Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

In recent, oldest-old adults over 85 years are increasing rapidly. Major geriatric problems such as frailty, fall, osteoporosis, sarcopenia, gait disturbance in this population are higher prevalent and more severe than those in older adults under 85 years. Therefore, strategy to evaluate and manage them with combined medical problems and related impairments should be considered to prepare for super aged society in the near future. We introduced comprehensive geriatric physical performance battery to examine a variety of physical function in multidomains, which can be applied to prescribe exercise, nutrition and medications as single or combined therapy specific to the level of physical function. It would be desirable that modality-specific exercise intervention to prevent from functional decline of oldest-old adults will be integrated with clinical setting. Eccentric biased strengthening exercise is highlighted as an appropriate exercise intervention for sarcopenic oldest-old because of low energy expenditure and utilization of the aged muscle stiffness. Furthermore, specially designed exercise machines enabling them to do exercise are developed for severe deconditioned patients that can't participate in the conventional strengthening exercise. Oldest-old adults are expected to become a major patient group in geriatric medicine sooner or later. Basic principles of management for oldest-old adults are not different from geriatric management of frailty and sarcopenia in general old population. Along with the assessment of the multidomain of physical parameters, multidimensional modality-specific interventions should be developed based on each individual physical profiles.
Adult* ; Aged, 80 and over ; Bias (Epidemiology) ; Energy Metabolism ; Gait ; Humans ; Osteoporosis ; Rehabilitation* ; Sarcopenia

Aging affects metabolism, leading to physiological and functional impairments, and is also related to changes in body composition, including reduced skeletal muscle mass and increased body fat. These changes are correlated with the pathophysiology of sarcopenia, which is defined as age-related loss of skeletal muscle mass and strength. Low testosterone levels are associated with unfavorable body composition changes, and sex hormones decrease with aging. Androgen deficiency, along with lack of exercise and poor nutrition, may be among the modifiable contributors to sarcopenia. Testosterone treatment has been reported to have beneficial effects on muscle mass and function, but the results have been inconsistent. Here, we discuss the correlation between testosterone and muscle mass and function, the impact of testosterone on sarcopenia, and the probable mechanisms underlying these effects.
Adipose Tissue ; Aging ; Body Composition ; Gonadal Steroid Hormones ; Metabolism ; Muscle, Skeletal ; Muscles ; Sarcopenia* ; Testosterone*

PURPOSE: This study was conducted to examine effects of sarcopenic obesity on metabolic syndrome in Korean elders. METHODS: This study is based on the analysis of the Korea National Health and Nutrition Examination Survey (KNHANES) with 1,155 subjects (524 men, and 631 women) aged 60 or older, from 2008 to 2011. Sarcopenia was defined as an appendicular skeletal muscle (ASM), divided by weight (%) of <1 SD (standard deviation) below the sex-specific mean for young adults. Obesity was defined as a total body fat percent (men≥25%, women≥35%). RESULTS: The prevalence of SO (sarcopenic obesity) was 13.3% among men and 22.5% among women. Both sexes showed a higher total body fat percent, and the SMI (skeletal muscle index) was the lowest in the SO group. Metabolic syndrome was highly prevalent in the SO group (52.5% men, 60.4% women). The SO group showed a higher risk for metabolic syndrome (odds ratio men 6.57 [95% CI 5.19~7.27], women 3.89 [95% CI 2.41~6.29]) than the obese group (men 3.14 [95% CI 1.76~4.14], women 2.54 [95% CI 1.38~4.65]). CONCLUSION: SO is a major risk factor for metabolic syndrome in Korean elders. Therefore, a nursing program should be given to the Korean elderly SO group to prevent metabolic syndrome.
Adipose Tissue ; Aged ; Female ; Humans ; Korea* ; Male ; Metabolism ; Muscle, Skeletal ; Nursing ; Nutrition Surveys* ; Obesity* ; Prevalence ; Risk Factors ; Sarcopenia ; Young Adult

BACKGROUND/AIMS: This study was conducted in order to analyze the effects of sarcopenia on age-related osteoarthritis (OA) of the knee in a Korean population. METHODS: All the Korean subjects who visited the Yeungnam University Medical Center Health Promotion Center between 2008 and 2012 in order to undergo a routine medical examination were enrolled. A total of 5,723 young, healthy people (2,959 males, 2,764 females) enrolled as normal subjects and 23,473 subjects (13,006 males and 10,467 females) were included for evaluation of the effects of sarcopenia on OA. There were 266 subjects who followed-up bioelectrical impedance analysis at a 4-year interval. Of 327 subjects enrolled in this study, knees with anteroposterior X-rays were assessed according to the Kellgren-Lawrence (K/L) grade. RESULTS: Skeletal muscle mass index (SMI) and basal metabolic rate (BMR) showed a steady decrease with the advance of age (p < 0.01), but SMI showed strong positive correlation with BMR (r = 0.72, β = 30.96, p < 0.01). During the 4-year interval, BMR showed a significant decrease with aging (p < 0.01), consistently with the decrease of SMI. Knees with normal SMI were prone to be designated as K/L grade 0 or 1; however, subjects with sarcopenia showed a trend toward the higher K/L grade, classified as knee radiological osteoarthritis (ROA) (p < 0.01). CONCLUSIONS: The results of this study may indicate that sarcopenia as age-related loss of skeletal muscle mass is interactively correlated with the presence and severity of age-related OA.
Academic Medical Centers ; Aging ; Basal Metabolism ; Body Composition ; Electric Impedance ; Health Promotion ; Humans ; Knee ; Male ; Muscle, Skeletal* ; Osteoarthritis* ; Sarcopenia

Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines) may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis.
Adipokines ; Adipose Tissue ; Aging ; Appetite ; Atherosclerosis* ; Cardiovascular Diseases ; Energy Intake ; Energy Metabolism ; Glucose ; Inflammation* ; Insulin Resistance* ; Insulin* ; Lipid Metabolism ; Liver ; Muscle, Skeletal ; Obesity ; Prevalence ; Sarcopenia ; Sedentary Lifestyle ; Biomarkers

Sarcopenia (loss of muscle mass and/or strength) frequently complicates liver cirrhosis and adversely affects the quality of life; cirrhosis related liver decompensation and significantly decreases wait-list and post-liver transplantation survival. The main therapeutic strategies to improve or reverse sarcopenia include dietary interventions (supplemental calorie and protein intake), increased physical activity (supervised resistance and endurance exercises), hormonal therapy (testosterone), and ammonia lowering agents (L-ornithine L-aspartate, branch chain amino acids) as well as mechanistic approaches that target underlying molecular and metabolic abnormalities. Besides other factors, hyperammonemia has recently gained attention and increase sarcopenia by various mechanisms including increased expression of myostatin, increased phosphorylation of eukaryotic initiation factor 2a, cataplerosis of α ketoglutarate, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis. Sarcopenia contributes to frailty and increases the risk of minimal and overt hepatic encephalopathy.
Ammonia ; Aspartic Acid ; Fibrosis ; Hepatic Encephalopathy ; Hyperammonemia ; Liver ; Liver Cirrhosis ; Metabolism ; Motor Activity ; Myostatin ; Peptide Initiation Factors ; Phosphorylation ; Proteolysis ; Quality of Life ; Reactive Oxygen Species ; Sarcopenia ; Testosterone

Age-related body composition changes such as sarcopenia and obesity affect functional decline in the elderly. We investigated the relationship between body composition parameters and functional limitation in older Korean adults. We enrolled 242 men and 231 women aged > or = 65 yr from the Korean elderly cohort. We used appendicular skeletal muscle mass (ASM) divided by height2 (ASM/Ht2) and ASM divided by weight (ASM/Wt). The isokinetic strength of knee extensor muscles were measured using an isokinetic device. Functional limitations were assessed using the Short Physical Performance Battery (SPPB) score less than nine. Men within the bottom tertile of ASM/Ht2 confer an increased risk for functional limitation compared with those within the top tertile (OR, 6.24; 95% CI, 1.78-22.0). However, in women, subjects within the lowest ASM/Wt tertile had a higher risk compared with those within the highest tertile instead of ASM/Ht2 (OR, 7.60; 95% CI, 2.25-25.7). Leg muscle strength remained the strong measure even after controlling for muscle mass only in women. Only large waist circumference was positively associated with functional limitation only in women. We might consider a different muscle index to assess functional limitation according to the gender.
Aged ; Aging ; *Body Composition ; Body Mass Index ; Female ; Humans ; Knee/*physiology ; Male ; Muscle Strength/*physiology ; Muscle, Skeletal/physiology ; Obesity/*epidemiology/metabolism ; Republic of Korea/epidemiology ; Sarcopenia/*epidemiology/metabolism ; Sex Factors ; Waist Circumference