The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences

BackgroundAge-related muscle dysfunction is a major contributor to disability, frailty, and poor clinical outcomes in older adults. Muscle mass and strength provide limited insight into the multifactorial nature of muscular decline. Skeletal Muscle Function Deficit (SMFD) framework integrates multiple domains muscle mass, quality, strength, and power to capture a broader spectrum of age-related muscle dysfunction. ObjectiveTo develop and validate a composite SMFD score and evaluate its associat...

ObjectiveExamine the association of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults. MethodsCross-sectional data from 829 older adults [≥]70 years was used. Total abdominal, subcutaneous, and visceral AT; and thigh muscle fat infiltration (MFI) was quantified by MRI. SM mitochondrial energetics were characterized using in vivo 31P-MRS (ATPmax) and ex vivo high-resolution respirometry (maximal oxidative phosphorylation (OXPHOS)). ActivPal was ...

BackgroundGait adaptability, defined as the ability to adjust walking performance to environmental challenges, likely reflects complex interactions among the central nervous system (CNS) and other physiological systems, however, the drivers of lower gait adaptability in older adults are poorly understood. MethodsWe applied a Bayesian network framework to quantify multisystem interactions contributing to percent change in gait speed (%GSC) on transition from even to uneven surface in 159 older a...

Dopamine (DA) in the central nervous system is considered a master regulator of mobility performance and vigor, but its mechanistic relationship with skeletal muscle energetics is unclear. We tested the cross-sectional association of striatal DA and skeletal muscle mitochondrial function in 146 older adults participating in the Study of Muscle, Mobility and Aging (75.4 years old, 54% women). Striatal DA was measured using (+)-a-[11C] dihydrotetrabenazine (DTBZ) PET imaging for the limbic, sensor...

BackgroundSkeletal muscle energetics decline with age, and physical activity (PA) has been shown to counteract these declines in older adults. Yet, many studies were based on self-reported PA or structured exercise interventions. We examined the associations of objective daily PA and sedentary behavior (SB) with skeletal muscle energetics and also compared with self-reported PA and SB. We also explored the extent to which PA would attenuate the associations of age with muscle energetics. Method...

Recent evidence suggests that grip strength is a critical biomarker of brain, muscle, and metabolic aging. Presently, neuromuscular properties related to individual motor unit firing properties have not been explored in the context of grip strength assessments in older adults. The purpose of this investigation was to examine the intra- and intersession reliability of linear and exponential regression model coefficients derived from motor unit (MU) peak firing rates (PFRs) and action potential am...

BackgroundFrailty is a common geriatric syndrome characterized by increased vulnerability to stressors, reduced physiological reserves and heightened vulnerability and. It is also associated with adverse health outcomes. Given its complex phenotypes and underlying pathophysiology, there is a pressing need for robust, multidimensional biomarkers of frailty to advance personalized care. The objective of this study was to identify serum metabolomics signatures associated with different frailty phen...

BackgroundPhysical performance tests are predictive of mortality and have been proposed for screening for certain health conditions (e.g., sarcopenia); however, the diagnostic screening and prognostic value of physical performance tests has primarily been studied in age-limited or disease-specific cohorts. In this study, we sought to identify the most salient characteristics associated with three lower quarter balance and strength tests in a deeply phenotyped cohort of community-dwelling adults....

AimSarcopenia has been associated with a decrease in masseter muscle (MM) thickness in high-risk older populations. However, the relationship to sarcopenia and determinants of MM volume (MMV) in the general older population remain unclear. MabethodIn a cross-sectional study of 1484 older adults of Tokyo, we evaluated MMV using 3D MRI scanning, appendicular skeletal muscle mass (ASMM), handgrip strength, dietary intake, smoking, insulin-like growth factor 1 (IGF-1) levels, and the ACTN3 R577X po...

OBJECTIVEEmerging evidence shows that perceived fatigability--the quantification of vulnerability to fatigue in relation to specific intensity and duration of activities--may be associated with cognitive function. We sought to quantify associations with multiple domains of cognitive function and the role of physical activity (PA). METHODSSOMMA participants completed the Pittsburgh Fatigability Scale (PFS) Physical and Mental subscales (each range 0-50; higher scores=greater fatigability) and th...

BackgroundThe impact of common cardiovascular medications on sarcopenia in older persons is unclear. The aim of this population-based cohort study was to investigate the relationship between long-term intake of statins and renin-angiotensin-system inhibitors (RASi), i.e. angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), and established muscle mass and function parameters. MethodsCommunity dwelling older adults (n=1,083, 52% women, 68.3 {+/-} 3.5 years at ba...

BackgroundKetone bodies are metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on the inflammatory and metabolic aging pathways underpinning frailty in in vivo models. Ketone esters (KEs) are compounds that induce hyperketonemia without dietary changes and that may impact physical and cognitive function in young adults. The functional effects of KEs have not been studied in older adults. ObjectivesOur long-term goal is to examine if KEs modulate aging biolo...

PurposeWe have recently demonstrated that dietary nitrate, a source of nitric oxide via the enterosalivary pathway, can improve muscle contractile function in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. MethodsA randomized, double-blind, placebo-controlled crossover study was performed to determine the effects of ingesti...

BackgroundFrailty is a geriatric syndrome characterized by chronic inflammation and metabolic insufficiency that creates vulnerability to poor outcomes with aging. We hypothesize that geroscience interventions, which target mechanisms of aging, could ameliorate frailty. Metabolites such as ketone bodies are candidate geroscience interventions, having pleiotropic effects on inflammo-metabolic aging mechanisms. Ketone esters (KEs) induce ketosis without dietary changes, but KEs have not been studi...

Primary sarcopenia is a progressive, age-related decline of skeletal muscle strength, size, and quality, the socio-economic and health impacts of which are set to increase due to global ageing. Despite differences in the physiology of female and male skeletal muscle being well characterised, their alteration with age is less clear. Here we report a striking sexual dimorphism in arm muscle ageing in 478,438 UK Biobank participants aged 40-82 yr. Although the sex difference in age-related arm musc...

Autophagy is an essential component of proteostasis and a key pathway in aging. Identifying associations between autophagy gene expression patterns in skeletal muscle and physical performance outcomes would further our knowledge of mechanisms related with proteostasis and healthy aging. Muscle biopsies were obtained from participants in the Study of Muscle, Mobility and Aging (SOMMA). For 575 participants, RNA was sequenced and expression of 281 genes related to autophagy regulation, mitophagy a...

Background & AimThe current study examined cross-sectional and longitudinal associations between nocturia and frailty in a cohort of men and women aged 60 years and older, as evidence on this topic was lacking. MethodsBaseline and follow-up data from the Berlin Aging Study II (n=1671) assessed on average 7.1 (IQR 6.2-8.7) years apart were analyzed. Self-reported nocturia was dichotomized into </[&ge;] 2 micturitions per night, and frailty was assessed using the Fried Frailty Phenotype. Covariab...

BackgroundMusculoskeletal pain frequently accompanies the development of mobility disability and falls in old age. To better understand this, we aimed to quantify the impact of different pain measures--recalled pain and movement-evoked pain--on 400-meter walk and stair climb time in older adults participating in the Study of Muscle, Mobility and Aging (SOMMA). MethodsIn SOMMA (N=879, age=76.3 {+/-} 5.0 years, 59% women, 84% Non-Hispanic White), participants completed usual pace 400m walk (avg=6...

BackgroundBody composition strongly influences clinical outcomes in older adults, yet body mass index (BMI) lacks discriminatory power, and standard tools such as bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry are not routinely accessible. Deep learning enables scalable, opportunistic assessment of body composition from chest radiographs (CXRs), one of the most widely available imaging modalities. Methods and FindingsUsing the Inception-V3 architecture, we developed a ...

ObjectivesSarcopenia is characterized by the progressive loss of muscle mass and strength and poses significant health risks, particularly for older adults. Recent studies have focused on hospitalization-related sarcopenia--a rapid decline in muscle mass and strength during hospitalization--that has emerged as a critical prognostic factor. This screening review aimed to examine the prevalence of hospitalization-related sarcopenia and risk factors. MethodsThis scoping review was conducted follow...