• aging
• cell biology
• circadian rhythms
• human
• transcriptomics

• Humans
• Circadian Rhythm/physiology
• Adult
• Aged
• Aging/physiology
• Fibroblasts/metabolism
• Male
• Female
• Gene Expression Regulation
• CLOCK Proteins/genetics
• CLOCK Proteins/metabolism
• Cells, Cultured
• Serum
• Age Factors

• UL1 TR001878 NCATS NIH HHS
• T32 NS105607 NINDS NIH HHS
• NIH NS48471 NINDS NIH HHS
• 5UL1TR001878 NCRR NIH HHS
• R01 NS048471 NINDS NIH HHS
• R00 HL147212 NHLBI NIH HHS
• Gilliam Fellowship Howard Hughes Medical Institute
• R37 NS048471 NINDS NIH HHS
• Investigator Howard Hughes Medical Institute
• R00HL147212 NHLBI NIH HHS
• P30 DK019525 NIDDK NIH HHS
• T32-NS105607 NINDS NIH HHS
• R56 NS048471 NINDS NIH HHS
• National Center for Research Resources
• National Heart, Lung, and Blood Institute
• National Institute of Neurological Disorders and Stroke

• Ageing
• Bile acids
• Glucose and lipid metabolism
• Gut microbiota
• Takeda G protein-coupled receptor 5
• farnesoid X receptor

• Humans
• Bile Acids and Salts/metabolism
• Bile Acids and Salts/biosynthesis
• Aging/metabolism
• Animals
• Receptors, Cytoplasmic and Nuclear/metabolism
• Metabolic Diseases/metabolism

• National Key Research and Development Program of China
• National Natural Science Foundation of China

• cardiovascular disease risk
• cholesterol homeostasis
• dietary cholesterol
• eggs
• lipid metabolism

• Humans
• Cholesterol, Dietary/adverse effects
• Cardiovascular Diseases
• Health Status

There are strong association between remnant cholesterol (RC)/non-high density lipoprotein cholesterol (NHDL-C) and increase cardiovascular (CV) risk. The aim of present study was to investigate the association between target lipid parameters (RC and NHDL-C) and the risk of CV mortality in general population.

Data set from an open database—National Health and Nutrition Examination Surveys (NHANES) 2003–2014 were extracted (n = 14992). Kaplan-Meier, multivariable COX regression, and restricted cubic spline (RCS) parameters.

Compared to the lowest quartile, RC (adjusted hazard ratio [HR] = 1.63 95%CI 1.05–2.52, P for trend = 0.037) and triglycerides (TG: Model 3: HR = 1.69 95%CI 1.10–2.60, P for trend = 0.049) in the highest quartile were independently associated with the increased cardiovascular mortality, while NHDL-C and apolipoprotein B (ApoB) in adjusted models did not show association (P for trend >0.05). In addition, RCS regression demonstrated that RC (P for nonlinearity = 0.011) and TG (P for nonlinearity = 0.010) levels had a similar J-shape association with CV mortality. Threshold effect analysis showed that when RC ≤ 29.3 mg/dL, the level of RC and CV mortality risk were positively correlated.

Our findings suggest high RC levels are associated with an increased risk of CV mortality, which support that the integration of TG-rich lipoproteins parameters in risk assessment might optimize the identification and management of selected population.

Toll-like receptor 4 (TLR4) is a pattern recognition receptor of the innate immune system. TLR4 contributes to many aging-related chronic diseases. However, whether TLR4 is involved in cardiovascular injury during the aging process has not been investigated.

The effects of TLR4 on the cardiovascular system of aged mice were investigated in TLR4^−/− mice. An intraperitoneal glucose tolerance test (IPGTT) and insulin sensitivity test (IST) were conducted to evaluate global insulin sensitivity. Echocardiography was used to measure cardiac structure and performance. An isolated artery ring assay was used to measure the vasodilator function of the thoracic aorta. The inflammatory response was reflected by the serum concentration of cytokines.

TLR4 expression increased in the hearts and aortas of mice in an age-dependent manner. Loss of TLR4 increased insulin sensitivity in aged mice. Moreover, loss of TLR4 improved cardiac performance and endothelium-dependent vascular relaxation in aged mice. Importantly, the increases in serum inflammatory cytokines and oxidative stress in the heart and aorta were also inhibited by TLR4 deficiency.

In summary, loss of TLR4 improved cardiac performance and endothelium-dependent vascular relaxation in aged mice. The reduced inflammatory responses and oxidative stress may be the reason for the protective effects of TLR4 deficiency during aging. Our study indicates that targeting TLR4 is a potential therapeutic strategy for preventing aging-related cardiovascular disease.

More than twenty years ago, knowledge about the importance of cholesterol absorption and the potential therapeutic effect of its inhibition led to the discovery and clinical application of the first and only cholesterol absorption inhibitor to date – ezetimibe. Since then, ezetimibe has become a well-recognized player in lipid-lowering therapy. Recent findings of IMPROVE-IT and EWTOPIA 75 imply that elderly patients over the age of 75 years in particular benefit from ezetimibe. This review summarizes the evidence, discusses the possible underlying pathophysiological mechanisms and calls for a change in future dyslipidemia guidelines.

• Cholesterol
• Cholesterol absorption
• Cholesterol synthesis
• Ezetimibe
• Elderly

• health state profile
• multimorbidity
• polypharmacy
• statins

• Aging
• Bile acid
• Diabetes
• Hypercholesterolaemia
• Obesity
• Probiotics

• natural aging
• inflammaging
• immune system
• hscrp
• il-6

• Adult
• Age Factors
• Aged
• Aging/physiology
• Biomarkers/analysis
• C-Reactive Protein/analysis
• Cholesterol/blood
• Female
• Humans
• Immunosenescence/physiology
• Inflammation/blood
• Interleukin-6/blood
• Male
• Middle Aged
• Oxygen Consumption/physiology
• Sex Factors
• Triglycerides/blood
• Tumor Necrosis Factor-alpha/blood
• Young Adult

• aging
• cardiovascular risk
• frailty
• hypercholesterolemia
• lipid-lowering agents

• Hypertension
• anthropometric indicators
• hematological parameters
• lipid profiles

Chronic inflammation and abnormal cholesterol metabolism are involved in the pathogenesis of gallbladder stone disease (GSD) and that of prostate cancer in experimental studies. We assessed the association between GSD and prostate cancer in this population-based study.

The cumulative incidence of prostate cancer (log-rank test: P <.001) and the risk of prostate cancer (1.64 vs 1.14 per 10 000 person-y, adjusted hazard ratio [aHR] = 1.30, 95% confidence interval [CI] = 1.22-1.39) were greater in the patients with GSD than in those without GSD. Furthermore, the risk of prostate cancer increased with the time of follow-up after a diagnosis of GSD, particularly after 9 years of follow-up (aHR = 1.95, 95% CI = 1.74-2.19).

We identified 9496 patients who were diagnosed with GSD between 1998 and 2011 from Taiwan's Longitudinal Health Insurance Database 2000 as the study cohort. We randomly selected 37 983 controls from the non-GSD population and used frequency matching by age, sex, and index year for the control cohort. All patient cases were followed until the end of 2011 to measure the incidence of prostate cancer.

GSD is associated with an increased risk of prostate cancer, and the risk increases with the time of follow-up after a diagnosis of GSD.

• gallbladder stone disease
• metabolic disorder
• prostate cancer

• Aged
• Aged, 80 and over
• Female
• Hospitalization
• Humans
• Hypolipidemic Agents/therapeutic use
• Logistic Models
• Male
• Polypharmacy
• Prevalence

• APOE genotype
• Campesterol
• Cholestanol
• Cholesterol homeostasis
• Desmosterol
• Sitosterol

The purpose of this article review is to update what is known about the role of diet on non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common cause of chronic liver disease in the developed world and is considered to be a spectrum, ranging from fatty infiltration of the liver alone (steatosis), which may lead to fatty infiltration with inflammation known as non alcoholic steatohepatitis While the majority of individuals with risk factors like obesity and insulin resistance have steatosis, only few people may develop steatohepatitis. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Weight loss alone by dietary changes has been shown to lead to histological improvement in fatty liver making nutrition therapy to become a cornerstone of treatment for NAFLD. Supplementation of vitamin E, C and omega 3 fatty acids are under consideration with some conflicting data. Moreover, research has been showed that saturated fat, trans-fatty acid, carbohydrate, and simple sugars (fructose and sucrose) may play significant role in the intrahepatic fat accumulation. However, true associations with specific nutrients yet to be clarified.

• Diet
• Non-alcoholic fatty acids
• Fatty acids
• Obesity
• Insulin resistance

• Adipose tissue
• Aortic valve sclerosis
• Arrhythmia
• Atherosclerosis
• Autonomic dysfunction
• Cirrhosis
• Dementia
• Falls
• Frailty
• Hepatocellular carcinoma
• Microbiota
• Nuclear receptors
• Pathogenesis
• Sarcopenia
• Treatment

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Aging/metabolism
• Cardiovascular Diseases/epidemiology
• Comorbidity
• Dementia/epidemiology
• Frail Elderly
• Geriatric Assessment
• Host-Pathogen Interactions
• Humans
• Intestines/microbiology
• Life Style
• Middle Aged
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/physiopathology
• Non-alcoholic Fatty Liver Disease/therapy
• Polypharmacy
• Prognosis
• Risk Assessment
• Risk Factors
• Sarcopenia/epidemiology

Obesity, from children to the elderly, has increased in the world at an alarming rate over the past three decades, implying long-term detrimental consequences for individual’s health. Obesity and aging are known to be risk factors for metabolic disorder development, insulin resistance and inflammation, but their relationship is not fully understood. Prevention and appropriate therapies for metabolic disorders and physical disabilities in older adults have become a major public health challenge. Hence, the aim of this study was to evaluate inflammation markers, biochemical parameters and glucose homeostasis during the obese-aging process, to understand the relationship between obesity and health span during the lifetime. In order to do this, the monosodium glutamate (MSG) obesity mice model was used, and data were evaluated at 4, 8, 12, 16 and 20 months in both female and male mice. Our results showed that obesity was a major factor contributing to premature alterations in MSG-treated mice metabolism; however, at older ages, obesity effects were attenuated and MSG-mice became more similar to normal mice. At a younger age (four months old), the Lee index, triglycerides, total cholesterol, TNF-α and transaminases levels increased; while adiponectin decreased and glucose tolerance and insulin sensitivity levels were remarkably altered. However, from 16 months old-on, the Lee index and TNF-α levels diminished significantly, while adiponectin increased, and glucose and insulin homeostasis was recovered. In summary, MSG-treated obese mice showed metabolic changes and differential susceptibility by gender throughout life and during the aging process. Understanding metabolic differences between genders during the lifespan will allow the discovery of specific preventive treatment strategies for chronic diseases and functional decline.