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Background: Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to offset these declines in older adults. Yet, many studies reporting these effects were based on self-reported PA or structured exercise interventions. Therefore, we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior (SB) with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics. Methods: As part of the Study of Muscle, Mobility and Aging, enrolled older adults (n = 879), 810 (age = 76.4 ± 5.0 years old, mean ± SD; 58% women) had maximal muscle oxidative capacity measured ex vivo via high-resolution respirometry of permeabilized myofibers (maximal oxidative phosphorylation (maxOXPHOS)) and in vivo by 31phosphorus magnetic resonance spectroscopy (maximal adenosine triphosphate (ATPmax)). Accelerometry-measured sedentary behavior, light activity, and moderate-to-vigorous PA (MVPA) were assessed using a wrist-worn ActiGraph GT9X over 7 days. Self-reported sedentary behavior, MVPA, and all PA were assessed with the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire. Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics, as well as the attenuation of the age/muscle energetics association by MVPA and sedentary behavior. As a sensitivity analysis, we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics. Results: Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s × mg) higher maxOXPHOS and 0.012 mM/s higher ATPmax after adjusting for age, site/technician, and sex (p < 0.05). Light activity was not associated with maxOXPHOS or ATPmax. Meanwhile, every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s × mg lower maxOXPHOS and 0.006 mM/s lower ATPmax (p < 0.05). Only associations with ATPmax held after further adjusting for socioeconomic status, body mass index, lifestyle factors, and multimorbidity. CHAMPS MVPA and all PA yielded similar associations with maxOXPHOS and ATPmax (p < 0.05), but sedentary behavior did not. Higher activPAL step count was associated with higher maxOXHPOS and ATPmax (p < 0.05), but time spent in sedentary behavior was not. Additionally, age was significantly associated with muscle energetics for men only (p < 0.05); adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATPmax by 58% in men. Conclusion: More time spent in accelerometry-measured or self-reported daily PA, especially MVPA, was associated with higher skeletal muscle energetics. Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics. Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.

Abstract Background Unhealthy lifestyle behaviours such as smoking, high alcohol consumption, poor diet or low physical activity are associated with morbidity and mortality. Public health guidelines provide recommendations for adherence to these four factors, however, their relationship to the health of older people is less certain. Methods The study involved 11,340 Australian participants (median age 7.39 [Interquartile Range (IQR) 71.7, 77.3]) from the ASPirin in Reducing Events in the Elderly study, followed for a median of 6.8 years (IQR: 5.7, 7.9). We investigated whether a point-based lifestyle score based on adherence to guidelines for a healthy diet, physical activity, non-smoking and moderate alcohol consumption was associated with subsequent all-cause and cause-specific mortality. Results In multivariable adjusted models, compared to those in the unfavourable lifestyle group, individuals in the moderate lifestyle group (Hazard Ratio (HR) 0.73 [95% CI 0.61, 0.88]) and favourable lifestyle group (HR 0.68 [95% CI 0.56, 0.83]) had lower risk of all-cause mortality. A similar pattern was observed for cardiovascular related mortality and non-cancer/non-cardiovascular related mortality. There was no association of lifestyle with cancer-related mortality. Conclusions In a large cohort of initially healthy older people, reported adherence to a healthy lifestyle is associated with reduced risk of all-cause and cause-specific mortality. Adherence to all four lifestyle factors resulted in the strongest protection.

Abstract In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0–29.9 kg/m2 [HR25-29.9 vs 21–24.9 kg/m 2: 0.85; 95% CI, 0.73–1.00] while the highest risk was in those who were underweight [HRBMI

Abstract Background The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health‐related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. Methods White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4–6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength

Abstract Background Older informal caregivers are prone to sedentary behavior and obesity. With great caregiving burdens and frequent physical and mental distress, older informal caregivers may have low adherence and poor results in behavioral intervention for weight management. This study examined whether overweight or obese older informal caregivers could benefit from a behavioral weight management program as much as non-caregivers. Methods The Mobility and Vitality Lifestyle Program (MOVE UP) was a pre-post, community-based, 13-month lifestyle intervention study to help older adults improve physical function performance and lose weight. We identified a subset of informal caregivers (n = 29) and non-caregivers (n = 65) from the MOVE UP participants retrospectively. Changes in lower extremity function, weight, depressive symptoms, and self-efficacy from baseline were compared between caregivers and non-caregivers using paired t-tests and ANCOVA. Results Older informal caregivers had significantly lower session attendance rates than non-caregivers (67.7% vs 76.8%, P

Study objective: This study examined the association between frailty and incident cardiovascular disease (CVD) events, major adverse cardiovascular events (MACE), and CVD-related mortality. Design: Longitudinal cohort study. Setting: The ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial in Australia and the United States. Participants: 19,114 community-dwelling older adults (median age 74.0 years; 56.4 % females). Interventions: Pre-frailty and frailty were assessed using a modified Fried phenotype and a deficit accumulation Frailty Index (FI) at baseline. Main outcome measures: CVD was defined as a composite of CVD death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure; MACE included all except heart failure. Cox proportional hazards regression was used to analyze the association between frailty and CVD outcomes over a median follow-up of 4.7 years. Results: Baseline pre-frail and frail groups had a higher risk of incident CVD events (Hazard Ratio (HR): 1.31; 95 % Confidence Interval (CI): 1.14–1.50 for pre-frail and HR: 1.63; 95 % CI: 1.15–2.32 for frail) and MACE (pre-frail HR: 1.26; 95 % CI: 1.08–1.47 and frail HR: 1.51; 95 % CI: 1.00–2.29) than non-frail participants according to Fried phenotype after adjusting for traditional CVD risk factors. Effect sizes were similar or larger when frailty was assessed with FI; similar results for men and women. Conclusion: Frailty increases the likelihood of developing CVD, including MACE, in community-dwelling older men and women without prior CVD events. Screening for frailty using Fried or FI method could help identify community-dwelling older adults without prior CVD events who are more likely to develop CVD, including MACE, and may facilitate targeted preventive measures to reduce their risk.

ObjectiveBoth grip strength and gait speed can be used as markers of muscle function, however, no previous study has examined them in the same population with respect to risk of falls.MethodsIn this prospective cohort study, utilising data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and ASPREE-Fracture substudy, we analysed the association of grip strength and gait speed and serious falls in healthy older adults. Grip strength was measured using a handheld dynamometer and gait speed from 3-metre timed walks. Serious falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations with falls.ResultsOver an average of 4.0±1.3 years, amongst 16,445 participants, 1,533 had at least one serious fall. After adjustment for age, sex, physical activity, body mass index, Short Form 12 (state of health), chronic kidney disease, polypharmacy and aspirin, each standard deviation (SD) lower grip strength was associated with 27% (HR 1.27, 95% CI 1.17-1.38) higher risk of falls. The results remained the same for males and females. There was a dose-response relationship in the association between grip strength and falls risk. The higher risk of falls was observed in males in all body mass index (BMI) categories, but only in obese females. The association between gait speed and falls risk was weaker than the association between grip strength and falls risk.ConclusionsAll males and only obese females with low grip strength appear to be at the greatest risk of serious falls. These findings may assist in early identification of falls.

Abstract Background Older adults receive treatment for fall injuries in both inpatient and outpatient settings. The effect of persistent polypharmacy (i.e. using multiple medications over a long period) on fall injuries is understudied, particularly for outpatient injuries. We examined the association between persistent polypharmacy and treated fall injury risk from inpatient and outpatient settings in community-dwelling older adults. Methods The Health, Aging and Body Composition Study included 1764 community-dwelling adults (age 73.6 ± 2.9 years; 52% women; 38% black) with Medicare Fee-For-Service (FFS) claims at or within 6 months after 1998/99 clinic visit. Incident fall injuries (N = 545 in 4.6 ± 2.9 years) were defined as the initial claim with an ICD-9 fall E-code and non-fracture injury, or fracture code with/without a fall code from 1998/99 clinic visit to 12/31/08. Those without fall injury (N = 1219) were followed for 8.1 ± 2.6 years. Stepwise Cox models of fall injury risk with a time-varying variable for persistent polypharmacy (defined as ≥6 prescription medications at the two most recent consecutive clinic visits) were adjusted for demographics, lifestyle characteristics, chronic conditions, and functional ability. Sensitivity analyses explored if persistent polypharmacy both with and without fall risk increasing drugs (FRID) use were similarly associated with fall injury risk. Results Among 1764 participants, 636 (36%) had persistent polypharmacy over the follow-up period, and 1128 (64%) did not. Fall injury incidence was 38 per 1000 person-years. Persistent polypharmacy increased fall injury risk (hazard ratio [HR]: 1.31 [1.06, 1.63]) after adjusting for covariates. Persistent polypharmacy with FRID use was associated with a 48% increase in fall injury risk (95%CI: 1.10, 2.00) vs. those who had non-persistent polypharmacy without FRID use. Risks for persistent polypharmacy without FRID use (HR: 1.22 [0.93, 1.60]) and non-persistent polypharmacy with FRID use (HR: 1.08 [0.77, 1.51]) did not significantly increase compared to non-persistent polypharmacy without FRID use. Conclusions Persistent polypharmacy, particularly combined with FRID use, was associated with increased risk for treated fall injuries from inpatient and outpatient settings. Clinicians may need to consider medication management for FRID and other fall prevention strategies in community-dwelling older adults with persistent polypharmacy to reduce fall injury risk.

Abstract Cardiovacular disease (CVD) is the leading cause of death among older adults and is often accompanied by functional decline. It is unclear what is driving this co-occurrence, but it may be behavioral, environmental and/or genetic. We used a family-based study to estimate the phenotypic and shared genetic correlation between CVD risk factors and physical and cognitive functional measures. Participants (n = 1,881) were from the Long Life Family Study, which enrolled families based on their exceptional longevity (sample mean age = 69.4 years, 44% female). Cardiovascular disease risk factors included carotid vessel measures [intima-media thickness and inter-adventitial diameter], obesity [body mass index (BMI) and waist circumference], and hypertension [systolic and diastolic blood pressures]. Function was measured in the physical [gait speed, grip strength, chair stand] and cognitive [digital symbol substitution test, retained and working memory, semantic fluency, and trail making tests] domains. We used SOLAR to estimate the genetic, environmental, and phenotypic correlation between each pair adjusting for age, age2, sex, field center, smoking, height, and weight. There were significant phenotypic correlations (range |0.05–0.22|) between CVD risk factors and physical and cognitive function (all P

Multiple studies have observed a relationship of bone mineral density (BMD) measured by Dual energy X-ray absorptiometry (DXA) and mortality. However, areal BMD (aBMD) measured by DXA is an integrated measure of trabecular and cortical bone and does not measure the geometry of bone. Peripheral Quantitative Computed Tomography (pQCT) provides greater insights on bone structure, geometry and strength. To examine whether higher bone phenotypes and muscle density as measured by pQCT are associated with a lower all-cause mortality, we studied 245 men and 254 women (all age >60) recruited in the Mobility and Independent Living among Elders Study in rural south India. Cox proportional hazards models estimated hazard ratios (HR [95% Confidence Intervals]). After an average follow-up of 5.3 years, 73 men and 50 women died. Among men, trabecular volumetric bone mineral density (vBMD) of radius (HR per SD increase in parameter = 0.59 [0.43, 0.81]) and tibia (0.60[0.45, 0.81]), cortical vBMD of radius (0.61, [0.47, 0.79]) and tibia (0.62, [0.49, 0.79]), cortical thickness of radius (0.55, [0.42, 0.7]) and tibia (0.60, [0.47, 0.77]), polar strength strain index (SSIp) of tibia (0.73 [0.54, 0.98]), endosteal circumference of radius (1.63, [1.25, 2.12]) and tibia (1.54, [1.19, 1.98]) were associated with all-cause mortality. Muscle density (0.67, [0.51, 0.87]) was associated with lower mortality in men. Among women cortical vBMD of radius (0.64, [0.47, 0.87]) and tibia (0.60 [0.45, 0.79]), cortical thickness of radius (0.54, [0.37, 0.79]) and tibia (0.43, [0.30, 0.61]), SSIp of radius (0.70 [0.48,1.01]) and tibia (0.58 [0.37, 0.90]) and endosteal circumference of radius (1.33 [0.97, 1.82]) and tibia (1.83, [1.37, 2.45]) were associated with all-cause mortality. Among men, gait speed mediated the association of muscle density and mortality but there was no mediation for any bone parameters. Conclusion: pQCT bone measures and muscle density were independently associated with mortality among rural south Indian elders.

Background Aging is associated with central fat redistribution and skeletal muscle decline, yet the relationships of tissue compartments with heart failure (HF) remain incompletely characterized. We assessed the contribution of body composition to incident HF in elders. Methods and Results Participants from 2 older cohorts who completed dual‐energy X‐ray absorptiometry (DEXA) and, in one cohort, computed tomography were included. We evaluated associations with incident HF for DEXA principal components (PCs) and total lean, appendicular lean, total fat and trunk fat mass; and for computed tomography measures of abdominal visceral and subcutaneous fat, thigh muscle, intermuscular fat area and thigh muscle density. DEXA analysis included 3621, and computed tomography analysis 2332 participants. During median follow‐up of 11.8 years, 927 participants developed HF. DEXA principal components showed no relationship with HF. After adjustment for height, weight, and cardiovascular risk factors, total lean mass was near significantly associated with higher HF (hazard ratio [HR], 1.25 per SD [1.00–1.56]), whereas total fat mass and thigh muscle density were significantly related to lower HF (HR, 0.82 [0.68–0.99] and HR, 0.87 [0.78–0.97], respectively). Patterns were similar for HF subtypes. The relationships with HF for total lean and fat mass were attenuated after adjusting for intercurrent atrial fibrillation or excluding high natriuretic peptide levels. Conclusions Total lean mass was positively associated, while total fat mass and thigh muscle density were inversely associated, with incident HF. These findings highlight the limitations of DEXA for assessment of HF risk in elders and support the preeminence of computed tomography–measured skeletal muscle quality over mass as a determinant of HF incidence.

Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.

Background Intensive systolic blood pressure treatment (

Introduction As the population ages, there is interest in strategies to promote resiliency, especially for frail patients at risk of its complications. The physiological stress of surgery in high-risk individuals has been proposed both as an important cause of accelerated age-related decline in health and as a model testing the effectiveness of strategies to improve resiliency to age-related health decline. We describe a randomised, embedded, multifactorial, adaptative platform (REMAP) trial to investigate multiple perioperative interventions, the first of which is metformin and selected for its anti-inflammatory and anti-ageing properties beyond its traditional blood glucose control features.Methods and analysis Within a multihospital, single healthcare system, the Core Protocol for Strategies to Promote ResiliencY (SPRY) will be embedded within both the electronic health record (EHR) and the healthcare culture generating a continuously self-learning healthcare system. Embedding reduces the administrative burden of a traditional trial while accessing and rapidly analysing routine patient care EHR data. SPRY-Metformin is a placebo-controlled trial and is the first SPRY domain evaluating the effectiveness of three metformin dosages across three preoperative durations within a heterogeneous set of major surgical procedures. The primary outcome is 90-day hospital-free days. Bayesian posterior probabilities guide interim decision-making with predefined rules to determine stopping for futility or superior dosing selection. Using response adaptative randomisation, a maximum of 2500 patients allows 77%–92% power, detecting >15% primary outcome improvement. Secondary outcomes include mortality, readmission and postoperative complications. A subset of patients will be selected for substudies evaluating the microbiome, cognition, postoperative delirium and strength.Ethics and dissemination The Core Protocol of SPRY REMAP and associated SPRY-Metformin Domain-Specific Appendix have been ethically approved by the Institutional Review Board and are publicly registered. Results will be publicly available to healthcare providers, patients and trial participants following achieving predetermined platform conclusions.Trial registration number NCT03861767.

IntroductionSensory and motor nerve deficits are prevalent in older adults and are associated with loss of functional independence. We hypothesize that chronic kidney disease predisposes to worsening sensorimotor nerve function over time.Materials and methodsParticipants were from the Health, Aging and Body Composition Study (N = 1121) with longitudinal data between 2000-01 (initial visit) and 2007-08 (follow-up visit). Only participants with non-impaired nerve function at the initial visit were included. The predictor was presence of CKD (estimated GFR ≤ 60 ml/min/1.73m2) from the 1999-2000 visit. Peripheral nerve function outcomes at 7-year follow-up were 1) Motor: "new" impairments in motor parameters (nerve conduction velocity NCV < 40 m/s or peroneal compound motor action potential < 1 mv) at follow-up, and 2) Sensory: "new" impairment defined as insensitivity to standard 10-g monofilament or light 1.4-g monofilament at the great toe and "worsening" as a change from light to standard touch insensitivity over time. The association between CKD and "new" or "worsening" peripheral nerve impairment was studied using logistic regression.ResultsThe study population was 45.9% male, 34.3% Black and median age 75 y. CKD participants (15.6%) were older, more hypertensive, higher in BMI and had 2.37 (95% CI 1.30-4.34) fold higher adjusted odds of developing new motor nerve impairments in NCV. CKD was associated with a 2.02 (95% CI 1.01-4.03) fold higher odds of worsening monofilament insensitivity. CKD was not associated with development of new monofilament insensitivity.ConclusionsPre-existing CKD leads to new and worsening sensorimotor nerve impairments over a 7-year time period in community-dwelling older adults.

BackgroundConcentrations of fibroblast growth factor 23 (FGF-23), a hormone that regulates phosphorus and vitamin D metabolism, increase as kidney function declines. Excess fibroblast growth factor 23 may impact brain function through promotion of vascular disease or through direct effects on neuronal tissue.MethodsIn the Healthy Aging and Body Composition Study, a longitudinal observational cohort of well-functioning older adults, intact serum FGF-23 was assayed in 2,738 individuals. Cognitive function was assessed at baseline and longitudinally at years 3, 5, and 8 by administration of the Modified Mini Mental State Examination (3MSE), a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a test primarily of executive function. The associations between FGF-23 and baseline cognitive function and incident cognitive impairment were evaluated using logistic and Poisson regression respectively, and were adjusted for demographics, baseline estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, comorbidity, and other measures of mineral metabolism including soluble klotho.ResultsThe mean (SD) age was 74(3) years, with 51% female, and 39% black. The median (25th, 75th) FGF-23 concentration was 47 pg/mL (37, 60). Three hundred ninety-two individuals had prevalent cognitive impairment by the 3MSE and 461 by the DSST. There was no observed association between FGF-23 and baseline cognitive function for either cognitive test. There were 277 persons with incident cognitive impairment by 3MSE, and 333 persons with incident cognitive impairment by DSST. In fully adjusted models, each two-fold higher concentration of baseline FGF-23 was not associated with incident cognitive impairment by the 3MSE (IRR = 1.02[0.88, 1.19] fully adjusted model) or by the DSST (IRR = 0.98 [0.84, 1.15]. We saw no difference when analyses were stratified by eGFR greater than or less than 60 ml/min/1.73m2.ConclusionIntact FGF-23 was not associated with baseline cognitive function or incident cognitive impairment in this cohort well-functioning older adults.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Abstract 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

Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

Abstract Background Among older persons, disability is often precipitated by intervening illnesses and injuries leading to hospitalization. In the Lifestyle Interventions and Independence for Elders (LIFE) Study, a structured moderate-intensity physical activity program, compared with a health education program, was shown to significantly reduce the amount of time spent with major mobility disability (MMD) over the course of 3.5 years. We aimed to determine whether the benefit of the physical activity program in promoting independent mobility was diminished in the setting of intervening hospitalizations. Methods We analyzed data from a single-blinded, parallel group randomized trial (ClinicalTrials.gov: NCT01072500). In this trial, 1635 sedentary persons, aged 70–89 years, who had functional limitations but were able to walk 400 m, were randomized from eight US centers between February 2010 and December 2013: 818 to physical activity (800 received intervention) and 817 to health education (805 received intervention). Intervening hospitalizations and MMD, defined as the inability to walk 400 m, were assessed every 6 months for up to 3.5 years. Results For both the physical activity and health education groups, intervening hospitalizations were strongly associated with the initial onset of MMD and inversely associated with recovery from MMD, defined as a transition from initial MMD onset to no MMD. The benefit of the physical activity intervention did not differ significantly based on hospital exposure. For onset of MMD, the hazard ratios (HR) were 0.79 (95% confidence interval [CI] 0.58–1.1) and 0.77 (0.62–0.95) in the presence and absence of intervening hospitalizations, respectively (P-interaction, 0.903). For recovery of MMD, the magnitude of effect was modestly greater among participants who were hospitalized (HR 1.5, 95% CI 0.71–3.0) than in those who were not hospitalized (HR 1.2, 95% CI 0.88–1.7), but this difference did not achieve statistical significance (P-interaction, 0.670). Conclusions Intervening hospitalizations had strong deleterious effects on the onset of MMD and recovery from MMD, but did not diminish the beneficial effect of the LIFE physical activity intervention in promoting independent mobility. To achieve sustained benefits over time, structured physical activity programs should be designed to accommodate acute illnesses and injuries leading to hospitalizations given their high frequency in older persons with functional limitations. Trial registration ClinicalTrials.gov identifier NCT01072500 .

Myosteatosis is a complex condition, associated with aging and diverse pathological conditions (e.g., diabetes), that contributes to mobility disability. Improved characterization of myosteatosis is required to develop targeted interventions to maintain muscle health in aging. We first determined the associations between plasma metabolites and intermuscular fat (IMF) in a cross-sectional analysis of 313 older Black men from Health ABC Study. Using partial correlation analysis, 34/350 metabolites were associated with IMF, the majority of which were lipids and organic acids. Next, we used Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), as an indicator of metabolic health to delineate the anthropometric, functional, and metabolic heterogeneity of myosteatosis in a case-control matching analysis. We categorized participants based on their IMF and HOMA-IR levels into: Low-IMF with Low- versus High-HOMA, as well as High-IMF with Low- versus High-HOMA. Among participants with similar levels of IMF, those who were metabolically unhealthy, i.e., with High HOMA-IR, had higher fat and lean mass, muscle strength, and had hyperglycemia, hypertriglyceridemia, hyperinsulinemia, and higher levels of plasma metabolites belonging to diacylglycerols, triacylglycerols, fatty acid and aminoacyl-tRNA biosynthesis pathways versus those with Low HOMA-IR. In summary, HOMA-IR delineates the heterogeneity of myosteatosis by distinguishing metabolically healthy versus unhealthy individuals.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22613-2

Background Age‐related changes in blood pressure are associated with a variety of poor health outcomes. Genetic factors are proposed contributors to age‐related increases in blood pressure, but few genetic loci have been identified. We examined the role of mitochondrial genomic variation in blood pressure by sequencing the mitochondrial genome. Methods and Results Mitochondrial DNA (mtDNA) data from 1755 participants from the LIFE (Lifestyle Interventions and Independence for Elders) studies and 788 participants from the Health ABC (Health, Aging, and Body Composition) study were evaluated using replication analysis followed by meta‐analysis. Participants were aged ≥69 years, of diverse racial backgrounds, and assessed for systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure. After meta‐analysis across the LIFE and Health ABC studies, statistically significant associations of mtDNA variants with higher SBP (m.3197T>C, 16S rRNA; P=0.0005) and mean arterial pressure (m.15924A>G, t‐RNA‐thr; P=0.004) were identified in white participants. Among black participants, statistically significant associations with higher SBP (m.93A>G, HVII; m.16183A>C, HVI; both P=0.0001) and mean arterial pressure (m.16172T>C, HVI; m.16183A>C, HVI; m.16189T>C, HVI; m.12705C>T; all P's

BackgroundData are sparse regarding the value of physical activity (PA) surveillance among older adults—particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. Methods and ResultsCardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home‐based activity data were collected by hip‐worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84–0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65–0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow‐up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85–0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63–0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. ConclusionsObjective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.