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Conrad MB, Leatherwood JL, Paris BL, George JM, Martinez RE, Vergara-Hernandez FB, Nielsen BD, Colbath AC, Arnold CE, Glass KG, Welsh TH, Bradbery AN. Effects of clodronate disodium on endocrine regulators of calcium in yearling horses. J Anim Sci 2025; 103:skaf132. [PMID: 40259552 PMCID: PMC12124253 DOI: 10.1093/jas/skaf132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 04/17/2025] [Indexed: 04/23/2025] Open
Abstract
Extra-label bisphosphonate (BP) use in juvenile horses is anecdotally reported, primarily for analgesic effects, despite the limited scientific understanding of biologic impacts on skeletally immature horses undergoing exercise. The objective of this study was to determine the effects of clodronate disodium (CD), a form of BP, on endocrine regulators of calcium. Thus, 32 yearling Quarter Horses were stratified by age (500 ± 13 d), body weight (BW; 336 ± 26 kg), sex (n = 16 geldings, n = 16 fillies), and initial bone optical density into 1 of 4 treatment groups for a 168-d trial. The experimental period was divided into 2 exercise phases to model industry standards. Investigators were blinded to treatment, and all horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW CD (OSPHOS) or saline (placebo) on days 0, 42, 84, and 126. Treatments consisted of control (CON; n = 8), 1-dose (1X; n = 8; day 84), 2-dose (2X; n = 8; day 0, 84), and 4-dose groups (4X; n = 8; days 0, 42, 84, 126). Serum samples were collected, and physical measurements were recorded including BW, wither height, hip height, body length, and heart girth circumference (HG) every 42 d, prior to treatment administration. Serum samples were analyzed for growth hormone (GH), calcitonin, parathyroid hormone (PTH), and ionized calcium (Ca2+). Data were analyzed using MIXED and CORR procedures of SAS. All physical measurements increased over time (P ≤ 0.01) but were not affected by treatment (P ≥ 0.62). Similarly, there was no effect of treatment for GH (P = 0.44), but concentrations tended to decrease over time (P = 0.09). A treatment × day interaction was observed for PTH (P = 0.05) where concentrations increased following a second CD dose. Specifically, concentrations increased on day 84 in 4X and on day 126 in 2X following the second treatment with CD whereas 1X and CON remained unchanged. Despite the increase in PTH, there was no effect on calcitonin (P ≥ 0.33). Ionized calcium concentrations decreased over time (P < 0.01) with no effect of treatment (P = 0.26). Parathyroid hormone was negatively correlated with serum Ca2+ (r = -0.28, P < 0.01), whereas calcitonin was not correlated with serum Ca2+ (r = 0.06, P = 0.48) nor PTH (r = -0.13, P = 0.12). According to these results, CD has no effect on growth morphometrics, but its use transiently increases PTH concentrations after 2 doses.
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Affiliation(s)
- Matthew B Conrad
- Department of Animal and Range Sciences, Montana State University, Bozeman, MT 59717, USA
| | - Jessica L Leatherwood
- Department of Animal Science, Tarleton State University, Stephenville, TX 76402, USA
- Department of Animal Science, Texas A&M AgriLife Research and Texas A&M University, College Station, TX 77843, USA
| | - Brittany L Paris
- Department of Animal Science, Texas A&M AgriLife Research and Texas A&M University, College Station, TX 77843, USA
| | - James M George
- Department of Animal Science, Tarleton State University, Stephenville, TX 76402, USA
| | - Rafael E Martinez
- Department of Animal Science, Tarleton State University, Stephenville, TX 76402, USA
- Department of Animal Science, Texas A&M AgriLife Research and Texas A&M University, College Station, TX 77843, USA
| | - Fernando B Vergara-Hernandez
- Escuela de Medicina Veterinaria, Facultad de Recursos Naturales y Medicina Veterinaria, Universidad Santo Tomás, Viña del Mar, Chile
| | - Brian D Nielsen
- Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA
| | - Aimee C Colbath
- Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Carolyn E Arnold
- School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX 77843, USA
| | - Kati G Glass
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX 77843, USA
| | - Thomas H Welsh
- Department of Animal Science, Texas A&M AgriLife Research and Texas A&M University, College Station, TX 77843, USA
| | - Amanda N Bradbery
- Department of Animal and Range Sciences, Montana State University, Bozeman, MT 59717, USA
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List EO, Basu R, Berryman DE, Duran-Ortiz S, Martos-Moreno GÁ, Kopchick JJ. Common and Uncommon Mouse Models of Growth Hormone Deficiency. Endocr Rev 2024; 45:818-842. [PMID: 38853618 PMCID: PMC12102728 DOI: 10.1210/endrev/bnae017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 04/22/2024] [Accepted: 05/31/2024] [Indexed: 06/11/2024]
Abstract
Mouse models of growth hormone deficiency (GHD) have provided important tools for uncovering the various actions of GH. Nearly 100 years of research using these mouse lines has greatly enhanced our knowledge of the GH/IGF-1 axis. Some of the shared phenotypes of the 5 "common" mouse models of GHD include reduced body size, delayed sexual maturation, decreased fertility, reduced muscle mass, increased adiposity, and enhanced insulin sensitivity. Since these common mouse lines outlive their normal-sized littermates-and have protection from age-associated disease-they have become important fixtures in the aging field. On the other hand, the 12 "uncommon" mouse models of GHD described herein have tremendously divergent health outcomes ranging from beneficial aging phenotypes (similar to those described for the common models) to extremely detrimental features (such as improper development of the central nervous system, numerous sensory organ defects, and embryonic lethality). Moreover, advancements in next-generation sequencing technologies have led to the identification of an expanding array of genes that are recognized as causative agents to numerous rare syndromes with concomitant GHD. Accordingly, this review provides researchers with a comprehensive up-to-date collection of the common and uncommon mouse models of GHD that have been used to study various aspects of physiology and metabolism associated with multiple forms of GHD. For each mouse line presented, the closest comparable human syndromes are discussed providing important parallels to the clinic.
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Affiliation(s)
- Edward O List
- Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA
- Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Athens, OH 45701, USA
| | - Reetobrata Basu
- Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA
| | - Darlene E Berryman
- Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Athens, OH 45701, USA
| | | | - Gabriel Á Martos-Moreno
- Department of Endocrinology & Pediatrics, Hospital Infantil Universitario Niño Jesús, IIS La Princesa & Universidad Autónoma de Madrid. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E28009, Spain
| | - John J Kopchick
- Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Athens, OH 45701, USA
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Suda M, Paul KH, Tripathi U, Minamino T, Tchkonia T, Kirkland JL. Targeting Cell Senescence and Senolytics: Novel Interventions for Age-Related Endocrine Dysfunction. Endocr Rev 2024; 45:655-675. [PMID: 38500373 PMCID: PMC11405506 DOI: 10.1210/endrev/bnae010] [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: 08/23/2023] [Revised: 01/11/2024] [Accepted: 03/12/2024] [Indexed: 03/20/2024]
Abstract
Multiple changes occur in hormonal regulation with aging and across various endocrine organs. These changes are associated with multiple age-related disorders and diseases. A better understanding of responsible underling biological mechanisms could help in the management of multiple endocrine disorders over and above hormone replacement therapy (HRT). Cellular senescence is involved in multiple biological aging processes and pathologies common in elderly individuals. Cellular senescence, which occurs in many older individuals but also across the lifespan in association with tissue damage, acute and chronic diseases, certain drugs, and genetic syndromes, may contribute to such endocrine disorders as osteoporosis, metabolic syndrome, and type 2 diabetes mellitus. Drugs that selectively induce senescent cell removal, "senolytics,", and drugs that attenuate the tissue-destructive secretory state of certain senescent cells, "senomorphics," appear to delay the onset of or alleviate multiple diseases, including but not limited to endocrine disorders such as diabetes, complications of obesity, age-related osteoporosis, and cancers as well as atherosclerosis, chronic kidney disease, neurodegenerative disorders, and many others. More than 30 clinical trials of senolytic and senomorphic agents have already been completed, are underway, or are planned for a variety of indications. Targeting senescent cells is a novel strategy that is distinct from conventional therapies such as HRT, and thus might address unmet medical needs and can potentially amplify effects of established endocrine drug regimens, perhaps allowing for dose decreases and reducing side effects.
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Affiliation(s)
- Masayoshi Suda
- Departments of Medicine and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
| | - Karl H Paul
- Departments of Medicine and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
- Department of Physiology and Pharmacology, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden
| | - Utkarsh Tripathi
- Departments of Medicine and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
| | - Tohru Minamino
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
- Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Tokyo, 100-0004, Japan
| | - Tamara Tchkonia
- Departments of Medicine and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
| | - James L Kirkland
- Departments of Medicine and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA
- Division of General Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
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Yang L, Li C, Song T, Zhan X. Growth hormone proteoformics atlas created to promote predictive, preventive, and personalized approach in overall management of pituitary neuroendocrine tumors. EPMA J 2023; 14:443-456. [PMID: 37605654 PMCID: PMC10439873 DOI: 10.1007/s13167-023-00329-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 06/14/2023] [Indexed: 08/23/2023]
Abstract
Human growth hormone (GH) is the indispensable hormone for the maintenance of normal physiological functions of the human body, including the growth, development, metabolism, and even immunoregulation. The GH is synthesized, secreted, and stored by somatotroph cells in adenohypophysis. Abnormal GH is associated with various GH-related diseases, such as acromegaly, dwarfism, diabetes, and cancer. Currently, some studies found there are dozens or even hundreds of GH proteoforms in tissue and serum as well as a series of GH-binding protein (GHBP) proteoforms and GH receptor (GHR) proteoforms were also identified. The structure-function relationship of protein hormone proteoforms is significantly important to reveal their overall physiological and pathophysiological mechanisms. We propose the use of proteoformics to study the relationship between every GH proteoform and different physiological/pathophysiological states to clarify the pathogenic mechanism of GH-related disease such as pituitary neuroendocrine tumor and conduct precise molecular classification to promote predictive preventive personalized medicine (PPPM / 3P medicine). This article reviews GH proteoformics in GH-related disease such as pituitary neuroendocrine tumor, which has the potential role to provide novel insight into pathogenic mechanism, discover novel therapeutic targets, identify effective GH proteoform biomarker for patient stratification, predictive diagnosis, and prognostic assessment, improve therapy method, and further accelerate the development of 3P medicine.
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Affiliation(s)
- Lamei Yang
- Medical Science and Technology Innovation Center, and Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong 250117 People’s Republic of China
| | - Chunling Li
- Department of Anesthesiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008 People’s Republic of China
| | - Tao Song
- Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021 People’s Republic of China
| | - Xianquan Zhan
- Medical Science and Technology Innovation Center, and Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong 250117 People’s Republic of China
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Okamura E, Ikeda K, Mano-Usui F, Kawashima S, Kondo A, Inagaki N. Augmentation of Growth Hormone by Chewing in Females. Nutrients 2023; 15:3628. [PMID: 37630818 PMCID: PMC10458618 DOI: 10.3390/nu15163628] [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: 07/06/2023] [Revised: 08/11/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
Sarcopenia is an age-related condition characterized by progressive loss of muscle mass and strength. Age-related decline in the secretion of growth hormone (GH), a condition called somatopause, is thought to play a role in sarcopenia. As pharmacological GH has adverse effects, we attempted to increase physiological GH. While the relationship between chewing and ghrelin levels has been studied, there are no reports on the relationship between chewing and GH. The aim of this study was to clarify the effects of chewing on the muscle anabolic hormones serum GH and plasma ghrelin. Thirteen healthy adults ingested a chewy nutrition bar containing 5.56 g of protein, 12.71 g of carbohydrate, and 0.09 g of fat on two different days, chewing before swallowing in one trial and swallowing without chewing in the other. Blood samples were taken before and after ingestion (0, 15, 30, and 60 min); GH, acylated ghrelin, glucose, insulin, amino acids, and lactate were measured. Two-way repeated ANOVA revealed a significant difference in the GH concentrations between the "Chew trial" and "Swallow trial" in females (p = 0.0054). However, post-hoc analyses found no statistically significant difference at each time point. The area under the curve of the percentage increase in GH was significantly increased in the "Chew trial" compared with the "Swallow trial" in females (12,203 ± 15,402% min vs. 3735 ± 988% min, p = 0.0488). Chewing had no effect on glucose, insulin, amino acids, or lactate concentrations. Thus, we found that chewing a protein supplement rather than swallowing it without chewing elevates the blood GH concentration. These results serve as a rationale for larger research and longitudinal studies to confirm the impacts of chewing on GH secretion.
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Affiliation(s)
- Emi Okamura
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (E.O.)
| | - Kaori Ikeda
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (E.O.)
- Department of Clinical Research Facilitation, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto 606-8507, Japan
| | - Fumika Mano-Usui
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (E.O.)
| | - Sachiko Kawashima
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (E.O.)
- Preemptive Medicine and Lifestyle Related Disease Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan
| | - Aki Kondo
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (E.O.)
| | - Nobuya Inagaki
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; (E.O.)
- Medical Research Institute KITANO HOSPITAL, P.I.I.F. Tazuke-Kofukai, Osaka 530-8480, Japan
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Alehagen U, Johansson P, Svensson E, Aaseth J, Alexander J. Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in Sweden. Eur J Nutr 2022; 61:3135-3148. [PMID: 35381849 PMCID: PMC9363287 DOI: 10.1007/s00394-022-02876-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 03/17/2022] [Indexed: 12/12/2022]
Abstract
Purpose Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers. Methods Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780. Results In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (β = 0.74; p < 0.001) and myocardium (β = 0.65; p < 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality. Conclusion Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10.
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Affiliation(s)
- Urban Alehagen
- Division of Cardiovascular Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, 581 85, Linköping, Sweden.
| | - Peter Johansson
- Department of Health, Medicine and Caring Sciences, Linköping University, 601 74, Norrköping, Sweden
| | | | - Jan Aaseth
- Research Department, Innlandet Hospital Trust, 2381, Brumunddal, Norway.,Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, 2418, Elverum, Norway
| | - Jan Alexander
- Norwegian Institute of Public Health, 0403, Oslo, Norway
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Dawes JJ, Scott J, Canetti EFD, Lockie RG, Schram B, Orr RM. Profiling the New Zealand Police Trainee Physical Competency Test. Front Public Health 2022; 10:821451. [PMID: 35242733 PMCID: PMC8885596 DOI: 10.3389/fpubh.2022.821451] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 01/18/2022] [Indexed: 12/25/2022] Open
Abstract
Police officers require a certain amount of occupational fitness to successfully perform physically demanding tasks. As such, trainees are required to undergo training to develop their ability to perform such tasks. The physical competency test (PCT) is a 400 m obstacle course consisting of key police occupational physical tasks used to evaluate a trainee's ability to complete tasks that a police officer is expected to perform whilst on duty. The purpose of this study was to profile the PCT in a police recruit population to provide an indication of the current level of occupational fitness within a policing population to inform conditioning requirements. Retrospective data for 813 male (age = 27.41 ± 5.92 years, body mass = 83.98 ± 14.03 kg, height = 179.23 ± 10.50 cm, BMI = 25.85 ± 3.92 kg/m2) and 372 female (mean age = 27.01 ± 6.45 years, mean weight = 67.14 ± 8.60 kg, mean height = 168.14 ± 6.46 cm and mean BMI = 23.61 ± 2.52 kg/m2) police trainees from the New Zealand Police Constabulary Recruitment database were provided for analysis. Anthropometric data, including height, body mass, and BMI were provided, in addition to trainee PCT time. Data were split by sex and age. Significant differences were observed between sexes for all anthropometric measures and PCT time (p < 0.001). Generally, in both the male and female groups, younger recruits tended to perform better than the older recruits with results between the "under 20" and the 20-24-year-old-age groups performing significantly better than the 35-39-year-old-age group in both sexes, and the 25-29-year-old-age group performing significantly better than the 35-39-year-old-age group in female officers. The data provided in this study provides a profile for performance of male and female recruits of various ages on the PCT in preparation for entry, or re-entry following injury, into the NZ Police. However, given that the PCT is considered a measure of occupational task performance, consideration should be given to the use of sex and age neutral requirements as the occupational tasks performed by police officers exhibit the same traits regardless of sex or age. Older trainees may therefore need conditioning to improve PCT times and subsequently occupational performance.
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Affiliation(s)
- J. Jay Dawes
- School of Kinesiology, Applied Health, and Recreation, Oklahoma State University, Stillwater, OK, United States
| | - Jordan Scott
- Faculty of Health Sciences and Medicine, Bond Institute of Health and Sport, Bond University, Robina, QLD, Australia
| | - Elisa F. D. Canetti
- Faculty of Health Sciences and Medicine, Bond Institute of Health and Sport, Bond University, Robina, QLD, Australia
- Tactical Research Unit, Bond University, Robina, QLD, Australia
| | - Robert G. Lockie
- Department of Kinesiology, California State University, Fullerton, Fullerton, CA, United States
| | - Ben Schram
- Faculty of Health Sciences and Medicine, Bond Institute of Health and Sport, Bond University, Robina, QLD, Australia
- Tactical Research Unit, Bond University, Robina, QLD, Australia
| | - Robin M. Orr
- Faculty of Health Sciences and Medicine, Bond Institute of Health and Sport, Bond University, Robina, QLD, Australia
- Tactical Research Unit, Bond University, Robina, QLD, Australia
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Hormonal and metabolic responses of older adults to resistance training in normobaric hypoxia. Eur J Appl Physiol 2022; 122:1007-1017. [PMID: 35142944 DOI: 10.1007/s00421-022-04897-4] [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: 03/30/2021] [Accepted: 01/06/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE In young adults, the hormonal responses to resistance exercise are amplified by normobaric hypoxia. Hormone concentrations and metabolism are typically dysregulated with age, yet the impact of hypoxia on these responses to resistance exercise are uncharacterised. Therefore, this study aimed to characterise the acute and chronic hormonal and metabolic responses of older adults to resistance training in normobaric hypoxia. METHODS Adults aged 60-75 years completed 8 weeks of resistance training in either normoxia (20.9% O2; n = 10) or normobaric hypoxia (14.4% O2, n = 10) twice weekly at 70% of their predicted 1-repetition maximum. Growth hormone, glucose, lactate, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), cortisol, total testosterone, adrenaline, noradrenaline and dopamine were quantified at pre- and post-training, and in the 60 min following the first training session (untrained state) and the last training session (trained state). RESULTS Eight weeks of training in hypoxia did not affect the resting levels of the hormones or physiological factors measured. However, hypoxia significantly blunted the acute growth hormone response in the 15 min following the last training session at week eight (43.87% lower in the hypoxic group; p = 0.017). This novel and unexpected finding requires further investigation. All other hormones were unaffected acutely by hypoxia in the 60 min following the first and the last training session. CONCLUSION Chronic resistance training in normobaric hypoxia supresses the growth hormone response to exercise in older adults. All other hormones and metabolic markers were unaffected both acutely and chronically by hypoxia.
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Blackmore DG, Steyn FJ, Carlisle A, O'Keeffe I, Vien KY, Zhou X, Leiter O, Jhaveri D, Vukovic J, Waters MJ, Bartlett PF. An exercise "sweet spot" reverses cognitive deficits of aging by growth-hormone-induced neurogenesis. iScience 2021; 24:103275. [PMID: 34761193 PMCID: PMC8567379 DOI: 10.1016/j.isci.2021.103275] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/09/2021] [Accepted: 10/12/2021] [Indexed: 11/02/2022] Open
Abstract
Hippocampal function is critical for spatial and contextual learning, and its decline with age contributes to cognitive impairment. Exercise can improve hippocampal function, however, the amount of exercise and mechanisms mediating improvement remain largely unknown. Here, we show exercise reverses learning deficits in aged (24 months) female mice but only when it occurs for a specific duration, with longer or shorter periods proving ineffective. A spike in the levels of growth hormone (GH) and a corresponding increase in neurogenesis during this sweet spot mediate this effect because blocking GH receptor with a competitive antagonist or depleting newborn neurons abrogates the exercise-induced cognitive improvement. Moreover, raising GH levels with GH-releasing hormone agonist improved cognition in nonrunners. We show that GH stimulates neural precursors directly, indicating the link between raised GH and neurogenesis is the basis for the substantially improved learning in aged animals.
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Affiliation(s)
- Daniel G Blackmore
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Frederik J Steyn
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, Australia
| | - Alison Carlisle
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Imogen O'Keeffe
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
| | - King-Year Vien
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Xiaoqing Zhou
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Odette Leiter
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Dhanisha Jhaveri
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.,Mater Research Institute, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Jana Vukovic
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.,School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Michael J Waters
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Perry F Bartlett
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
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Sudhir G, Jayabalan V, Sellayee S, Gadde S, Kailash K. Is there an interdependence between paraspinal muscle mass and lumbar disc degeneration? A MRI based study at 2520 levels in 504 patients. J Clin Orthop Trauma 2021; 22:101576. [PMID: 34532219 PMCID: PMC8429962 DOI: 10.1016/j.jcot.2021.101576] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 07/27/2021] [Accepted: 08/30/2021] [Indexed: 10/20/2022] Open
Abstract
INTRODUCTION Low back pain is one of the most common cause for outpatient visits. Though few studies have shown the vital role of paraspinal muscles in lumbar spine pathology, literature is scarce regarding the influence of the paraspinal muscles in disc degeneration. We aimed to analyse the correlation between paraspinal muscles and disc degeneration. METHODS This is a Level III Prospective Cohort Study done in MRI of lumbosacral spine in 504 patients at 2520 levels from L1-2 to L5-S1. The parameters assessed were age, Pfirrmann grade for disc degeneration and paraspinal muscle (Multifidus and Erector Spinae) mass assessed by the gross cross sectional area of the muscle.The values and their correlation was analyzed using SPSS software. RESULTS The study included a total of 504 patients (231 males and 273 females) with a mean age of 52.00 ± 15.00 (22-80) years. The mean GCSA in cm2 of the paraspinal muscles at L1-L2, L2-L3,L3-L4,L4-L5,L5-S1 were 16.177 ± 2.72, 17.275 ± 2.16, 16.900 ± 3.07, 16.800 ± 2.63, 13.426 ± 2.42 respectively. We found that the age of the patient is directly proportional to the disc degeneration and inversely proportional to GCSA of paraspinal muscle. There was a significant negative correlation between disc degeneration and paraspinal muscle mass. CONCLUSION We found that the paraspinal muscle mass reduces and Pfirrman's Grade increases as age advances. Also patients with disc degeneration tend to have wasting of paraspinal muscles and vice versa. Hence, strengthening the paraspinal muscles should be emphasised to prevent back pain and to stall the degeneration cascade.
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Affiliation(s)
| | - Vignesh Jayabalan
- Corresponding author. Department of Spine Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
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Age-related expression of prominent regulatory elements in mouse brain: catastrophic decline of FOXO3a. GeroScience 2021; 43:1935-1946. [PMID: 33864227 DOI: 10.1007/s11357-021-00364-8] [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: 11/01/2020] [Accepted: 04/06/2021] [Indexed: 10/21/2022] Open
Abstract
Aging is associated with changes in regulation, particularly among diverse regulators in the brain. We assayed prominent regulatory elements in mouse brain to explore their relationship to one another, stress, and aging. Notably, unphosphorylated (activated) forkhead transcription factor 3a (uFOXO3a) expressed exponential decline congruent with increasing age-related mortality. Decline in uFOXO3a would impact homeostasis, aging rate, stress resistance, and mortality. We also examined other regulators associated with aging and FOXO3a: protein kinase B (PKB), the mechanistic target of rapamycin (mTOR), 70 kDa ribosomal S6 kinase (P70S6K), and 5' AMP-activated protein kinase (AMPK). It would require powerful regulatory distortion, conflicting tradeoffs and/or significant damage to inflict exponential decline of a transcription factor as crucial as FOXO3a. No other regulator examined expressed an exponential pattern congruent with aging. PKB was strongly associated with decreases in uFOXO3a, but the aging pattern of PKB did not support a causal linkage. Although mTOR expressed a trend for age-related increase, this was not significant. We considered that the mTOR downstream element, P70S6K, might suppress FOXO3a, but remarkably, it expressed a strong positive association. The age-related pattern of AMPK was also incompatible. Literature suggested the immunological regulator NFĸB (nuclear factor kappa-light-chain-enhancer of activated B cells) increases with age and suppresses FOXO3a. This would inhibit apoptosis, autophagy, mitophagy, proteostasis, detoxification, antioxidants, chaperones, and DNA repair, thus exacerbating aging. We conclude that a key aspect of aging involves distortion of key regulators in the brain.
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Insulin-Like Growth Factor 1 Related to Chronic Low-Grade Inflammation in Patients with Obesity and Early Change of its Levels After Laparoscopic Sleeve Gastrectomy. Obes Surg 2021; 30:3326-3332. [PMID: 32410151 DOI: 10.1007/s11695-020-04473-9] [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] [Indexed: 10/24/2022]
Abstract
BACKGROUND Insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein (IGFBP) have an influence on metabolism. However, changes in metabolism after sleeve gastrectomy (SG) are not clearly known. This study investigated the change in IGFBP3 levels in obesity after bariatric surgery. METHODS We evaluated 36 patients with obesity (14 males, aged 31.36 ± 7.06 years and 22 females, aged 32.55 ± 11.40 years) at baseline and 3 months after SG. Changes in their IGF1, IGFBP3, and IGF1/IGFBP3 ratios and glucose-lipid metabolic, inflammation, and oxidative stress parameters were measured. Enzyme-linked immunosorbent assay was used to measure their IGF1 and IGFBP3 levels. RESULTS (1) IGFBP3 levels were negatively associated with waist circumference (WC) and waist-to-hip ratio (r = - 0.482, P = 0.043; r = - 0.503, P = 0.033); total IGF1 levels were negatively associated with body mass index and WC (r = - 0.569, P = 0.014; r = - 0.470, P = 0.048); and free IGF1 levels were negatively related to tumor necrosis factor (TNF)-α level independent of age (r = - 0.544, P = 0.020). Free IGF1 levels were negatively associated with uric acid, interleukin-6 (IL-6), IL-8, and TNF-α levels (r = - 0.646, P = 0.032; r = - 0.667, P = 0.025; r = - 0.641, P = 0.033; r = - 0.733, P = 0.010) and positively associated with superoxide dismutase activity (r = 0.635, P = 0.036) in females; this relation was not significant in males (all P > 0.05). Total IGF1 was also negatively associated with C-reactive protein (CRP) level in females (r = - 0.671, P = 0.024). (2) IGFBP3 level significantly decreased at 3 months after bariatric surgery in females (P < 0.001) but not in males (P = 0.815). Total IGF1 level significantly decreased after bariatric surgery (P = 0.048); the change was also significant in females (P = 0.014) but not in males (P = 0.626). Free IGF1 level after bariatric surgery was not statistically different between males (P = 0.605) and females (P = 0.628). (3) In females, the change in IGFBP3 level was associated with a change in high-density lipoprotein cholesterol and free fatty acid levels (r = 0.607, P = 0.003; r = 0.546, P = 0.016), and a change in total IGF1 level was associated with a change in CRP level (r = 0.664, P = 0.009). CONCLUSION IGF1 level was related to chronic low-grade inflammation and oxidative stress in obesity, especially in females. IGFBP3 and IGF1 levels decreased in obesity after SG, especially in females. Changes in IGF/IGFBP3 levels were associated with a change in the inflammatory state after surgery.
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Scarano E, Riccio E, Somma T, Arianna R, Romano F, Di Benedetto E, de Alteriis G, Colao A, Di Somma C. Impact of Long-Term Growth Hormone Replacement Therapy on Metabolic and Cardiovascular Parameters in Adult Growth Hormone Deficiency: Comparison Between Adult and Elderly Patients. Front Endocrinol (Lausanne) 2021; 12:635983. [PMID: 33716985 PMCID: PMC7947790 DOI: 10.3389/fendo.2021.635983] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 01/14/2021] [Indexed: 11/13/2022] Open
Abstract
Growth hormone deficiency (GHD) in adults is due to a reduced growth hormone (GH) secretion by the anterior pituitary gland which leads to a well-known syndrome characterized by decreased cognitive function and quality of life (QoL), decreased bone mineral density (BMD), increased central adiposity with a reduction in lean body mass, decreased exercise tolerance, hyperlipidemia and increased predisposition to atherogenesis. Considering some similar features between aging and GHD, it was thought that the relative GH insufficiency of the elderly person could make an important contribution to the fragility of elderly. GH stimulation tests are able to differentiate GHD in elderly patients (EGHD) from the physiological reduction of GH secretion that occurs with aging. Although there is no evidence that rhGH replacement therapy increases the risk of developing Diabetes Mellitus (DM), reducing insulin sensitivity and inducing cardiac hypertrophy, long-term monitoring is, however, also mandatory in terms of glucose metabolism and cardiovascular measurements. In our experience comparing the impact of seven years of rhGH treatment on metabolic and cardiovascular parameters in GHD patients divided in two groups [adult (AGHD) and elderly (EGHD) GHD patients], effects on body composition are evident especially in AGHD, but not in EGHD patients. The improvements in lipid profile were sustained in all groups of patients, and they had a lower prevalence of dyslipidemia than the general population. The effects on glucose metabolism were conflicting, but approximately unchanged. The risk of DM type 2 is, however, probably increased in obese GHD adults with impaired glucose homeostasis at baseline, but the prevalence of DM in GHD is like that of the general population. The increases in glucose levels, BMI, and SBP in GHD negatively affected the prevalence of Metabolic Syndrome (MS) in the long term, especially in AGHD patients. Our results are in accordance to other long-term studies in which the effects on body composition and lipid profile are prominent.
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Affiliation(s)
- Elisabetta Scarano
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Enrico Riccio
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Teresa Somma
- Dipartimento di Neuroscienze e Scienze Riproduttive e Odontostomatologiche, Divisione di Neurochirurgia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Rossana Arianna
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Fiammetta Romano
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Elea Di Benedetto
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Giulia de Alteriis
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Annamaria Colao
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Carolina Di Somma
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli Federico II, Naples, Italy
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Priego T, Martín AI, González-Hedström D, Granado M, López-Calderón A. Role of hormones in sarcopenia. VITAMINS AND HORMONES 2021; 115:535-570. [PMID: 33706961 DOI: 10.1016/bs.vh.2020.12.021] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Aging involves numerous changes in body composition that include a decrease in skeletal muscle mass. The gradual reduction in muscle mass is associated with a simultaneous decrease in muscle strength, which leads to reduced mobility, fragility and loss of independence. This process called sarcopenia is secondary to several factors such as sedentary lifestyle, inadequate nutrition, chronic inflammatory state and neurological alterations. However, the endocrine changes associated with aging seem to be of special importance in the development of sarcopenia. On one hand, advancing age is associated with a decreased secretion of the main hormones that stimulate skeletal muscle mass and function (growth hormone, insulin-like growth factor 1 (IGFI), testosterone and estradiol). On the other hand, the alteration of the IGF-I signaling along with decreased insulin sensitivity also have an important impact on myogenesis. Other hormones that decline with aging such as the adrenal-derived dehydroepiandrosterone, thyroid hormones and vitamin D seem to also be involved in sarcopenia. Adipokines released by adipose tissue show important changes during aging and can affect muscle physiology and metabolism. In addition, catabolic hormones such as cortisol and angiotensin II can accelerate aged-induced muscle atrophy, as they are involved in muscle wasting and their levels increase with age. The role played by all of these hormones and the possible use of some of them as therapeutic tools for treating sarcopenia will be discussed.
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Affiliation(s)
- T Priego
- Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - A I Martín
- Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - D González-Hedström
- Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; Pharmactive Biotech Products S.L. Parque Científico de Madrid. Avenida del Doctor Severo Ochoa, 37 Local 4J, 28108 Alcobendas, Madrid, Spain
| | - M Granado
- Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; CIBER Fisiopatología de la Obesidad y Nutrición. Instituto de Salud Carlos III, Madrid, Spain
| | - A López-Calderón
- Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
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Abstract
Sarcopenia describes low muscle mass and strength associated with ageing, whilst reduced physical performance indicates the severity of the condition. It can happen independently of other medical conditions and can be a key feature of the frailty phenotype. Frailty is a syndrome of increased vulnerability to incomplete resolution of homeostasis, following a stressor event. Researchers have described the implications of hypothalamic pituitary dysregulation in the pathogenesis of both entities. This review summarizes the recent evidence in this area as well as other endocrine factors such as insulin resistance and vitamin D status and outlines current research priorities. We conducted searches to PubMed and Embase databases for articles, reviews and studies reporting new data on the interaction between hormones of the endocrine system and frailty and/ or sarcopenia in the last 5 years. Interventional studies, cohort studies, case-control studies and animal studies were included. Clinical trials register was also searched to identify ongoing relevant studies. Studies have given us insights into the complex relationships between factors such as anabolic hormones, glucocorticoids and vitamin D on muscle strength and performance and their involvement in ageing phenotypes. However, robust randomized controlled trials are needed to consolidate existing evidence in humans and inform clinical practice. Current evidence supports hormone replacement in patients with confirmed deficiencies, to optimize health and prevent complications. Hormone replacement has limited use for age-related conditions. Current interest is focused on muscle/bone/fat interactions and health outcomes in "sarcopenic obesity." A life-course approach to improving 'health-span' is advocated. Lifestyle factors such as nutrition and physical activity have important interactions with body composition, physical function and metabolic outcomes. Large-scale clinical trials will determine the efficacy and long-term safety of hormone supplementation in the management of sarcopenia and frailty.
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Affiliation(s)
- Vicky Kamwa
- Musculoskeletal Endocrinology Research Group, Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK - .,Academic Metabolic Bone Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK - .,Institute of Inflammation and Ageing, The University of Birmingham, Birmingham, UK -
| | - Carly Welch
- Institute of Inflammation and Ageing, The University of Birmingham, Birmingham, UK
| | - Zaki K Hassan-Smith
- Musculoskeletal Endocrinology Research Group, Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.,Academic Metabolic Bone Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Ohshima H, Adachi H, Enomoto M, Fukami A, Nakamura S, Nohara Y, Sakaue A, Morikawa N, Hamamura H, Toyomasu K, Yamamoto M, Fukumoto Y. Association between growth hormone and hypertension in a general population. Hypertens Res 2020; 43:1430-1436. [DOI: 10.1038/s41440-020-0500-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 05/27/2020] [Accepted: 06/01/2020] [Indexed: 12/28/2022]
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Pouriamehr S, Barmaki H, Rastegary M, Lotfi F, Nabi Afjadi M. Investigation of insulin-like growth factors/insulin-like growth factor binding proteins regulation in metabolic syndrome patients. BMC Res Notes 2019; 12:653. [PMID: 31601230 PMCID: PMC6788073 DOI: 10.1186/s13104-019-4492-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 07/17/2019] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVE The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are thought to play a significant role in metabolic pathways and glucose metabolism. Unregulated levels of IGFs/IGFBPs have been associated with the development of glucose intolerance and metabolic syndrome X (MSx). We hypothesized that change of IGFs/IGFBPs levels could increase the risk of MSx; thus, this study aimed to evaluate the serostatus of IGFs/IGFBPs in individuals with MSx. RESULTS After adjustment for metabolic parameters, MSx patients had a lower level of IGF-1, IGFBP-1, and IGFBP-2 compared with subjects in the control group. Further analysis revealed a positive correlation between serum levels of IGF-1 and IGF-2 (p < 0.05), as well as serum IGFBP-3 and IGF-2 (p < 0.05). Also, the statistical analysis showed a negative association of serum IGF-1 with plasma glucose and total cholesterol levels (p < 0.05). Besides, a negative relationship was found between serum concentrations of IGF-1/IGF-2 and the risk of developing MSx. These data indicated that some components of IGFs/IGFBPs are linked with the pathogenesis of MSx. In conclusion, these inverse associations showed a possible linkage between the IGF/IGFBP signaling pathway and the development of MSx. It seems the decreased concentrations of IGFs edmay be regarded as a potential biomarker for early diagnosis or even prognosis of MSx but need more systematic studies to confirmed it.
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Affiliation(s)
- Somayeh Pouriamehr
- Department of Biology, Dezful Branch, Islamic Azad University, Dezful, Iran
| | - Haleh Barmaki
- Department of Laboratory Medicine, Faculty of Para Medical Sciences, Shahid Behest University of Medical Sciences, Tehran, Iran
| | - Mozhdeh Rastegary
- Department of Biology, Basic Science Faculty, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Farzaneh Lotfi
- Department of Clinical Biochemistry, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Dai GC, Li YJ, Chen MH, Lu PP, Rui YF. Tendon stem/progenitor cell ageing: Modulation and rejuvenation. World J Stem Cells 2019; 11:677-692. [PMID: 31616543 PMCID: PMC6789185 DOI: 10.4252/wjsc.v11.i9.677] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 08/15/2019] [Accepted: 09/04/2019] [Indexed: 02/06/2023] Open
Abstract
Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury. The role of tendon stem/progenitor cells (TSPCs) in tendon maintenance and regeneration has received increasing attention in recent years. The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect, or cause ageing, and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment. In this review, recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs, including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process, are analyzed. During the ageing process, TSPCs ageing might occur as a natural part of the tendon ageing, but could also result from decreased levels of growth factor, hormone deficits and changes in other related factors. Here, we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing, including moderate exercise, cell extracellular matrix condition, growth factors and hormones; these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.
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Affiliation(s)
- Guang-Chun Dai
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ying-Juan Li
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China
| | - Min-Hao Chen
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Pan-Pan Lu
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China.
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Li Y, Dai G, Shi L, Lin Y, Chen M, Li G, Rui Y. The Potential Roles of Tendon Stem/Progenitor Cells in Tendon Aging. Curr Stem Cell Res Ther 2019; 14:34-42. [PMID: 30332976 DOI: 10.2174/1574888x13666181017112233] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 09/15/2018] [Accepted: 10/02/2018] [Indexed: 12/15/2022]
Abstract
Aging is a key dangerous factor for the occurrence and severity of tendon injury, but the exact cognition of the relationship is elusive at present. More previous studies suggest age-related changes occur at tendon mechanical properties, structure and composition, but the pathological alternations may be overlooked, which might be a cause for the structure and function variations, and even speed up the progress of age-related disorders. Recently, the presence of tendon stem/progenitor cells (TSPCs) would provide new insights for the pathogenesis of tendon aging. In this review, the tendon mechanical properties, structure and composition are presented in brief, then, the pathological changes of the aging tendon are described firstly, and the latest researches on alterations of TSPCs in the pathogenesis of tendon aging have also been analyzed. At a cellular level, the hypothetical model of altered TSPCs fate for tendon aging is also proposed. Moreover, the regulation of TSPCs as a potential way of the therapies for age-related tendon diseases is discussed. Therefore, reversing the impaired function of TSPCs and promoting the tenogenic differentiation of TSPCs could become hot spots for further study and give the opportunity to establish new treatment strategies for age-related tendon injuries.
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Affiliation(s)
- Yingjuan Li
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, China
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China
- China Orthopedic Regenerative Medicine Group, Hangzhou, Zhejiang 310000, China
| | - Guangchun Dai
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Liu Shi
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
- Program of Stem Cell and Regeneration, School of Biomedical Science, and Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Yucheng Lin
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Minhao Chen
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Gang Li
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
- Program of Stem Cell and Regeneration, School of Biomedical Science, and Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Yunfeng Rui
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China
- China Orthopedic Regenerative Medicine Group, Hangzhou, Zhejiang 310000, China
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
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Pamphlett R, Kum Jew S, Doble PA, Bishop DP. Elemental Analysis of Aging Human Pituitary Glands Implicates Mercury as a Contributor to the Somatopause. Front Endocrinol (Lausanne) 2019; 10:419. [PMID: 31297094 PMCID: PMC6607410 DOI: 10.3389/fendo.2019.00419] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Accepted: 06/12/2019] [Indexed: 12/22/2022] Open
Abstract
Background: Growth hormone levels often decline on aging, and this "somatopause" is associated with muscle and bone loss, visceral adiposity and impaired cardiovascular function. Mercury has been detected in human pituitary glands, so to see if mercury could play a part in the somatopause we measured the proportion of people at different ages who had mercury in their anterior pituitary cells. Materials and methods: Paraffin sections of pituitary glands taken at autopsy from 94 people between the ages of 2 and 99 years were stained for inorganic mercury using autometallography. Pituitary mercury content was classified as none, low (<30% of cells) or high (>30% of cells) in increasing two-decade age groups. Autometallography combined with immunohistochemistry determined which hormone-producing cells contained mercury. Laser ablation-inductively coupled plasma-mass spectrometry was used to confirm the presence of mercury. Results: The proportion of people with low-content pituitary mercury remained between 33 and 42% at all ages. The proportion of people with high-content mercury increased with increasing age, from 0% of people in the 2-20 year group to a peak of 50% of people in the 61-80 years group, followed by a fall to 35% of people in the 81-99 years group. Mercury, when present, was found always in somatotrophs, occasionally in corticotrophs, rarely in thyrotrophs and gonadotrophs, and never in lactotrophs. Laser ablation-inductively coupled plasma-mass spectrometry detected mercury in regions of pituitaries that stained with autometallography. Conclusions: The proportion of people with mercury in their anterior pituitary cells, mostly somatotrophs, increases with aging, suggesting that mercury toxicity could be one factor contributing to the decline in growth hormone levels found in advancing age.
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Affiliation(s)
- Roger Pamphlett
- Discipline of Pathology, Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- *Correspondence: Roger Pamphlett
| | - Stephen Kum Jew
- Discipline of Pathology, Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Philip A. Doble
- The Atomic Medicine Initiative, University of Technology, Sydney, NSW, Australia
| | - David P. Bishop
- The Atomic Medicine Initiative, University of Technology, Sydney, NSW, Australia
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21
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Reddi S, Mada SB, Kumar N, Kumar R, Ahmad N, Karvande A, Kapila S, Kapila R, Trivedi R. Antiosteopenic Effect of Buffalo Milk Casein-Derived Peptide (NAVPITPTL) in Ovariectomized Rats. Int J Pept Res Ther 2018. [DOI: 10.1007/s10989-018-9763-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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22
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Scicchitano BM, Dobrowolny G, Sica G, Musarò A. Molecular Insights into Muscle Homeostasis, Atrophy and Wasting. Curr Genomics 2018; 19:356-369. [PMID: 30065611 PMCID: PMC6030854 DOI: 10.2174/1389202919666180101153911] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Muscle homeostasis is guaranteed by a delicate balance between synthesis and degradation of cell proteins and its alteration leads to muscle wasting and diseases. In this review, we describe the major anabolic pathways that are involved in muscle growth and homeostasis and the proteolytic systems that are over-activated in muscle pathologies. Modulation of these pathways comprises an attractive target for drug intervention.
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Affiliation(s)
- Bianca Maria Scicchitano
- Istituto di Istologia e Embriologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Largo Francesco Vito 1-00168, Roma, Italy
| | - Gabriella Dobrowolny
- Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy
| | - Gigliola Sica
- Istituto di Istologia e Embriologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Largo Francesco Vito 1-00168, Roma, Italy
| | - Antonio Musarò
- Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome, Italy
- DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy
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23
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Paragliola RM, Salvatori R. Novel Somatostatin Receptor Ligands Therapies for Acromegaly. Front Endocrinol (Lausanne) 2018; 9:78. [PMID: 29563895 PMCID: PMC5845985 DOI: 10.3389/fendo.2018.00078] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 02/20/2018] [Indexed: 12/21/2022] Open
Abstract
Surgery is considered the treatment of choice in acromegaly, but patients with persistent disease after surgery or in whom surgery cannot be considered require medical therapy. Somatostatin receptor ligands (SRLs) octreotide (OCT), lanreotide, and the more recently approved pasireotide, characterized by a broader receptor ligand binding profile, are considered the mainstay in the medical management of acromegaly. However, in the attempt to offer a more efficacious and better tolerated medical approach, recent research has been aimed to override some limitations related to the use of currently approved drugs and novel SRLs therapies, with potential attractive features, have been proposed. These include both new formulation of older molecules and new molecules. Novel OCT formulations are aimed in particular to improve patients' compliance and to reduce injection discomfort. They include an investigational ready-to-use subcutaneous depot OCT formulation (CAM2029), delivered via prefilled syringes and oral OCT that uses a "transient permeability enhancer" technology, which allows for OCT oral absorption. Another new delivery system is a long-lasting OCT implant (VP-003), which provide stable doses of OCT throughout a period of several months. Finally, a new SRL DG3173 (somatoprim) seems to be more selective for GH secretion, suggesting possible advantages in the presence of hyperglycemia or diabetes. How much these innovations will actually be beneficial to acromegaly patients in real clinical practice remains to be seen.
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Affiliation(s)
| | - Roberto Salvatori
- Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, Pituitary Center Johns Hopkins University School of Medicine, Baltimore, MD, United States
- *Correspondence: Roberto Salvatori,
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24
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MRI-defined paraspinal muscle morphology in Japanese population: The Wakayama Spine Study. PLoS One 2017; 12:e0187765. [PMID: 29117256 PMCID: PMC5678698 DOI: 10.1371/journal.pone.0187765] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 10/25/2017] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE This study aimed to establish sex- and age-dependent distributions of the cross sectional area and fatty infiltration ratio of paraspinal muscles, and to examine the correlation between paraspinal muscle degeneration and low back pain in the Japanese population. METHODS In this cross-sectional study, data from 796 participants (241 men, 555 women; mean age, 63.5 years) were analyzed. The measurement of the cross sectional area and fatty infiltration ratio of the erector spinae and multifidus from the level of T12/L1 to L4/5 and psoas major at the level of T12/L1 was performed using axial T2-weighted magnetic resonance imaging. Multivariate logistic regression analysis was used to estimate the association between fatty infiltration of the paraspinal muscles and the prevalence of low back pain. RESULTS The cross sectional area was larger in men than women, and tended to decrease with age, with the exception of the erector spinae at T12/L1 and L1/2 in women. The fatty infiltration ratio was lower in men than women, except for multifidus at T12/L1 in 70-79 year-olds and psoas major in those less than 50 years-old, and tended to increase with age. Logistic regression analysis adjusted for age, sex, and body mass index showed that the fatty infiltration ratio of the erector spinae at L1/2 and L2/3 was significantly associated with low back pain (L1/2 level: odds ratio, 1.05; 95% confidence interval, 1.005-1.104; L2/3 level: odds ratio, 1.05; 95% confidence interval, 1.001-1.113). CONCLUSION This study measured the cross sectional area and fatty infiltration ratio of paraspinal muscles in the Japanese population using magnetic resonance imaging, and demonstrated that the fatty infiltration ratio of the erector spinae in the upper lumbar spine was significantly associated with the presence of low back pain. The measurements could be used as reference values, which are important for future comparative studies.
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25
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Perice L, Barzilai N, Verghese J, Weiss EF, Holtzer R, Cohen P, Milman S. Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function. Aging (Albany NY) 2017; 8:2414-2424. [PMID: 27744417 PMCID: PMC5115897 DOI: 10.18632/aging.101063] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 09/28/2016] [Indexed: 12/21/2022]
Abstract
Mutations that reduce somatotropic signaling result in improved lifespan and health-span in model organisms and humans. However, whether reduced circulating insulin-like growth factor-I (IGF-I) level is detrimental to cognitive and muscle function in older adults remains understudied. A cross-sectional analysis was performed in Ashkenazi Jews with exceptional longevity (age ≥95 years). Cognition was assessed using the Mini-Mental State Examination and muscle function with the chair rise test, grip-strength, and gait speed. Muscle mass was estimated using the skeletal muscle index. Serum IGF-I was measured with liquid chromatography mass spectrometry. In gender stratified age-adjusted logistic regression analysis, females with IGF-I levels in the first tertile had lower odds of being cognitively impaired compared to females with IGF-I levels within the upper two tertiles, OR (95% CI) 0.39 (0.19-0.82). The result remained significant after adjustment for multiple parameters. No significant association was identified in males between IGF-I and cognition. No relationship was found between IGF-I tertiles and muscle function and muscle mass in females or males. Lower circulating IGF-I is associated with better cognitive function in females with exceptional longevity, with no detriment to skeletal muscle mass and function.
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Affiliation(s)
- Leland Perice
- Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Nir Barzilai
- Department of Medicine, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.,Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Joe Verghese
- Department of Medicine, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.,Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Erica F Weiss
- Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Roee Holtzer
- Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.,Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY 10461
| | - Pinchas Cohen
- Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA
| | - Sofiya Milman
- Department of Medicine, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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26
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Alehagen U, Johansson P, Aaseth J, Alexander J, Brismar K. Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. PLoS One 2017; 12:e0178614. [PMID: 28609475 PMCID: PMC5469470 DOI: 10.1371/journal.pone.0178614] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Accepted: 05/14/2017] [Indexed: 12/11/2022] Open
Abstract
Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; P<0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.
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Affiliation(s)
- Urban Alehagen
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
- * E-mail:
| | - Peter Johansson
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
- Department of Social and Welfare Studies, Linköping University, Norrköping, Sweden
| | - Jan Aaseth
- Research Department, Innlandet Hospital Trust, Brumunddal, Norway, and Hedmark University of Applied Sciences, Elverum, Norway
| | - Jan Alexander
- Norwegian Institute of Public Health, Oslo, and Norwegian University of Life Sciences (NMBU), Ås, Norway
| | - Kerstin Brismar
- Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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27
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von Haehling S, Ebner N, Dos Santos MR, Springer J, Anker SD. Muscle wasting and cachexia in heart failure: mechanisms and therapies. Nat Rev Cardiol 2017; 14:323-341. [PMID: 28436486 DOI: 10.1038/nrcardio.2017.51] [Citation(s) in RCA: 260] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Body wasting is a serious complication that affects a large proportion of patients with heart failure. Muscle wasting, also known as sarcopenia, is the loss of muscle mass and strength, whereas cachexia describes loss of weight. After reaching guideline-recommended doses of heart failure therapies, the most promising approach to treating body wasting seems to be combined therapy that includes exercise, nutritional counselling, and drug treatment. Nutritional considerations include avoiding excessive salt and fluid intake, and replenishment of deficiencies in trace elements. Administration of omega-3 polyunsaturated fatty acids is beneficial in selected patients. High-calorific nutritional supplements can also be useful. The prescription of aerobic exercise training that provokes mild or moderate breathlessness has good scientific support. Drugs with potential benefit in the treatment of body wasting that have been tested in clinical studies in patients with heart failure include testosterone, ghrelin, recombinant human growth hormone, essential amino acids, and β2-adrenergic receptor agonists. In this Review, we summarize the pathophysiological mechanisms of muscle wasting and cachexia in heart failure, and highlight the potential treatment strategies. We aim to provide clinicians with the relevant information on body wasting to understand and treat these conditions in patients with heart failure.
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Affiliation(s)
- Stephan von Haehling
- Department of Cardiology and Pneumology, University of Göttingen Medical Centre and DZHK (German Centre for Cardiovascular Research), Robert-Koch-Strasse 40, D-37075 Göttingen, Germany
| | - Nicole Ebner
- Department of Cardiology and Pneumology, University of Göttingen Medical Centre and DZHK (German Centre for Cardiovascular Research), Robert-Koch-Strasse 40, D-37075 Göttingen, Germany
| | - Marcelo R Dos Santos
- Department of Cardiology and Pneumology, University of Göttingen Medical Centre and DZHK (German Centre for Cardiovascular Research), Robert-Koch-Strasse 40, D-37075 Göttingen, Germany.,Heart Institute (InCor), University of Sao Paulo Medical School, Dr. Arnaldo Avenue, 455 Cerqueira César, 01246903 Sao Paulo, Brazil
| | - Jochen Springer
- Department of Cardiology and Pneumology, University of Göttingen Medical Centre and DZHK (German Centre for Cardiovascular Research), Robert-Koch-Strasse 40, D-37075 Göttingen, Germany
| | - Stefan D Anker
- Department of Cardiology and Pneumology, University of Göttingen Medical Centre and DZHK (German Centre for Cardiovascular Research), Robert-Koch-Strasse 40, D-37075 Göttingen, Germany.,Division of Cardiology and Metabolism: Heart Failure, Cachexia and Sarcopenia, Department of Internal Medicine and Cardiology, Berlin-Brandenburg Centre for Regenerative Therapies, Charité Medical School, Augustenburger Platz 1, 13353 Berlin, Germany
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Guillermier C, Fazeli PK, Kim S, Lun M, Zuflacht JP, Milian J, Lee H, Francois-Saint-Cyr H, Horreard F, Larson D, Rosen ED, Lee RT, Lechene CP, Steinhauser ML. Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity. JCI Insight 2017; 2:e90349. [PMID: 28289709 DOI: 10.1172/jci.insight.90349] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Quantification of stable isotope tracers has revealed the dynamic state of living tissues. A new form of imaging mass spectrometry quantifies isotope ratios in domains much smaller than a cubic micron, enabling measurement of cell turnover and metabolism with stable isotope tracers at the single-cell level with a methodology we refer to as multi-isotope imaging mass spectrometry. In a first-in-human study, we utilize stable isotope tracers of DNA synthesis and de novo lipogenesis to prospectively measure cell birth and adipocyte lipid turnover. In a study of healthy adults, we elucidate an age-dependent decline in new adipocyte generation and adipocyte lipid turnover. A linear regression model suggests that the aging effect could be mediated by a decline in insulin-like growth factor-1 (IGF-1). This study therefore establishes a method for measurement of cell turnover and metabolism in humans with subcellular resolution while implicating the growth hormone/IGF-1 axis in adipose tissue aging.
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Affiliation(s)
- Christelle Guillermier
- Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.,Center for NanoImaging, Brigham and Women's Hospital, Cambridge, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Pouneh K Fazeli
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Soomin Kim
- Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Mingyue Lun
- Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jonah P Zuflacht
- Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jessica Milian
- Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Hang Lee
- Harvard Medical School, Boston, Massachusetts, USA.,Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | | | | | | | - Evan D Rosen
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.,Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
| | - Richard T Lee
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.,Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,Harvard Stem Cell Institute and.,Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, Massachusetts, USA
| | - Claude P Lechene
- Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.,Center for NanoImaging, Brigham and Women's Hospital, Cambridge, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Matthew L Steinhauser
- Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.,Center for NanoImaging, Brigham and Women's Hospital, Cambridge, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.,Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,Harvard Stem Cell Institute and
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Harguindey S, Stanciu D, Devesa J, Alfarouk K, Cardone RA, Polo Orozco JD, Devesa P, Rauch C, Orive G, Anitua E, Roger S, Reshkin SJ. Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases. Semin Cancer Biol 2017; 43:157-179. [PMID: 28193528 DOI: 10.1016/j.semcancer.2017.02.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 02/06/2017] [Indexed: 12/27/2022]
Abstract
During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversed proton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, a translational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intracellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cells have never been described in any other disease and now appear to be a specific hallmark of malignancy. As a consequence of this intracellular acid-base homeostatic failure, the attempt to induce cellular acidification using proton transport inhibitors and other intracellular acidifiers of different origins is becoming a new therapeutic concept and selective target of cancer treatment, both as a metabolic mediator of apoptosis and in the overcoming of multiple drug resistance (MDR). Importantly, there is increasing data showing that different ion channels contribute to mediate significant aspects of cancer pH regulation and etiopathogenesis. Finally, we discuss the extension of this new pH-centric oncological paradigm into the opposite metabolic and homeostatic acid-base situation found in human neurodegenerative diseases (HNDDs), which opens novel concepts in the prevention and treatment of HNDDs through the utilization of a cohort of neural and non-neural derived hormones and human growth factors.
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Affiliation(s)
- Salvador Harguindey
- Institute of Clinical Biology and Metabolism, c) Postas 13, 01004 Vitoria, Spain.
| | - Daniel Stanciu
- Institute of Clinical Biology and Metabolism, c) Postas 13, 01004 Vitoria, Spain
| | - Jesús Devesa
- Department of Physiology, School of Medicine, University of Santiago de Compostela, Spain and Scientific Director of Foltra Medical Centre, Teo, Spain
| | - Khalid Alfarouk
- Al-Ghad International Colleges for Applied Medical Sciences, Al-Madinah Al-Munawarah, Saudi Arabia
| | - Rosa Angela Cardone
- Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70125 Bari, Italy
| | | | - Pablo Devesa
- Research and Development, Medical Centre Foltra, Teo, Spain
| | - Cyril Rauch
- School of Veterinary Medicine and Science, University of Nottingham,College Road, Sutton Bonington, LE12 5RD, UK
| | - Gorka Orive
- Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Networking Biomedical Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, SLFPB-EHU, 01006 Vitoria, Spain
| | - Eduardo Anitua
- BTI Biotechnology Institute ImasD, S.L. C/Jacinto Quincoces, 39, 01007 Vitoria, Spain
| | - Sébastien Roger
- Inserm UMR1069, University François-Rabelais of Tours,10 Boulevard Tonnellé, 37032 Tours, France; Institut Universitaire de France, 1 Rue Descartes, Paris 75231, France
| | - Stephan J Reshkin
- Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70125 Bari, Italy
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Morgan A, Mooney K, Mc Auley M. Obesity and the dysregulation of fatty acid metabolism: implications for healthy aging. Expert Rev Endocrinol Metab 2016; 11:501-510. [PMID: 30058918 DOI: 10.1080/17446651.2016.1245141] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The population of the world is aging. In 2010, an estimated 524 million people were aged 65 years or older representing eight percent of the global population. By 2050, this number is expected to nearly triple to approximately 1.5 billion, 16 percent of the world's population. Although people are living longer, the quality of their lives are often compromised due to ill-health. Areas covered: Of the conditions which compromise health as we age, obesity is at the forefront. Over half of the global older population were overweight or obese in 2010, significantly increasing the risk of a range of metabolic diseases. Although, it is well recognised excessive calorie intake is a fundamental driver of adipose tissue dysfunction, the relationship between obesity; intrinsic aging; and fat metabolism is less understood. In this review we discuss the intersection between obesity, aging and the factors which contribute to the dysregulation of whole-body fat metabolism. Expert commentary: Being obese disrupts an array of physiological systems and there is significant crosstalk among these. Moreover it is imperative to acknowledge the contribution intrinsic aging makes to the dysregulation of these systems and the onset of disease.
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Affiliation(s)
- Amy Morgan
- a Department of Chemical Engineering , University of Chester, Thornton Science Park , Chester , UK
| | - Kathleen Mooney
- b Faculty of Health and Social Care , Edge Hill University , Lancashire , UK
| | - Mark Mc Auley
- a Department of Chemical Engineering , University of Chester, Thornton Science Park , Chester , UK
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32
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Hunt SM. Developing a Measure of Quality of Life for Adults with Growth Hormone Deficiency. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/009286159402800102] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Rasmussen LH, Karlsmark T, Avnstorp C, Peters K, Jørgensen M, Jensen LT. Topical Human Growth Hormone Treatment of Chronic Leg Ulcers. Phlebology 2016. [DOI: 10.1177/026835559100600105] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
In a double-blind placebo-controlled trial, 37 patients with chronic leg ulceration were randomized to receive either topical human growth hormone, 1 IU cm −2 ulcer area, 5 d per week, or placebo, in addition to a standard treatment (compression, hydrocolloid dressing). The two groups were broadly similar in age, sex, initial ulcer area and underlying aetiological variables. During the study 18 patients were withdrawn (six in the growth hormone group and 12 in the placebo group; NS). Eight of them did not complete the 2 weeks of treatment necessary to establish a healing rate and were consequently not included in the analyses of healing. During a mean treatment period of 8 weeks, the healing rate was 16% per week (95% confidence interval 8.7 to 23% per week) in the growth hormone group and 3% per week (−3.4 to 8.4% per week) in the placebo group, ( P = 0.02). In 11 patients (61%) in the growth hormone group and two patients (18%) in the placebo group, the ulcer area decreased by 50% during the study ( P = 0.03). The treatment was neither accompanied by side-effects nor signs or symptoms indicating a significant absorption of growth hormone. Further studies are needed to address the dose-response relationship and optimal administration frequency of topical growth hormone in the treatment of chronic leg ulcers.
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Affiliation(s)
| | - Tonny Karlsmark
- Department of Dermatology, Rigshospitalet, University of Copenhagen, Denmark
| | - Christian Avnstorp
- Department of Dermatology, Gentofte Hospital, University of Copenhagen, Denmark
| | - Kurt Peters
- Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Denmark
| | | | - Lars T. Jensen
- Department of Rheumatology Hvidovre Hospital, University of Copenhagen, Denmark
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Milman S, Huffman DM, Barzilai N. The Somatotropic Axis in Human Aging: Framework for the Current State of Knowledge and Future Research. Cell Metab 2016; 23:980-989. [PMID: 27304500 PMCID: PMC4919980 DOI: 10.1016/j.cmet.2016.05.014] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 05/24/2016] [Accepted: 05/26/2016] [Indexed: 12/19/2022]
Abstract
Mutations resulting in reduced signaling of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis are associated with increased life- and healthspan across model organisms. Similar findings have been noted in human cohorts with functional mutations in the somatotropic axis, suggesting that this pathway may also be relevant to human aging and protection from age-related diseases. While epidemiological data indicate that low circulating IGF-1 level may protect aging populations from cancer, results remain inconclusive regarding most other diseases. We propose that studies in humans and animals need to consider differences in sex, pathway function, organs, and time-specific effects of GH/IGF-1 signaling in order to better define the role of the somatotropic axis in aging. Agents that modulate signaling of the GH/IGF-1 pathway are available for human use, but before they can be implemented in clinical studies that target aging and age-related diseases, researchers need to address the challenges discussed in this Review.
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Affiliation(s)
- Sofiya Milman
- Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Division of Geriatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
| | - Derek M Huffman
- Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Nir Barzilai
- Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Division of Geriatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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Roelfsema F, Veldhuis JD. Growth Hormone Dynamics in Healthy Adults Are Related to Age and Sex and Strongly Dependent on Body Mass Index. Neuroendocrinology 2016; 103:335-44. [PMID: 26228064 PMCID: PMC4731317 DOI: 10.1159/000438904] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Accepted: 07/15/2015] [Indexed: 11/19/2022]
Abstract
BACKGROUND Studies on 24-hour growth hormone (GH) secretion are rare. The influences of sex, age, and adiposity are well recognized but generally derived from specific, selected subject groups, not spanning sexes, many age decades, and a range of body weights. OBJECTIVE Our goal was to investigate GH dynamics in a group of 130 healthy adult subjects, both men and women, across 5 age decades as well as a 2.5-fold range of body mass index (BMI) values. METHODS GH was measured by a sensitive immunofluorometric assay. Secretion parameters were quantified by automated deconvolution and relative pattern randomness by approximate entropy (ApEn). RESULTS The median age was 40 years (range 20-77). The median BMI was 26 (range 18.3-49.8). Pulsatile 24-hour GH secretion was negatively correlated with age (p = 0.002) and BMI (p < 0.0001). Basal GH secretion negatively correlated with BMI (p = 0.003) but not with age. The sex- dependent GH secretion (greater in women) was no longer detectable after 50 years of age. Insulin-like growth factor (IGF)-1 levels were lower in women over 50 years of age compared with men of a similar age. ApEn showed an age-related increase in both sexes and was higher in premenopausal and postmenopausal women than in men of comparable age (p < 0.0001). A single fasting GH measurement is not informative of 24-hour GH secretion. CONCLUSIONS BMI dominates the negative regulation of 24-hour GH secretion across 5 decades of age in this up till now largest cohort of healthy adults who underwent 24-hour blood sampling. Sex also impacts GH secretion before the age of 50 years as well as its regularity at all ages. Differences in serum IGF-1 partly depend on the pre- or postmenopausal state. Finally, a single GH measurement is not informative of 24-hour GH secretion.
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Affiliation(s)
- Ferdinand Roelfsema
- Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands
| | - Johannes D. Veldhuis
- Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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Salini V, Vanni D, Pantalone A, Abate M. Platelet Rich Plasma Therapy in Non-insertional Achilles Tendinopathy: The Efficacy is Reduced in 60-years Old People Compared to Young and Middle-Age Individuals. Front Aging Neurosci 2015; 7:228. [PMID: 26696880 PMCID: PMC4674567 DOI: 10.3389/fnagi.2015.00228] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 11/23/2015] [Indexed: 12/15/2022] Open
Abstract
Background: Platelet Rich Plasma (PRP) has shown positive and long-lasting effects in patients with tendinopathies. However, information about age-related differences in the clinical outcome is limited. Aim of this retrospective study was to compare the efficacy of PRP therapy in young and elderly subjects suffering for Achilles tendinopathy. Materials and method: Patients with recalcitrant non-insertional Achilles tendinopathy were enrolled. Clinical (VISA-A) and instrumental (ultrasonography) data were collected at baseline and after 1, 3, 6, and 12 months. PRP injections (once a week for 3 weeks) were performed in sterile conditions and under ultrasound (US) control. Results: Forty-four subjects (29 young: mean age 39.5 ± 6.9; 15 elderly: mean age 61.5 ± 5.3) were retrospectively evaluated. At baseline, no significant differences were observed in the clinical and US parameters. Throughout the whole length of the study, a significant increase of VISA-A score was seen in both groups (from 50.3 ± 8.8 to 76.1 ± 6.6 in the young group, and from 48.7 ± 7.6 to 61.1 ± 9.4 in the elderly group); however, the infra-groups comparison showed better results in young patients, compared to the aged counterpart. Conclusion: Our results show that PRP is less effective in aged people. This finding can be ascribed to several biochemical and biomechanical differences documented in tendons of young and elderly subjects (reduced number and functionality of tenocytes and tenoblasts), which becomes more evident in the long-term tissue healing. However, prospective trials, using different PRP preparations and enrolling a larger number of subjects, are needed to draw more sound and definitive conclusions.
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Affiliation(s)
- Vincenzo Salini
- Orthopaedic and Traumatalogical Clinic, Department of Medicine and Science of Aging, Università degli Studi "G. d'Annunzio" Chieti-Pescara Chieti, Italy
| | - Daniele Vanni
- Orthopaedic and Traumatalogical Clinic, Department of Medicine and Science of Aging, Università degli Studi "G. d'Annunzio" Chieti-Pescara Chieti, Italy
| | - Andrea Pantalone
- Orthopaedic and Traumatalogical Clinic, Department of Medicine and Science of Aging, Università degli Studi "G. d'Annunzio" Chieti-Pescara Chieti, Italy
| | - Michele Abate
- Orthopaedic and Traumatalogical Clinic, Department of Medicine and Science of Aging, Università degli Studi "G. d'Annunzio" Chieti-Pescara Chieti, Italy
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Veldhuis JD, Olson TP, Takahashi PY, Miles JM, Joyner MJ, Yang RJ, Wigham J. Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men. Metabolism 2015; 64:1022-30. [PMID: 26028283 PMCID: PMC4546548 DOI: 10.1016/j.metabol.2015.05.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Revised: 01/21/2015] [Accepted: 05/12/2015] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Exercise evokes pulsatile GH release followed by autonegative feedback, whereas glucose suppresses GH release followed by rebound-like GH release (feedforward escape). Here we test the hypothesis that age, sex steroids, insulin, body composition and physical power jointly determine these dynamic GH responses. METHODS This was a prospectively randomized glucose-blinded study conducted in the Mayo Center for Advancing Translational Sciences in healthy men ages 19-77 years (N=23). Three conditions, fasting/rest/saline, fasting/exercise/saline and fasting/rest/iv glucose infusions, were used to drive GH dynamics during 10-min blood sampling for 6h. Linear correlation analysis was applied to relate peak/nadir GH dynamics to age, sex steroids, insulin, CT-estimated abdominal fat and physical power (work per unit time). RESULTS Compared with the fasting/rest/saline (control) day, fasting/exercise/saline infusion evoked peak GH within 1h, followed by negative feedback 3-5h later. The dynamic GH excursion was strongly (R(2)=0.634) influenced by (i) insulin negatively (P=0.011), (ii) power positively (P=0.0008), and (iii) E2 positively (P=0.001). Dynamic glucose-modulated GH release was determined by insulin negatively (P=0.0039) and power positively (P=0.0034) (R(2)=0.454). Under rest/saline, power (P=0.031) and total abdominal fat (P=0.012) (R(2)=0.267) were the dominant correlates of GH excursions. CONCLUSION In healthy men, dynamic GH perturbations induced by exercise and glucose are strongly related to physical power, insulin, estradiol, and body composition, thus suggesting a network of regulatory pathways.
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Affiliation(s)
- Johannes D Veldhuis
- Endocrine Research Unit, Mayo Clinic College of Medicine, Center for Translational Science Activities.
| | - Thomas P Olson
- Cardiovascular Research, Mayo Clinic, Rochester, MN 55905
| | - Paul Y Takahashi
- Primary Care Internal Medicine, Mayo Clinic, Rochester, MN 55905
| | - John M Miles
- Endocrine Research Unit, Mayo Clinic College of Medicine, Center for Translational Science Activities
| | | | - Rebecca J Yang
- Endocrine Research Unit, Mayo Clinic College of Medicine, Center for Translational Science Activities
| | - Jean Wigham
- Endocrine Research Unit, Mayo Clinic College of Medicine, Center for Translational Science Activities
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The effects of testosterone and insulin-like growth factor 1 on motor system form and function. Exp Gerontol 2015; 64:81-6. [PMID: 25681641 DOI: 10.1016/j.exger.2015.02.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Revised: 01/31/2015] [Accepted: 02/10/2015] [Indexed: 12/25/2022]
Abstract
In this perspective article, we review the effects of selected anabolic hormones on the motoric system and speculate on the role these hormones may have on influencing muscle and physical function via their impact on the nervous system. Both muscle strength and anabolic hormone levels decline around middle age into old age over a similar time period, and several animal and human studies indicate that exogenously increasing anabolic hormones (e.g., testosterone and insulin-like growth factor-1 (IGF-1)) in aged subjects is positively associated with improved muscle strength. While most studies in humans have focused on the effects of anabolic hormones on muscle growth, few have considered the impact these hormones have on the motoric system. However, data from animals demonstrate that administering either testosterone or IGF-1 to cells of the central and peripheral motor system can increase cell excitability, attenuate atrophic changes, and improve regenerative capacity of motor neurons. While these studies do not directly indicate that changes in anabolic hormones contribute to reduced human performance in the elderly (e.g., muscle weakness and physical limitations), they do suggest that additional research is warranted along these lines.
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Jones CM, Boelaert K. The Endocrinology of Ageing: A Mini-Review. Gerontology 2014; 61:291-300. [PMID: 25471682 DOI: 10.1159/000367692] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 08/19/2014] [Indexed: 11/19/2022] Open
Abstract
Significant advances in health and social wellbeing have led to linear gains in life expectancy and an accompanying increase in the burden imposed by age-related morbidities. Complex alterations in hormonal networks which regulate homeostasis and survival may underlie this poor adaptation to later life, as exemplified by an increased fracture risk amongst post-menopausal women. Beyond overt under- or overactivity of hormonal axes, changes in the concentrations of regulatory hormones may also impact on health and disease. Subclinical hyperthyroidism, a disorder characterised by normal thyroxine levels in the presence of decreased thyroid-stimulating hormone, is, for instance, independently associated with an increased risk of atrial fibrillation amongst elderly populations. Both the menopause and subclinical thyroid disease demonstrate the difficulty in reversing endocrine changes in later life, with minimal impact from thyroxine therapy in subclinical hypothyroidism and multiple reports of harm resulting from hormone replacement therapy in peri- and post-menopausal women. Given these findings, strategies to locally regulate hormone bioavailability by altering pre-receptor metabolism may offer greater therapeutic potential in the fight against age-related disease. This review aims to provide an overview of the ageing endocrine system and its potential impact on health and disease in the elderly. It will postulate that strategies to coordinate pre-receptor hormone metabolism and a greater understanding of putative hormonal longevity pathways may offer key new drug targets in the fight against ageing, and will argue against applying the conventional endocrine maxim of 'block and replace' to hormonal changes seen during ageing.
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Affiliation(s)
- Christopher M Jones
- Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK
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Veiga Silva AC, da Rosa MI, Fernandes B, Lumertz S, Diniz RM, dos Reis Damiani MEF. [Factors associated with osteopenia and osteoporosis in women undergoing bone mineral density test]. REVISTA BRASILEIRA DE REUMATOLOGIA 2014; 55:223-8. [PMID: 25440700 DOI: 10.1016/j.rbr.2014.08.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 03/16/2014] [Accepted: 08/17/2014] [Indexed: 10/24/2022] Open
Abstract
The aim of this study was to determine the prevalence of osteopenia and osteoporosis in a female population, that had bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) in a specialized clinic in the south of Brazil. We conducted a cross-sectional study including 1,871 women that performed scans between January and December 2012. We conducted a logistic regression analysis with all independent variables and outcomes (osteopenia, osteoporosis and fracture risk). According to DXA results, 36.5% of women had normal BMD, 49.8% were diagnosed with osteopenia and 13.7% with osteoporosis. Menopause and age over 50 years old were risk factors for osteopenia and osteoporosis while prior hysterectomy and BMI greater than 25 were protective factors. For the outcome of fracture at any site the risk factors were age over 50 years old, osteopenia and osteoporosis (OR = 2.09, 95% CI:1,28-3, 40) and (OR = 2.49, 95% CI:1,65-3, 74), respectively.
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Affiliation(s)
| | | | - Bruna Fernandes
- Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil
| | - Suéli Lumertz
- Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil
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Growth hormone, insulin-like growth factor-1 and the aging brain. Exp Gerontol 2014; 68:76-81. [PMID: 25300732 DOI: 10.1016/j.exger.2014.10.002] [Citation(s) in RCA: 157] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 10/03/2014] [Accepted: 10/06/2014] [Indexed: 10/24/2022]
Abstract
Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan.
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Lygren T, Hansen S, Langberg H, Fjeldborg J, Jacobsen S, Nielsen MO, Schjerling P, Markussen B, Thomsen PD, Berg LC. Serum insulin-like growth factor 1 in the aging horse. Vet Clin Pathol 2014; 43:557-60. [DOI: 10.1111/vcp.12201] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Tone Lygren
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - Sanni Hansen
- Department of Large Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Taastrup Denmark
| | - Henning Langberg
- Department of Public Health; CopenRehab; Section of Social Medicine; Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
| | - Julie Fjeldborg
- Department of Large Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Taastrup Denmark
| | - Stine Jacobsen
- Department of Large Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Taastrup Denmark
| | - Mette O. Nielsen
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - Peter Schjerling
- Department of Orthopedic Surgery; Institute of Sports Medicine; Bispebjerg Hospital and Center for Healthy Aging; Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
| | - Bo Markussen
- Department of Mathematical Sciences; Laboratory of Applied Statistics; Faculty of Science; University of Copenhagen; Copenhagen Denmark
| | - Preben D. Thomsen
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - Lise C. Berg
- Department of Large Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Taastrup Denmark
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Rafael H. Omental transplantation for neurodegenerative diseases. AMERICAN JOURNAL OF NEURODEGENERATIVE DISEASE 2014; 3:50-63. [PMID: 25232510 PMCID: PMC4162586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 08/03/2014] [Indexed: 06/03/2023]
Abstract
Up to date, almost all researchers consider that there is still no effective therapy for neurodegenerative diseases (NDDs) and therefore, these diseases are incurable. However, since May 1998, we know that a progressive ischemia in the medial temporal lobes and subcommissural regions can cause Alzheimer's disease; because, in contrast to this, its revascularization by means of omental tissue can cure or improve this disease. Likewise we observed that the aging process, Huntington's disease, Parkinson's disease, and Amyotrophic lateral sclerosis; all of them are of ischemic origin caused by cerebral atherosclerosis, associated with vascular anomalies and/or environmental chemicals. On the contrary, an omental transplantation on the affected zone can stop and improve these diseases. For these reasons, I believe that NDDs, are wrongly classified as neurodegenerative disorders.
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Pasco JA, Holloway KL, Dobbins AG, Kotowicz MA, Williams LJ, Brennan SL. Body mass index and measures of body fat for defining obesity and underweight: a cross-sectional, population-based study. BMC OBESITY 2014. [PMID: 26217501 PMCID: PMC4511447 DOI: 10.1186/2052-9538-1-9] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND The body mass index (BMI) is commonly used as a surrogate marker for adiposity. However, the BMI indicates weight-for-height without considering differences in body composition and the contribution of body fat to overall body weight. The aim of this cross-sectional study was to identify sex-and-age-specific values for percentage body fat (%BF), measured using whole body dual energy x-ray absorptiometry (DXA), that correspond to BMI 18.5 kg/m(2) (threshold for underweight), 25.0 kg/m(2) (overweight) and 30.0 kg/m(2) (obesity) and compare the prevalence of underweight, overweight and obesity in the adult white Australian population using these BMI thresholds and equivalent values for %BF. These analyses utilise data from randomly-selected men (n = 1446) and women (n = 1045), age 20-96 years, who had concurrent anthropometry and DXA assessments as part of the Geelong Osteoporosis Study, 2001-2008. RESULTS Values for %BF cut-points for underweight, overweight and obesity were predicted from sex, age and BMI. Using these cut-points, the age-standardised prevalence among men for underweight was 3.1% (95% CI 2.1, 4.1), overweight 40.4% (95% CI 37.7, 43.1) and obesity 24.7% (95% CI 22.2, 27.1); among women, prevalence for underweight was 3.8% (95% CI 2.6, 5.0), overweight 32.3% (95% CI 29.5, 35.2) and obesity 29.5% (95% CI 26.7, 32.3). Prevalence estimates using BMI criteria for men were: underweight 0.6% (95% CI 0.2, 1.1), overweight 45.5% (95% CI 42.7, 48.2) and obesity 19.7% (95% CI 17.5, 21.9); and for women, underweight 1.4% (95% CI 0.7, 2.0), overweight 30.3% (95% CI 27.5, 33.1) and obesity 28.2% (95% CI 25.4, 31.0). CONCLUSIONS Utilising a single BMI threshold may underestimate the true extent of obesity in the white population, particularly among men. Similarly, the BMI underestimates the prevalence of underweight, suggesting that this body build is apparent in the population, albeit at a low prevalence. Optimal thresholds for defining underweight and obesity will ultimately depend on risk assessment for impaired health and early mortality.
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Affiliation(s)
- Julie A Pasco
- Epi-Centre for Healthy Ageing, School of Medicine, IMPACT SRC, Deakin University, PO Box 281, Geelong, Victoria 3220 Australia ; NorthWest Academic Centre, The University of Melbourne, St Albans, Victoria Australia
| | - Kara L Holloway
- Epi-Centre for Healthy Ageing, School of Medicine, IMPACT SRC, Deakin University, PO Box 281, Geelong, Victoria 3220 Australia
| | - Amelia G Dobbins
- Epi-Centre for Healthy Ageing, School of Medicine, IMPACT SRC, Deakin University, PO Box 281, Geelong, Victoria 3220 Australia
| | - Mark A Kotowicz
- Epi-Centre for Healthy Ageing, School of Medicine, IMPACT SRC, Deakin University, PO Box 281, Geelong, Victoria 3220 Australia ; NorthWest Academic Centre, The University of Melbourne, St Albans, Victoria Australia
| | - Lana J Williams
- Epi-Centre for Healthy Ageing, School of Medicine, IMPACT SRC, Deakin University, PO Box 281, Geelong, Victoria 3220 Australia
| | - Sharon L Brennan
- Epi-Centre for Healthy Ageing, School of Medicine, IMPACT SRC, Deakin University, PO Box 281, Geelong, Victoria 3220 Australia ; NorthWest Academic Centre, The University of Melbourne, St Albans, Victoria Australia
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Leitner MK, Kautzky-Willer A. [Gender-specific differences in age-associated endocrinology]. Z Gerontol Geriatr 2014; 46:505-10. [PMID: 23780632 DOI: 10.1007/s00391-013-0512-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The endocrine system is intimately involved in modulating lifespan and quality of life. Facing an ever increasing proportion of aged people in the western society, there is great interest in understanding the complex interrelations between increasing age and hormonal regulation. Age-associated endocrinological changes comprise the decline of basal hormonal levels, pulsatile hormone distribution, and activity of hormonal axis, which result in changes in body composition. Men and women experience different age-associated alterations of the hormonal system. Aging per se is a risk factor for diseases like diabetes mellitus type 2, thyroid disorders, osteoporosis, frailty, and sarcopenia. Gender-specific differences with respect to symptoms, interactions, diagnosis, and therapy must be taken into consideration. Current data do not allow a general recommendation for hormonal substitution, neither for women nor for men. New research approaches following a multifactorial pathway are required to elucidate the complexity of age-associated endocrinological changes and to develop gender-specific therapies for endocrinological diseases.
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Affiliation(s)
- M K Leitner
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Gender Medicine Unit, Innere Medizin III, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich
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Vestergaard PF, Hansen M, Frystyk J, Espelund U, Christiansen JS, Jørgensen JOL, Fisker S. Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults. Eur J Endocrinol 2014; 170:229-36. [PMID: 24179101 DOI: 10.1530/eje-13-0661] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Senescent changes in body composition and muscle strength are accompanied by reduced production of GH and IGF1, but the causal relationship remains elusive. We speculate that serum bioactive IGF1, measured by the IGF1 kinase receptor activation assay, is closer related to human physiological ageing than total IGF1 measured by immunoassay. DESIGN We conducted a cross-sectional study in 150 adult males and females, between 20 and 70 years. After an overnight fasting, serum levels of bioactive IGF1, total IGF1 and IGF-binding protein 1 (IGFBP1) and IGFBP3 were assessed. Furthermore, body composition and muscle strength was measured. RESULTS Total IGF1 levels were higher in females (P=0.048). Bioactive IGF1 were identical in males and females (P=0.31), decreasing with age. Total IGF1 tended to decrease more with age compared with bioactive IGF1 (-1.48 vs -0.89 percent/year, P=0.052). Total body fat (TBF) was lower and BMI was higher in males (P<0.001 and P=0.005), and both increased with age. Knee extension and elbow flexion force were higher in males (P=0.001 and P=0.001), but decreased with age in both genders. Total but not bioactive IGF1 was positively correlated to TBF, knee extension and muscle function in males. In multiple linear regression, only age predicted total IGF1, whereas age and IGFBP1 predicted bioactive IGF1. CONCLUSIONS Bioactive IGF1 tends to decrease to a lesser extent than total IGF1 with age and was not correlated with measures of body composition or muscle strength. Therefore, levels of circulating bioactive IGF1 does not appear to be a better biomarker of physiological ageing than total IGF1.
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Affiliation(s)
- Poul Frølund Vestergaard
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark
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Boesen AP, Dideriksen K, Couppé C, Magnusson SP, Schjerling P, Boesen M, Aagaard P, Kjaer M, Langberg H. Effect of growth hormone on aging connective tissue in muscle and tendon: gene expression, morphology, and function following immobilization and rehabilitation. J Appl Physiol (1985) 2014; 116:192-203. [DOI: 10.1152/japplphysiol.01077.2013] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
It is unknown whether loss in musculotendinous tissue during inactivity can be counteracted by growth hormone (GH), and whether GH accelerate rehabilitation in aging individuals. Elderly men (65–75 yr; n = 12) had one leg immobilized 2 wk followed by 6 wk of retraining and were randomly assigned to daily injections of recombinant GH (rhGH; n = 6) or placebo (Plc; n = 6). Cross-sectional area (CSA), muscle strength (MVC), and biomechanical properties of m. quadriceps and patellar tendon were determined. Muscle and tendon biopsies were analyzed for gene expressions (mRNA) of collagen (COL1A1/3A1) and insulin-like growth factors (IGF-1Ea/Ec). Fibril morphology was analyzed by transmission electron microscope (TEM). In tendon, CSA and biomechanical properties did not change following immobilization, but an increase in CSA was found after 6 wk of rehabilitation in both groups. The changes were more pronounced when GH was injected. Furthermore, tendon stiffness increased in the GH group. Muscle CSA declined after immobilization in the Plc but not in the GH group. Muscle CSA increased during retraining, with a significantly larger increase in the GH group compared with the Plc group. Both a time and a group effect were seen for IGF-1Ea/Ec and COL1A1/3A1 mRNA expression in muscle, with a difference between GH and Plc. IGF-1Ea/Ec and COL-1A1/3A1 mRNA expression increased in muscle following immobilization and retraining in subjects receiving GH, whereas an increase in IGF-1Ec mRNA expression was seen in the Plc group only after retraining. In conclusion, in elderly humans, GH seems to have a matrix stabilizing effect during inactivity and rehabilitation by stimulating collagen expression in the musculotendinous tissue and increasing tendon CSA and stiffness.
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Affiliation(s)
- A. P. Boesen
- Department of Ortopaedic Surgery M, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - K. Dideriksen
- Department of Ortopaedic Surgery M, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - C. Couppé
- Department of Ortopaedic Surgery M, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Physical Therapy, Bispebjerg Hospital, Copenhagen, Denmark
| | - S. P. Magnusson
- Department of Ortopaedic Surgery M, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Physical Therapy, Bispebjerg Hospital, Copenhagen, Denmark
| | - P. Schjerling
- Department of Ortopaedic Surgery M, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - M. Boesen
- Department of Radiology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - P. Aagaard
- Institute of Exercise Physiology and Clinical Biomechanics, SDU Muscle Research Cluster (SMRC), University of Southern Denmark, Odense, Denmark; and
| | - M. Kjaer
- Department of Ortopaedic Surgery M, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - H. Langberg
- Department of Ortopaedic Surgery M, Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Public Health, CopenRehab, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Function of GH/IGF-I axis in aging: Multicenter study in 152 healthy elderly subjects with different degrees of physical activity. Aging Clin Exp Res 2014. [DOI: 10.1007/bf03340148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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50
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Abstract
Secretion of growth hormone (GH) and IGF-1 levels decline during advancing years-of-life. These changes (somatopause) are associated with loss of vitality, muscle mass, physical function, together with the occurrence of frailty, central adiposity, cardiovascular complications, and deterioration of mental function. For GH treatment to be considered for anti-aging, improved longevity, organ-specific function, or quality of life should be demonstrable. A limited number of controlled studies suggest that GH supplementation in older men increases lean mass by ∼2 kg with similar reductions in fat mass. There is little evidence that GH treatment improves muscle strength and performance (e.g. walking speed or ability to climb stairs) or quality of life. The GHRH agonist (tesamorelin) restores normal GH pulsatility and amplitude, selectively reduces visceral fat, intima media thickness and triglycerides, and improves cognitive function in older persons. This report critically reviews the potential for GH augmentation during aging with emphasis on men since women appear more resistant to treatment.
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Affiliation(s)
- Fred R Sattler
- Keck School of Medicine, University of Southern California, 2020 Zonal Avenue, IRD Building, Room 434, Los Angeles, CA 90033, USA.
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