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Skeletal muscle is a highly plastic tissue that plays a central role in human health and disease. Aging is associated with a decrease in muscle mass and function (sarcopenia) that is associated with a loss of independence and reduced quality of life. Gut microbiota, the bacteria, archaea, viruses, and eukaryotic microbes residing in the gastrointestinal tract are emerging as a potential contributor to age-associated muscle decline. Specifically, advancing age is characterized by a dysbiosis of gut microbiota that is associated with increased intestinal permeability, facilitating the passage of endotoxin and other microbial products (e.g., indoxyl sulfate) into the circulation. Upon entering the circulation, LPS and other microbial factors promote inflammatory signaling and skeletal muscle changes that are hallmarks of the aging muscle phenotype. This review will summarize existing literature suggesting cross-talk between gut microbiota and skeletal muscle health, with emphasis on the significance of this axis for mediating changes in aging skeletal muscle size, composition, and function.

Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore, we performed a systematic literature review to assess the morbidity and mortality burden of anorexia/appetite loss in older populations. Following PRISMA guidelines, searches were run (1 January 2011 to 31 July 2021) in PubMed, Embase® and Cochrane databases to identify English language studies of adults aged ≥ 65 years with anorexia/appetite loss. Two independent reviewers screened titles, s and full text of identified records against pre‐defined inclusion/exclusion criteria. Population demographics were extracted alongside risk of malnutrition, mortality and other outcomes of interest. Of 146 studies that underwent full‐text review, 58 met eligibility criteria. Most studies were from Europe (n = 34; 58.6%) or Asia (n = 16; 27.6%), with few (n = 3; 5.2%) from the United States. Most were conducted in a community setting (n = 35; 60.3%), 12 (20.7%) were inpatient based (hospital/rehabilitation ward), 5 (8.6%) were in institutional care (nursing/care homes) and 7 (12.1%) were in other (mixed or outpatient) settings. One study reported results separately for community and institutional settings and is counted in both settings. Simplified Nutritional Appetite Questionnaire (SNAQ Simplified, n = 14) and subject‐reported appetite questions (n = 11) were the most common methods used to assess anorexia/appetite loss, but substantial variability in assessment tools was observed across studies. The most commonly reported outcomes were malnutrition and mortality. Malnutrition was assessed in 15 studies, with all reporting a significantly higher risk of malnutrition in older individuals with anorexia/appetite loss (vs. without) regardless of country or healthcare setting (community n = 9, inpatient n = 2, institutional n = 3, other n = 2). Of 18 longitudinal studies that assessed mortality risk, 17 (94%) reported a significant association between anorexia/appetite loss and mortality regardless of either healthcare setting (community n = 9, inpatient n = 6, institutional n = 2) or method used to assess anorexia/appetite loss. This association between anorexia/appetite loss and mortality was observed in cohorts with cancer (as expected) but was also observed in older populations with a range of comorbid conditions other than cancer. Overall, our findings demonstrate that, among individuals aged ≥ 65 years, anorexia/appetite loss is associated with increased risk of malnutrition, mortality and other negative outcomes across community, care home and hospital settings. Such associations warrant efforts to improve and standardize screening, detection, assessment and management of anorexia/appetite loss in older adults.

Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70-89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10-0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. ClinicalsTrials.gov NCT00116194.

AbstractObjectivesTo determine the effectiveness of tai chi interventions compared with aerobic exercise, a current core standard treatment in patients with fibromyalgia, and to test whether the effectiveness of tai chi depends on its dosage or duration.DesignProspective, randomized, 52 week, single blind comparative effectiveness trial.SettingUrban tertiary care academic hospital in the United States between March 2012 and September 2016.Participants226 adults with fibromyalgia (as defined by the American College of Rheumatology 1990 and 2010 criteria) were included in the intention to treat analyses: 151 were assigned to one of four tai chi groups and 75 to an aerobic exercise group.InterventionsParticipants were randomly assigned to either supervised aerobic exercise (24 weeks, twice weekly) or one of four classic Yang style supervised tai chi interventions (12 or 24 weeks, once or twice weekly). Participants were followed for 52 weeks. Adherence was rigorously encouraged in person and by telephone.Main outcome measuresThe primary outcome was change in the revised fibromyalgia impact questionnaire (FIQR) scores at 24 weeks compared with baseline. Secondary outcomes included changes of scores in patient’s global assessment, anxiety, depression, self efficacy, coping strategies, physical functional performance, functional limitation, sleep, and health related quality of life.ResultsFIQR scores improved in all five treatment groups, but the combined tai chi groups improved statistically significantly more than the aerobic exercise group in FIQR scores at 24 weeks (difference between groups=5.5 points, 95% confidence interval 0.6 to 10.4, P=0.03) and several secondary outcomes (patient’s global assessment=0.9 points, 0.3 to 1.4, P=0.005; anxiety=1.2 points, 0.3 to 2.1, P=0.006; self efficacy=1.0 points, 0.5 to 1.6, P=0.0004; and coping strategies, 2.6 points, 0.8 to 4.3, P=0.005). Tai chi treatment compared with aerobic exercise administered with the same intensity and duration (24 weeks, twice weekly) had greater benefit (between group difference in FIQR scores=16.2 points, 8.7 to 23.6, P<0.001). The groups who received tai chi for 24 weeks showed greater improvements than those who received it for 12 weeks (difference in FIQR scores=9.6 points, 2.6 to 16.6, P=0.007). There was no significant increase in benefit for groups who received tai chi twice weekly compared with once weekly. Participants attended the tai chi training sessions more often than participants attended aerobic exercise. The effects of tai chi were consistent across all instructors. No serious adverse events related to the interventions were reported.ConclusionTai chi mind-body treatment results in similar or greater improvement in symptoms than aerobic exercise, the current most commonly prescribed non-drug treatment, for a variety of outcomes for patients with fibromyalgia. Longer duration of tai chi showed greater improvement. This mind-body approach may be considered a therapeutic option in the multidisciplinary management of fibromyalgia.Trial registrationClinicalTrials.gov NCT01420640.

Purpose This longitudinal study examined the major physiological mechanisms that determine the age-related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~3 years of follow-up, mobility-limited older adults (mean age: 77.2 ± 4, n  = 22, 12 females) would have significantly greater reductions in leg extensor muscle power compared to healthy older adults (74.1 ± 4, n  = 26, 12 females). Methods Mid-thigh muscle size and composition were assessed using computed tomography. Neuromuscular activation was quantified using surface electromyography and vastus lateralis single muscle fibers were studied to evaluate intrinsic muscle contractile properties. Results At follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: −8.5 % vs. healthy older: −8.8 %, P  > 0.8. Mobility-limited elders had significant reductions in muscle size (−3.8 %, P  < 0.01) and strength (−5.9 %, P  < 0.02), however, these parameters were preserved in healthy older ( P  ≥ 0.7). Neuromuscular activation declined significantly within healthy older, but not in mobility-limited participants. Within both groups, the cross-sectional areas of type I and IIA muscle fibers were preserved while substantial increases in single fiber peak force (>30 %), peak power (>200 %) and unloaded shortening velocity (>50 %) were elicited at follow-up. Conclusion Different physiological mechanisms contribute to the loss of lower extremity muscle power in healthy older and mobility-limited older adults. Neuromuscular changes may be the critical early determinant of muscle power deficits with aging. In response to major whole muscle decrements, major compensatory mechanisms occur within the contractile properties of surviving single muscle fibers in an attempt to restore overall muscle power and function with advancing age.

Background The Sarcopenia and Quality of Life (SarQoL) questionnaire is recognized as the only disease‐specific patient‐reported outcome measure (PROM) for assessing sarcopenia‐related HRQoL. This systematic review and meta‐analysis aimed to provide a quantitative summary of all evidence reported on the reliability, validity, responsiveness and floor/ceiling effects of SarQoL in older adults. Methods Following PRISMA‐COSMIN guidelines, a systematic search for studies evaluating the psychometric properties of SarQoL (i.e., reliability, validity, responsiveness and floor and ceiling effects) in older people was conducted on MEDLINE (via OVID), PsycINFO, Scopus and EMBASE. Studies published between 2013 and November 2024 using a consensual definition of sarcopenia were included. Study selection and data extraction were made by two independent reviewers. A random‐effects model meta‐analysis was applied. PROSPERO registration: CRD42024546880. Results From 411 studies identified by the search strategy, 25 fulfilled the inclusion criteria, including 4585 community‐dwelling individuals, of which 1311 were diagnosed as sarcopenic. SarQoL demonstrated high reliability (pooled Cronbach's alpha values consistently exceeding 0.80) and excellent test–retest reliability (pooled ICC = 0.98). Construct validity was confirmed with strong convergent correlations (pooled r > 0.54) with related dimensions of generic SF‐36 and EQ‐5D and weaker divergent correlations (pooled r < 0.47). Responsiveness, evaluated in two studies using different methodologies, supported the ability of SarQoL to detect meaningful changes in HRQoL. The certainty of evidence was rated as high for reliability, validity and responsiveness. Conclusion This meta‐analysis consolidates a decade of evidence and confirms the strong psychometric properties of SarQoL, with a high level of evidence.

Senescence is a cell fate that contributes to multiple aging-related pathologies. Despite profound age-associated changes in skeletal muscle (SkM), whether its constituent cells are prone to senesce has not been methodically examined. Herein, using single cell and bulk RNA-sequencing and complementary imaging methods on SkM of young and old mice, we demonstrate that a subpopulation of old fibroadipogenic progenitors highly expresses together with multiple senescence-related genes and, concomitantly, exhibits DNA damage and chromatin reorganization. Through analysis of isolated myofibers, we also detail a senescence phenotype within a subset of old cells, governed instead by . Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.

Executive functions underlie self-regulation and are thus important for physical activity and adaptation to new situations. The aim was to investigate, if yearlong physical and cognitive training (PTCT) had greater effects on physical activity among older adults than physical training (PT) alone, and if executive functions predicted physical activity at baseline, after six (6m) and twelve months (12m) of the interventions, one-year post-intervention follow-up and an extended follow-up during COVID-19 lockdown. Data from a single-blinded, parallel-group randomized controlled trial (PASSWORD-study, ISRCTN52388040) were utilized. Participants were 70-85 years old community-dwelling men and women from Jyväskylä, Finland. PT (n = 159) included supervised resistance, walking and balance training, home-exercises and self-administered moderate activity. PTCT (n = 155) included PT and cognitive training targeting executive functions on a computer program. Physical activity was assessed with a one-item, seven-scale question. Executive functions were assessed with color-word Stroop, Trail Making Test (TMT) B-A and Letter Fluency. Changes in physical activity were modeled with multinomial logistic models and the impact of executive functions on physical activity with latent change score models. No significant group-by-time interaction was observed for physical activity (p>0.1). The subjects were likely to select an activity category higher than baseline throughout the study (pooled data: B = 0.720-1.614, p<0.001-0.046). Higher baseline Stroop predicted higher physical activity through all subsequent time-points (pooled data: B = 0.011-0.013, p = 0.015-0.030). Higher baseline TMT B-A predicted higher physical activity at 6m (pooled data: B = 0.007, p = 0.006) and during COVID-19 (B = 0.005, p = 0.030). In the PT group, higher baseline Letter Fluency predicted higher physical activity at 12m (B = -0.028, p = 0.030) and follow-up (B = -0.042, p = 0.002). Cognitive training did not have additive effects over physical training alone on physical activity, but multicomponent training and higher executive function at baseline may support adaptation to and maintenance of a physically active lifestyle among older adults.

Background Whether physical activity can reduce cognitive frailty—a relatively new “compound” phenotype proposed in 2013—and whether the effect of physical activity differs based on levels of inflammation are unknown. Therefore, this study aimed to evaluate the effect of physical activity on cognitive frailty and whether baseline interleukin-6 (IL-6) levels modified this effect. Methods We used data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter, single-blinded randomized trial conducted at eight US field centers between February 2010 and December 2013. The main outcome was cognitive frailty at 24 months, expressed as an ordinal variable based on the six combinations of its two components: frailty (non-frail, pre-frail, and frail) and mild cognitive impairment (yes, no). Frailty and cognition were assessed by the Study of Osteoporotic Fractures (SOF) index and the Modified Mini-Mental State Examination (3MSE) scale, respectively. Plasma IL-6 was measured at baseline. Of the 1635 original randomized sedentary participants (70–89 years), this study included 1298 participants with data on both cognitive frailty and IL-6 assessments at baseline. Results After adjusting for field center, sex, and baseline levels of cognitive frailty, the ordinal logistic regression model revealed that participants in the physical activity group had 21% lower odds (odds ratio, 0.79; 95% confidence interval, 0.64–0.98) of worsening cognitive frailty over 24 months than those in the health education group. The effect of physical activity on cognitive frailty did not differ according to baseline IL-6 levels ( P for interaction = 0.919). The results did not change after additional adjustment for IL-6 subgroups and the inverse probability of remaining in the study. Comparable results were observed according to age, sex, ethnicity/race, and short physical performance battery score ( P for interaction = 0.835, 0.536, 0.934, and 0.458, respectively). Conclusions A 24-month structured, moderate-intensity physical activity program reduced cognitive frailty compared with a health education program in sedentary older persons, and this beneficial effect did not differ according to baseline levels of inflammatory biomarker IL-6. These findings suggest that the new cognitive frailty construct is modifiable and highlight the potential of targeting cognitive frailty for promoting healthy aging. Trial registration Clinicaltrials.gov, NCT01072500

Musculoskeletal disorders are common among older people. Preventive strategies require understanding of age-related changes in strength, function and body composition, including how they interrelate. We have described, and examined associations between, 9-year changes in these parameters among 2917 Health, Aging and Body Composition Study participants (aged 70–79 years). Appendicular lean mass (ALM), whole body fat mass and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. For each characteristic annualised percentage changes were calculated; measures of conditional change (independent of baseline) were derived and their interrelationships were examined using Pearson correlations; proportion of variance at 9-year follow-up explained by baseline level was estimated; and mean trajectories in relation to age were estimated using linear mixed models. Analyses were stratified by sex. Median [lower quartile, upper quartile] annual percentage declines were grip strength (1.5 [0.0, 2.9]), gait speed (2.0 [0.6, 3.7]), ALM (0.7 [0.1, 1.4]), fat mass (0.4 [− 1.1, 1.9]) and hip BMD (0.5 [0.0, 1.1]). Declines were linear for ALM and accelerated over time for other characteristics. Most conditional change measures were positively correlated, most strongly between ALM, fat mass and hip BMD ( r  > 0.28). Proportion of variation at follow-up explained by baseline was lower for grip strength and gait speed (39–52%) than other characteristics (69–86%). Strength and function declined more rapidly, and were less correlated between baseline and follow-up, than measures of body composition. Therefore, broader intervention strategies to prevent loss of strength and function in later life are required as those targeting body composition alone may be insufficient.