (A.T.-G.); (C.C.); (J.M.); (S.C.)
- Environmental Health Department, National Institute of Health Doutor Ricardo Jorge, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
- School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), Rua das Taipas 135, 4050-600 Porto, Portugal
| | - Blanca Laffon
- Centro de Investigaciones Científicas Avanzadas (CICA), Grupo DICOMOSA, Departamento de Psicología, Facultad de Ciencias de la Educación, Campus Elviña s/n, Universidade da Coruña, 15071 A Coruña, Spain;
- Instituto de Investigación Biomédica de A Coruña (INIBIC), AE CICA-INIBIC. Oza, 15071 A Coruña, Spain;
| | - Vanessa Valdiglesias
- Instituto de Investigación Biomédica de A Coruña (INIBIC), AE CICA-INIBIC. Oza, 15071 A Coruña, Spain;
- Centro de Investigaciones Científicas Avanzadas (CICA), Grupo NanoToxGen, Departamento de Biología, Facultad de Ciencias, Campus A Zapateira s/n, Universidade da Coruña, 15071 A Coruña, Spain
| | - Johanna M. Gostner
- Institute of Medical Biochemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria;
| | - Thomas Felder
- Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria;
| | - Carla Costa
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal; (A.T.-G.); (C.C.); (J.M.); (S.C.)
- Environmental Health Department, National Institute of Health Doutor Ricardo Jorge, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), Rua das Taipas 135, 4050-600 Porto, Portugal
| | - Joana Madureira
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal; (A.T.-G.); (C.C.); (J.M.); (S.C.)
- Environmental Health Department, National Institute of Health Doutor Ricardo Jorge, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), Rua das Taipas 135, 4050-600 Porto, Portugal
| | - Dietmar Fuchs
- Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria;
| | - João Paulo Teixeira
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal; (A.T.-G.); (C.C.); (J.M.); (S.C.)
- Environmental Health Department, National Institute of Health Doutor Ricardo Jorge, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), Rua das Taipas 135, 4050-600 Porto, Portugal
- Correspondence: or
| | - Solange Costa
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas 135, 4050-600 Porto, Portugal; (A.T.-G.); (C.C.); (J.M.); (S.C.)
- Environmental Health Department, National Institute of Health Doutor Ricardo Jorge, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), Rua das Taipas 135, 4050-600 Porto, Portugal
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Alqahtani BA. Association between Physical Frailty and Sleep Quality among Saudi Older Adults: A Community-Based, Cross-Sectional Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:12741. [PMID: 34886467 PMCID: PMC8656802 DOI: 10.3390/ijerph182312741] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/27/2021] [Accepted: 11/29/2021] [Indexed: 01/07/2023]
Abstract
(1) Background: Prevalence of poor sleep quality and its association with frailty status among the aging population of Saudi Arabia has not been studied. Therefore, the main objective of the current study was to estimate the prevalence of poor sleep quality and investigate the association between poor sleep quality and frailty in Saudi older adults; (2) Methods: A total of 270 (mean age 69.9 ± 6.2) older adults from the Riyadh region were involved in the study. To measure sleep quality, the Arabic version of the Pittsburgh Sleep Quality Index (PSQI) was used. The Fried's frailty index was utilized to assess frailty. Using multiple logistic regression models, the association between sleep quality and frailty status was evaluated using the Odds Ratio and confidence intervals (CI 95%); (3) Results: The pre-frailty and frailty status were prevalent among older adults who had poor sleep quality, 37% and 37.6% (p < 0.001), retrospectively. Poor sleep quality (PSQI > 5) was independently associated with both frailty (OR = 2.13) and prefrailty groups (OR = 1.67); (4) Conclusions: our study demonstrated a significant association between frailty and poor sleep quality. However, a longitudinal future study needs to be established to confirm this association and establish the causality relationship.
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Affiliation(s)
- Bader A Alqahtani
- Department of Health and Rehabilitation Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
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Zhao J, Qu W, Zhou X, Guo Y, Zhang Y, Wu L, Yu Z, Huang H, Luo X. Sleep Quality Mediates the Association Between Cerebral Small Vessel Disease Burden and Frailty: A Community-Based Study. Front Aging Neurosci 2021; 13:751369. [PMID: 34744691 PMCID: PMC8564177 DOI: 10.3389/fnagi.2021.751369] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Accepted: 09/30/2021] [Indexed: 02/03/2023] Open
Abstract
Background: Physical frailty is a common problem among older adults which usually leads to adverse health outcomes. The imaging markers of cerebral small vessel disease (CSVD) are associated with frailty, but the underlying mechanisms remain unclear. The present study aimed to investigate the mediating role of sleep quality in the relationship between CSVD burden and frailty. Methods: We performed a cross-sectional study and enrolled community residents. Frailty and sleep quality were measured using the Fried frailty phenotype and the Pittsburgh Sleep Quality Index (PSQI), respectively. A multivariate linear regression analysis and a Bootstrap analysis were performed to examine the association among the key variables and the mediating role of sleep quality. Results: Of the 726 participants (mean age: 65.5 ± 6.5 years, 59.8% female), the numbers (percentages) of the frail, prefrail, and robust residents were 49 (6.7%), 310 (42.7%), and 367 (50.6%), respectively. After adjusting for covariates, the CSVD burden and PSQI score were significantly associated with the frailty score. In addition, sleep quality played a partial mediating role in the association between CSVD burden and physical frailty. The mediating effect was 21.9%. Conclusion: The present study suggests that sleep quality is a mediator of this association between CSVD and frailty in community-dwelling older adults. Improving sleep quality might be helpful to mitigate the risk of frailty in CSVD patients.
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Affiliation(s)
- Jing Zhao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wensheng Qu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xirui Zhou
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yinping Guo
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi Zhang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lingshan Wu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiyuan Yu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hao Huang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Luo
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Cole JA, Kehmeier MN, Bedell BR, Krishna Kumaran S, Henson GD, Walker AE. Sex Differences in the Relation Between Frailty and Endothelial Dysfunction in Old Mice. J Gerontol A Biol Sci Med Sci 2021; 77:416-423. [PMID: 34664649 DOI: 10.1093/gerona/glab317] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Indexed: 11/14/2022] Open
Abstract
Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.
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Affiliation(s)
- Jazmin A Cole
- Department of Human Physiology, University of Oregon, Eugene, Oregon
| | | | - Bradley R Bedell
- Department of Human Physiology, University of Oregon, Eugene, Oregon
| | | | - Grant D Henson
- Department of Human Physiology, University of Oregon, Eugene, Oregon
| | - Ashley E Walker
- Department of Human Physiology, University of Oregon, Eugene, Oregon
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Dawidowski B, Górniak A, Podwalski P, Lebiecka Z, Misiak B, Samochowiec J. The Role of Cytokines in the Pathogenesis of Schizophrenia. J Clin Med 2021; 10:jcm10173849. [PMID: 34501305 PMCID: PMC8432006 DOI: 10.3390/jcm10173849] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 02/07/2023] Open
Abstract
Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. The available literature reports both elevated levels of proinflammatory as well as reduced levels of anti-inflammatory cytokines, and their effects on clinical status and neuroimaging changes. There is evidence of at least a partial genetic basis for the association between cytokine alterations and schizophrenia. Two other factors implicated in its development include early childhood trauma and disturbances in the gut microbiome. Moreover, its various subtypes, characterized by individual symptom severity and course, such as deficit schizophrenia, seem to differ in terms of changes in peripheral cytokine levels. While the use of a systematic review methodology could be difficult due to the breadth and diversity of the issues covered in this review, the applied narrative approach allows for a more holistic presentation. The aim of this narrative review was to present up-to-date evidence on cytokine dysregulation in schizophrenia, its effect on the psychopathological presentation, and links with antipsychotic medication. We also attempted to summarize its postulated underpinnings, including early childhood trauma and gut microbiome disturbances, and propose trait and state markers of schizophrenia.
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Affiliation(s)
- Bartosz Dawidowski
- Department of Psychiatry, Pomeranian Medical University, 71-460 Szczecin, Poland; (B.D.); (A.G.); (J.S.)
| | - Adrianna Górniak
- Department of Psychiatry, Pomeranian Medical University, 71-460 Szczecin, Poland; (B.D.); (A.G.); (J.S.)
| | - Piotr Podwalski
- Department of Psychiatry, Pomeranian Medical University, 71-460 Szczecin, Poland; (B.D.); (A.G.); (J.S.)
- Correspondence: ; Tel.: +48-510-091-466
| | - Zofia Lebiecka
- Department of Health Psychology, Pomeranian Medical University, 71-210 Szczecin, Poland;
| | - Błażej Misiak
- Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Medical University, 50-367 Wroclaw, Poland;
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University, 71-460 Szczecin, Poland; (B.D.); (A.G.); (J.S.)
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Aleksandrova K, Koelman L, Rodrigues CE. Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies. Redox Biol 2021; 42:101869. [PMID: 33541846 PMCID: PMC8113044 DOI: 10.1016/j.redox.2021.101869] [Citation(s) in RCA: 237] [Impact Index Per Article: 59.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/07/2021] [Accepted: 01/12/2021] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION Oxidative stress and inflammation are known to play a critical role in ageing and chronic disease development and could therefore represent important targets for developing dietary strategies for disease prevention. We aimed to systematically review the results from observational studies and intervention trials published in the last 5 years on the associations between dietary patterns and biomarkers of oxidative stress and inflammation. METHODS A systematic search of the PubMed, MEDLINE and Web of Science (January 2015 to October 2020) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality of selected studies was evaluated based on the NUTRIGRADE and BIOCROSS assessment tools. RESULTS In total, 29 studies among which 16 observational studies and 13 intervention studies were found eligible for review. Overall, results indicated an inverse association between plant-based diets - the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diet - and oxidative stress and proinflammatory biomarkers. In observational studies, inverse associations were further revealed for the vegetarian diet, the USDA Healthy Eating Index (HEI) - based diet and the paleolithic diet, whereas a positive association was seen for western and fast food diets. Quality assessment suggested that majority of dietary intervention studies (n = 12) were of low to moderate quality. CONCLUSIONS This study provides evidence that the plant-based dietary patterns are associated with lowered levels of oxidative stress and inflammation and may provide valid means for chronic disease prevention. Future large-scale intervention trials using validated biomarkers are warranted to confirm these findings.
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Affiliation(s)
- Krasimira Aleksandrova
- Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany; Department Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Germany; Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany.
| | - Liselot Koelman
- Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
| | - Caue Egea Rodrigues
- Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany; Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany
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Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice. Nutrients 2021; 13:nu13041177. [PMID: 33918334 PMCID: PMC8066446 DOI: 10.3390/nu13041177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 11/21/2022] Open
Abstract
Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.
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Zhu Y, Ge J, Huang C, Liu H, Jiang H. Application of mesenchymal stem cell therapy for aging frailty: from mechanisms to therapeutics. Theranostics 2021; 11:5675-5685. [PMID: 33897874 PMCID: PMC8058725 DOI: 10.7150/thno.46436] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 03/15/2021] [Indexed: 12/20/2022] Open
Abstract
Aging frailty is a complex geriatric syndrome that becomes more prevalent with advancing age. It constitutes a major health problem due to frequent adverse outcomes. Frailty is characterized by disruption of physiological homeostasis and progressive decline of health status. Multiple factors contribute to development of frailty with advancing age, including genome instability, DNA damage, epigenetic alternations, stem cell exhaustion, among others. These interrelated factors comprehensively result in loss of tissue homeostasis and diminished reserve capacity in frailty. Therefore, the aged organism gradually represents symptoms of frailty with decline in physiological functions of organs. Notably, the brain, cardiovascular system, skeletal muscle, and endocrine system are intrinsically interrelated to frailty. The patients with frailty may display the diminished reserves capacity of organ systems. Due to the complex pathophysiology, no specific treatments have been approved for prevention of this syndrome. At such, effective strategies for intervening in pathogenic process to improve health status of frail patients are highly needed. Recent progress in cell-based therapy has greatly contributed to the amelioration of degenerative diseases related to age. Mesenchymal stem cells (MSCs) can exert regenerative effects and possess anti-inflammatory properties. Transplantation of MSCs represents as a promising therapeutic strategy to address the pathophysiologic problems of frail syndrome. Currently, MSC therapy have undergone the phase I and II trials in human subjects that have endorsed the safety and efficacy of MSCs for aging frailty. However, despite these positive results, caution is still needed with regard to potential to form tumors, and further large-scale studies are warranted to confirm the therapeutic efficacy of MSC therapy.
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Benchside to the bedside of frailty and cardiovascular aging: Main shared cellular and molecular mechanisms. Exp Gerontol 2021; 148:111302. [PMID: 33675900 DOI: 10.1016/j.exger.2021.111302] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/13/2021] [Accepted: 03/01/2021] [Indexed: 12/14/2022]
Abstract
Due to the impact that frailty and cardiac aging have on society and health systems, the mechanisms surrounding these conditions must be known. If the frailty and cardiovascular complications are due to numerous controllable factors or not, different strategies must be considered to improve the elderly patient's prognosis and improve their quality of life. This review aimed to investigate the main shared mechanisms of cardiac aging and frailty. MEDLINE-PubMed, Cohrane and EMBASE databases were searched to perform this review. The mesh-terms used for this search was frailty, cardiovascular disease, cardiovascular aging, or heart failure (HF). Frailty frequently coexists with heart conditions since they share predisposing pathophysiological alterations, the aging process, and elevated comorbidity burden, contributing to fast functional decline and sarcopenia. Mitochondrial dysfunctions and decreased protein synthesis lead to protein degradation, denervation, atrophy, impairment in the fatty acid oxidation, resulting in cardiomyopathy. The homeostasis of muscle metabolism deteriorates with aging, leading to a reduction in muscle quality and quantity. The installation of a low-grade and chronic inflammatory process adds to an impairment in glucose, protein and lipid metabolism, endothelial dysfunction, cardiovascular conditions, sarcopenia, and HF. The exacerbated rise in inflammatory biomarkers and impaired insulin resistance leads to worsening of the patient's general condition. The good news is that frailty is a dynamic syndrome, fluctuating between different states of seriousness but still has potential for reversibility based on physical activity, cognitive training, nutrition intervention, and a plethora of other approaches that can be performed by a multi-disciplinary team.
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Yao SM, Zheng PP, Wan YH, Dong W, Miao GB, Wang H, Yang JF. Adding high-sensitivity C-reactive protein to frailty assessment to predict mortality and cardiovascular events in elderly inpatients with cardiovascular disease. Exp Gerontol 2021; 146:111235. [PMID: 33453322 DOI: 10.1016/j.exger.2021.111235] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 12/14/2020] [Accepted: 01/04/2021] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Chronic inflammation is associated with major adverse cardiovascular events (MACEs), mortality, and frailty. Our aim was to add high-sensitivity C-reactive protein (hsCRP) to the frailty assessment to predict its association with prognosis of older adults with cardiovascular disease (CVD). METHODS A comprehensive geriatric assessment was conducted at baseline in 720 in-patients aged ≥65 years with CVD. We divided the population into frailty and non-frailty groups according to the Fried phenotype, and hsCRP was further combined with frailty to stratify all patients into c-frailty and non-c-frailty groups. Predictive validity was tested using Cox proportional hazards regression model analysis and the discriminative ability was evaluated by receiver operating characteristic (ROC) curves. RESULTS Of all the subjects enrolled, 51.0% were male and the mean age was 75.32 ± 6.52 years. The all-cause death and MACE rate was 6.4% at the 1-year follow-up. Frailty and c-frailty were independent predictors of all-cause death and MACE (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.35-4.83, p = 0.004; HR: 3.67, 95% CI: 1.83-7.39, p < 0.001). Adding hsCRP to the frailty model resulted in a significant increase in the area under the ROC curve from 0.74 (95% CI: 0.70-0.77) to 0.77 (95% CI: 0.71-0.84) (p = 0.0132) and a net reclassification index of 7.9% (95% CI: 1.96%-12.56%, p = 0.012). CONCLUSION Adding hsCRP to the frailty assessment is helpful to identify a subgroup of older CVD patients with a higher risk of death and MACE over a period of 1 year. TRIAL REGISTRATION ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.
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Affiliation(s)
- Si-Min Yao
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1, DaHua Road, Dong Dan, Beijing 100730, PR China; Peking University Fifth School of Clinical Medicine, No. 1, DaHua Road, Dong Dan, Beijing 100730, PR China
| | - Pei-Pei Zheng
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1, DaHua Road, Dong Dan, Beijing 100730, PR China; Peking University Fifth School of Clinical Medicine, No. 1, DaHua Road, Dong Dan, Beijing 100730, PR China
| | - Yu-Hao Wan
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1, DaHua Road, Dong Dan, Beijing 100730, PR China; Peking University Fifth School of Clinical Medicine, No. 1, DaHua Road, Dong Dan, Beijing 100730, PR China
| | - Wei Dong
- Department of Cardiology, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100039, PR China
| | - Guo-Bin Miao
- Department of Cardiology, Beijing Tsinghua Changgung Hospital, No. 168, Litang Road, Changping District, Beijing 102218, PR China
| | - Hua Wang
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1, DaHua Road, Dong Dan, Beijing 100730, PR China.
| | - Jie-Fu Yang
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1, DaHua Road, Dong Dan, Beijing 100730, PR China
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Shih AC, Chen LH, Tsai CC, Chen JY. Correlation between Sleep Quality and Frailty Status among Middle-Aged and Older Taiwanese People: A Community-Based, Cross-Sectional Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17249457. [PMID: 33348703 PMCID: PMC7766620 DOI: 10.3390/ijerph17249457] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 12/14/2020] [Accepted: 12/15/2020] [Indexed: 12/12/2022]
Abstract
Poor sleep quality and frailty are common problems among aged people. However, the association between sleep quality and frailty in middle-aged and older people is seldom discussed in Asia, especially in Taiwan. This study investigated this association hopefully to provide pertinent knowledge for the prevention of frailty. We conducted a cross-sectional study and enrolled 828 subjects, 237 male and 591 female, aged 50–85 years old, from a community in Northern Taiwan. Poor sleep quality was defined as the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) > 5. Prefrailty and frailty were defined as fulfillment of one or two and three, respectively, of five phenotypic criteria: exhaustion, weakness, slowness, weight loss, and low physical activity. Our univariate analysis showed that the incidence of prefrailty/frailty in the group of poor sleep quality was higher than that in the group of CPSQI ≤ 5 (p < 0.001). Further multiple logistic regression analysis revealed that poor sleep quality was an independent factor for prefrailty and frailty status (odds ratio = 1.95, 95% confidence interval = 1.38–2.77), after adjustment for confounding factors. We concluded that poor sleep quality is independently associated with prefrailty and frailty status in our study population.
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Affiliation(s)
- An-Chen Shih
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan;
| | - Lee-Hwa Chen
- Department of Athletic Training and Health, National Taiwan Sport University, Taoyuan 333, Taiwan; (L.-H.C.); (C.-C.T.)
| | - Chin-Chueh Tsai
- Department of Athletic Training and Health, National Taiwan Sport University, Taoyuan 333, Taiwan; (L.-H.C.); (C.-C.T.)
| | - Jau-Yuan Chen
- Department of Family Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan;
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Correspondence: ; Tel.: +886-975362672
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Kawano T, Naito J, Nishioka M, Nishida N, Takahashi M, Kashiwagi S, Sugino T, Watanabe Y. Effect of Food Containing Paramylon Derived from Euglena gracilis EOD-1 on Fatigue in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial. Nutrients 2020; 12:nu12103098. [PMID: 33053626 PMCID: PMC7601521 DOI: 10.3390/nu12103098] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 10/08/2020] [Accepted: 10/08/2020] [Indexed: 12/16/2022] Open
Abstract
Euglena gracilis EOD-1, a kind of microalgae, is known to contain a high proportion of paramylon, a type of β-1,3-glucan. Paramylon derived from E. gracilis EOD-1 is presumed to suppress cellular oxidative injury and expected to reduce fatigue and fatigue sensation. Therefore, we aimed to examine whether food containing paramylon derived from E. gracilis EOD-1 (EOD-1PM) ingestion reduced fatigue and fatigue sensation in healthy adults. We conducted a randomized, double-blind, placebo-controlled, parallel-group comparison study in 66 healthy men and women who ingested a placebo or EOD-1PM daily for 4 weeks (daily life fatigue). Furthermore, at the examination days of 0 and 4 weeks, tolerance to fatigue load was evaluated using mental tasks (task-induced fatigue). We evaluated fatigue sensation using the Visual Analogue Scale, the work efficiency of the advanced trail making test and measured serum antioxidant markers. The EOD-1PM group showed significantly lower levels of physical and mental fatigue sensations and higher levels of work efficiency as well as serum biological antioxidant potential levels than the placebo group. These results indicate that EOD-1PM ingestion reduced fatigue and fatigue sensation, which may be due to an increase in antioxidant potential and maintenance of selective attention during work.
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Affiliation(s)
- Takanori Kawano
- Kobelco Eco-Solutions Co., Ltd., Kobe, Hyogo 651-2241, Japan; (J.N.); (M.N.); (N.N.); (M.T.)
- Correspondence: (T.K.); (Y.W.); Tel.: +81-78-992-6957 (T.K.); +81-78-304-7100 (Y.W.)
| | - Junko Naito
- Kobelco Eco-Solutions Co., Ltd., Kobe, Hyogo 651-2241, Japan; (J.N.); (M.N.); (N.N.); (M.T.)
| | - Machiko Nishioka
- Kobelco Eco-Solutions Co., Ltd., Kobe, Hyogo 651-2241, Japan; (J.N.); (M.N.); (N.N.); (M.T.)
| | - Norihisa Nishida
- Kobelco Eco-Solutions Co., Ltd., Kobe, Hyogo 651-2241, Japan; (J.N.); (M.N.); (N.N.); (M.T.)
| | - Madoka Takahashi
- Kobelco Eco-Solutions Co., Ltd., Kobe, Hyogo 651-2241, Japan; (J.N.); (M.N.); (N.N.); (M.T.)
| | | | - Tomohiro Sugino
- Soiken. Inc., Toyonaka, Osaka 560-0082, Japan; (S.K.); (T.S.)
| | - Yasuyoshi Watanabe
- RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
- Correspondence: (T.K.); (Y.W.); Tel.: +81-78-992-6957 (T.K.); +81-78-304-7100 (Y.W.)
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Bossù P, Toppi E, Sterbini V, Spalletta G. Implication of Aging Related Chronic Neuroinflammation on COVID-19 Pandemic. J Pers Med 2020; 10:E102. [PMID: 32858874 PMCID: PMC7563730 DOI: 10.3390/jpm10030102] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 08/21/2020] [Accepted: 08/24/2020] [Indexed: 02/07/2023] Open
Abstract
SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a narrative review on selected studies targeting aging-related chronic neuroinflammation in the COVID-19 pandemic. A hyperactivation of the innate immune system with elevated levels of pro-inflammatory cytokines occurs during severe COVID-19, pointing to an important role of the innate immune dysregulation in the disease outcome. Aging is characterized by a general condition of low-grade inflammation, also connected to chronic inflammation of the brain (neuroinflammation), which is involved in frailty syndrome and contributes to several age-associated diseases, including neurodegenerative and neuropsychiatric disorders. Since neuroinflammation can be induced or worsened by the virus infection itself, as well as by stressful conditions like those linked to the recent pandemic, the role of neuroinflammatory mechanisms could be central in a vicious circle leading to an increase in the mortality risk in aged COVID-19 patients. Furthermore, triggered neuroinflammatory pathways and consequent neurodegenerative and neuropsychiatric conditions might be potential long-term complications of COVID-19. In order to provide insights to help clinicians in identifying patients who progress to a more severe case of the disease, this review underlines the potential implications of aging-related neuroinflammation in COVID-19 pandemic.
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Affiliation(s)
- Paola Bossù
- Experimental Neuropsycho-Biology Lab, Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Via del Fosso d Fiorano 64, 00143 Rome, Italy; (E.T.); (V.S.)
| | - Elisa Toppi
- Experimental Neuropsycho-Biology Lab, Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Via del Fosso d Fiorano 64, 00143 Rome, Italy; (E.T.); (V.S.)
| | - Valentina Sterbini
- Experimental Neuropsycho-Biology Lab, Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Via del Fosso d Fiorano 64, 00143 Rome, Italy; (E.T.); (V.S.)
| | - Gianfranco Spalletta
- Neuropsychiatry Lab, Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Via Adeatina 306, 00179 Rome, Italy;
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