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Background Slower gait speed may be driven by greater energy deficits and fatigability among older adults. We examined associations of walking energetics and perceived physical fatigability with gait speed among slower and faster walkers. Additionally, we used statistical mediation to examine the role of fatigability in the associations of walking energetics and gait speed using the Study of Muscle, Mobility and Aging (SOMMA). Methods Perceived physical fatigability was assessed using the Pittsburgh Fatigability Scale (PFS) Physical score (range 0–50, higher = greater). A 3-phase cardiopulmonary exercise treadmill test collected peak oxygen consumption (VO2peak, mL/kg/min), energetic cost of walking (ECW, mL/kg/m), and cost–capacity ratio (VO2/VO2peak*100, %). Slower (<1.01 m/s) versus faster (≥1.01 m/s) walkers were classified using median 4-m gait speed. Linear regressions and statistical mediation analyses were conducted. Results Slower walkers had lower VO2peak, higher ECW at preferred walking speed (PWS), and greater PFS Physical score compared to faster walkers (all p  < .05; N  = 849). One standard deviation (1- SD) higher VO2peak was associated with 0.1 m/s faster gait speed, while 1- SD higher ECW PWS, cost–capacity ratio at PWS and slow walking speed (SWS), and PFS Physical score were associated with 0.02–0.23 m/s slower gait speed. PFS Physical score was a significant statistical mediator in the associations between VO2peak (15.2%), SWS cost–capacity ratio (15.9%), and ECW PWS (10.7%) with gait speed and was stronger among slower walkers. Conclusions Slower walkers may be more influenced by perceptions of fatigue in addition to walking energetics. Our work highlights the importance of targeting both energetics and perceived fatigability to prevent mobility decline. [ABSTRACT FROM AUTHOR]

Background The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity. Methods The Study of Muscle, Mobility and Aging (SOMMA) assessed ex vivo muscle mitochondrial energetics in 764 older adults (mean age = 76.4, 56.5% women, and 85.9% non-Hispanic White) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95% CI]) for the likelihood of greater multimorbidity (4 levels: 0 conditions, N  = 332; 1 condition, N  = 299; 2 conditions, N  = 98; or 3+ conditions, N  = 35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions. Results Lower oxidative phosphorylation supported by fatty acids and/or complex I- and II-linked carbohydrates (eg, Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR = 1.32 [1.13, 1.54]) and separately with diabetes mellitus (OR = 1.62 [1.26, 2.09]), depressive symptoms (OR = 1.45 [1.04, 2.00]) and possibly chronic kidney disease (OR = 1.57 [0.98, 2.52]) but not significantly with other conditions (eg, cardiac arrhythmia, chronic obstructive pulmonary disease). Conclusions Lower muscle mitochondrial bioenergetic capacities were associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and are more strongly related to some conditions than others. [ABSTRACT FROM AUTHOR]

Background How magnetic resonance (MR) derived thigh muscle volume and deuterated creatine dilution derived muscle mass (D3Cr muscle mass) differentially relate to strength, fitness, and other functions in older adults—and whether associations vary by sex—is not known. Methods Men (N  = 345) and women (N  = 482) aged ≥70 years from the Study of Muscle, Mobility, and Aging completed leg extension strength (1-repetition max) and cardiopulmonary exercise testing to assess fitness (VO2peak). Correlations and adjusted regression models stratified by sex were used to assess the association between muscle size measures, study outcomes, and sex interactions. Results D3Cr muscle mass and MR thigh muscle volume were correlated (men: r  = 0.62, women: r  = 0.51, p  < .001). Each standard deviation (SD) decrement in D3Cr muscle mass was associated with lower 1-repetition max strength (−14 kg men, −4 kg women, p  < .001 for both; p -interaction = .003) and lower VO2peak (−79 mL/min men, −30 mL/min women, p  < .001 for both, p -interaction:.016). Each SD decrement in MR thigh muscle volume was also associated with lower strength (−32 kg men, −20 kg women, p  < .001 for both; p -interaction = .139) and lower VO2peak (−217 mL/min men, −111 mL/min women, p  < .001 for both, p -interaction = .010). There were associations, though less consistent, between muscle size or mass with physical performance and function; associations varied by sex. Conclusions Less muscle—measured by either D3Cr muscle mass or MR thigh muscle volume—was associated with lower strength and fitness. Varied associations by sex and assessment method suggest consideration be given to which measurement to use in future studies. [ABSTRACT FROM AUTHOR]

Background Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults. Methods We associated comprehensive muscle-related phenotypes including muscle mass normalized to body weight (D3-creatine dilution), muscle fat infiltration (magnetic resonance imaging), carbohydrate-supported muscle mitochondrial maximal oxidative phosphorylation (respirometry), and cardiorespiratory fitness (VO2 peak) with liver fat among older adults. Linear regression models adjusted for age, gender, technician (respirometry only), daily minutes of moderate-to-vigorous physical activity, and prediabetes/diabetes status tested main effects and interactions of each independent variable with waist circumference (high: women—≥88 cm, men—≥102 cm) and gender. Results Among older adults aged 75 (interquartile range: 73, 79 years; 59.8% women), muscle mass and liver fat were not associated overall (N  = 362) but were positively associated among participants with a high waist circumference (β: 25.2; 95% confidence intervals [95% CI]: 11.7, 40.4; p  = .0002; N  = 160). Muscle fat infiltration and liver fat were positively associated (β: 15.2; 95% CI: 6.8, 24.3; p  = .0003; N  = 378). Carbohydrate-supported maximum oxidative phosphorylation (before adjustment) and VO2 peak (after adjustment; β: −12.9; 95% CI: −20.3, −4.8; p  = .003; N  = 361) were inversely associated with liver fat; adjustment attenuated the estimate for maximum oxidative phosphorylation although the point estimate remained negative (β: −4.0; 95% CI: −11.6, 4.2; p  = .32; N  = 321). Conclusions Skeletal muscle-related characteristics are metabolically relevant factors linked to liver fat in older adults. Future research should confirm our results to determine whether trials targeting mechanisms common to liver and muscle fat accumulation are warranted. [ABSTRACT FROM AUTHOR]

The age-related decline in muscle mitochondrial energetics contributes to the loss of mobility in older adults. Women experience a higher prevalence of mobility impairment compared to men, but it is unknown whether sex-specific differences in muscle energetics underlie this disparity. In the Study of Muscle, Mobility and Aging (SOMMA), muscle energetics were characterized using in vivo phosphorus-31 magnetic resonance spectroscopy and high-resolution respirometry of vastus lateralis biopsies in 773 participants (56.4% women, age 70–94 years). A Short Physical Performance Battery (SPPB) score ≤8 was used to define lower-extremity mobility impairment. Muscle mitochondrial energetics were lower in women compared to men (eg, Maximal Complex I&II OXPHOS: Women = 55.06 ± 15.95; Men = 65.80 ± 19.74; p  < .001) and in individuals with mobility impairment compared to those without (eg, Maximal Complex I&II OXPHOS in women: SPPB ≥ 9 = 56.59 ± 16.22; SPPB ≤ 8 = 47.37 ± 11.85; p  < .001). Muscle energetics were negatively associated with age only in men (eg, Maximal ETS capacity: R  = −0.15, p  = .02; age/sex interaction, p  = .04), resulting in muscle energetics measures that were significantly lower in women than men in the 70–79 age group but not the 80+ age group. Similarly, the odds of mobility impairment were greater in women than men only in the 70–79 age group (70–79 age group, odds ratio [OR]age-adjusted = 1.78, 95% confidence interval [CI] = 1.03, 3.08, p  = .038; 80+ age group, ORage-adjusted = 1.05, 95% CI = 0.52, 2.15, p  = .89). Accounting for muscle energetics attenuated up to 75% of the greater odds of mobility impairment in women. Women had lower muscle mitochondrial energetics compared to men, which largely explain their greater odds of lower-extremity mobility impairment. [ABSTRACT FROM AUTHOR]

Background Falls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated. Methods In this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70–94 were surveyed for number of falls (total), recurrent falls (2+), and fall-related injuries over the past 12 months at baseline and again after 1 year. Skeletal muscle energetics were assessed at baseline in vivo using 31P Magnetic Resonance Spectroscopy for the maximal rate of adenosine triphosphate recovery (ATPmax) after an acute bout of exercise, and ex vivo by High-Resolution Respirometry for the maximal rate of complex I and II supported oxygen consumption (MaxOXPHOS) in permeabilized muscle fibers from the vastus lateralis. Results At least 1 fall was reported in 28.7% of SOMMA participants in the first year of the study, with 12% of older adults reporting recurrent falls (2+). Individuals who experienced recurrent falls had a slower 400-m walk gait speed (1.0 ± 0.2 vs 1.1 ± 0.2, p <.001), reported fewer alcoholic drinks per week in the past year (2.4 ± 4.3 vs 2.8 ± 4.4, p =.054), and took a significantly greater number of medication in the 30 days before their baseline visit (5.6 ± 4.4 vs 4.2 ± 3.4, p <.05). A history of falls was reported in 63% of individuals who experienced recurrent falls in the first year of the study compared to 22.8% who experienced 1 or fewer falls. MaxOXPHOS was significantly lower in those who reported recurrent falls (p =.008) compared to those with 1 or fewer falls, but there was no significant difference in ATPmax (p =.369). Neither muscle energetics measure was significantly associated with total number of falls or injurious falls, but recurrent falls were significantly higher with lower MaxOXPHOS (risk ratio = 1.33, 95% confidence interval = 1.02–1.73, p =.033). However, covariates accounted for the increased risk. Conclusions Mitochondrial energetics were largely unrelated to fall risk in older adults when accounting for variables, suggesting that the complex etiology of falls may not be related to a single "hallmark of aging" biological pathway. [ABSTRACT FROM AUTHOR]

Background Frailty can occur in older adults without disability or multimorbidity. Current methods focus on the most frail, but poorly discriminate among those "not frail." Methods The Study of Muscle, Mobility, and Aging (SOMMA) included 879 adults aged 70 years and older without mobility disability. We operationalized frailty domains using: peak oxygen consumption (endurance), digit symbol substitution test (speed), leg power (strength), perceived fatigability, D3 creatine dilution (sarcopenia), and accelerometry (sedentary behavior) to construct a frailty score of 0–12 summing tertiles (0–2) of each component. We used linear or logistic regression with and without adjustment for confounders to examine associations with age, reported, and performance function. Results The SOMMA frailty score distribution was broad and strongly associated with age (r  = 0.33, p  < .0001). Each point was associated with a 30%–50% higher odds of having reported difficulty with activities of daily living or mobility. After grouping the total score (0–3, 4–7, and 8–12) those in the highest group were 9–31 times more likely to have functional limitation, and at least 8 times more likely to have poorer function after full adjustment. Higher scores identified those less likely to report ease of walking or higher physical activity. Peak oxygen consumption, leg power, fatigability, and digit symbol score contributed most to these associations. Conclusions The SOMMA frailty score characterizes frailty as a continuum from frail to vigorous with assessments that are amenable to change. Associations with age and function suggest utility for distinguishing a wide range of vigor and vulnerability in relatively well-functioning older adults. [ABSTRACT FROM AUTHOR]

Background The Pittsburgh Performance Fatigability Index (PPFI) quantifies the percent decline in cadence using accelerometry during standardized walking tasks. Although PPFI has shown strong correlations with physical performance, the developmental sample was relatively homogenous and small, necessitating further validation. Methods Participants from the Study of Muscle, Mobility and Aging (N  = 805, age = 76.4 ± 5.0 years, 58% women, 85% White) wore an ActiGraph GT9X on the nondominant wrist during usual-paced 400 m walk. Tri-axial accelerations were analyzed to compute PPFI (higher score = greater fatigability). To evaluate construct and discriminant validity, Spearman correlations (r s) between PPFI and gait speed, Short Physical Performance Battery (SPPB), chair stand speed, leg peak power, VO2peak, perceived fatigability, and mood were examined. Sex-specific PPFI cut-points that optimally discriminated gait speed using classification and regression tree were then generated. Their discriminate power in relation to aforementioned physical performance were further evaluated. Results Median PPFI score was 1.4% (25th–75th percentile range: 0%–21.7%), higher among women than men (p  < .001). PPFI score was moderate-to-strongly correlated with gait speed (r s = −0.75), SPPB score (r s = −0.38), chair stand speed (r s = −0.36), leg peak power (r s = −0.34) and VO2peak (r s = −0.40), and less strongly with perceived fatigability (r s = 0.28–0.29), all p  < .001. PPFI score was not correlated with mood (| r s| < 0.08). Sex-specific PPFI cut-points (no performance fatigability: PPFI = 0%; mild performance fatigability: 0% < PPFI < 3.5% [women], 0% < PPFI < 5.4% [men]; moderate-to-severe performance fatigability: PPFI ≥ 3.5% [women], PPFI ≥ 5.4% [men]) discriminated physical performance (all p  < .001), adjusted for demographics and smoking status. Conclusion Our work underscores the utility of PPFI as a valid measure to quantify performance fatigability in future longitudinal epidemiologic studies and clinical/pharmaceutical trials. [ABSTRACT FROM AUTHOR]

Background Myostatin, a cytokine produced by skeletal muscle, may influence Alzheimer's disease (AD) pathogenesis, but sparse evidence exists in humans. We assessed the association between circulating levels of myostatin at Year 1 and plasma levels of β-amyloid 42/40 at Year 2, a marker of AD pathology, in a biracial cohort of older adults. Methods We studied 403 community-dwelling older adults enrolled in the Health, Aging and Body Composition Study from Memphis, Tennessee, and Pittsburgh, PA. Mean age was 73.8 ± 3 years; 54% were female; and 52% were Black. Serum myostatin levels were measured at Year 1, plasma β-amyloid 42/40 levels in Year 2 (higher ratio indicating lower amyloid load). Multivariable linear regression analyses tested the association of serum myostatin with plasma levels of β-amyloid 42/40 adjusted for computed-tomography-derived thigh muscle cross-sectional area, demographics, APOe4 allele, and risk factors for dementia. We tested for 2-way.interactions between myostatin and race or sex; results were stratified by race and sex. Results In multivariable models, myostatin was positively associated with plasma levels of β-amyloid 42/40 (standardized regression coefficient: 0.145, p =.004). Results were significant for white men and women (0.279, p =.009, and 0.221, p =.035, respectively) but not for Black men or women; interactions by race and gender were not statistically significant. Conclusions Higher serum myostatin was associated with lower amyloid burden, independently of APOe4 alleles, muscle area and other established risk factors for dementia. The role of myostatin in AD pathogenesis and the influence of race should be further investigated. [ABSTRACT FROM AUTHOR]

Background The Study of Muscle, Mobility and Aging (SOMMA) aims to understand the biological basis of many facets of human aging, with a focus on mobility decline, by creating a unique platform of data, tissues, and images. Methods The multidisciplinary SOMMA team includes 2 clinical centers (University of Pittsburgh and Wake Forest University), a biorepository (Translational Research Institute at Advent Health), and the San Francisco Coordinating Center (California Pacific Medical Center Research Institute). Enrollees were age ≥70 years, able to walk ≥0.6 m/s (4 m); able to complete 400 m walk, free of life-threatening disease, and had no contraindications to magnetic resonance or tissue collection. Participants are followed with 6-month phone contacts and annual in-person exams. At baseline, SOMMA collected biospecimens (muscle and adipose tissue, blood, urine, fecal samples); a variety of questionnaires; physical and cognitive assessments; whole-body imaging (magnetic resonance and computed tomography); accelerometry; and cardiopulmonary exercise testing. Primary outcomes include change in walking speed, change in fitness, and objective mobility disability (able to walk 400 m in 15 minutes and change in 400 m speed). Incident events, including hospitalizations, cancer diagnoses, fractures, and mortality are collected and centrally adjudicated by study physicians. Results SOMMA exceeded its goals by enrolling 879 participants, despite being slowed by the COVID-19 pandemic: 59.2% women; mean age 76.3 ± 5.0 years (range 70–94); mean walking speed 1.04 ± 0.20 m/s; 15.8% identify as other than Non-Hispanic White. Over 97% had data for key measurements. Conclusions SOMMA will provide the foundation for discoveries in the biology of human aging and mobility. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial energetics are an important property of aging muscle, as generation of energy is pivotal to the execution of muscle contraction. However, its association with functional outcomes, including leg power and cardiorespiratory fitness is largely understudied.Methods: In the Study of Muscle, Mobility, and Aging (SOMMA), we collected vastus lateralis biopsies from older adults (n=879,70-94 years,59.2% women). Maximal state 3 respiration (Max OXPHOS) was assessed in permeabilized fiber bundles by high-resolution respirometry. Capacity for maximal adenosine triphosphate production (ATPmax) was measured in vivo by 31P magnetic resonance spectroscopy. Leg extension power was measured with a Keiser press system, and VO2 peak was determined using a standardized cardiopulmonary exercise test. Gender-stratified multivariate linear regression models were adjusted for age, race, technician/site, adiposity, and physical activity with beta-coefficients expressed per 1 SD increment in the independent variable.Results: Max OXPHOS was associated with leg power for both women (β=0.12Watts/kg,p<0.001) and men (β=0.11Watts/kg,p<0.050). ATPmax was associated with leg power for men (β=0.09Watts/kg p<0.05) but was not significant for women (β=0.03Watts/kg,p=0.11). Max OXPHOS and ATPmax were associated with VO2 peak in women and men (Max OXPHOS, βwomen=1.03mL/kg/min, βmen=1.32 mL/kg/min; ATPmax βwomen=0.87mL/kg/min, βmen=1.50mL/kg/min;all p<0.001).Conclusions: Higher muscle mitochondrial energetics measures were associated with both better cardiorespiratory fitness and greater leg power in older adults. Muscle mitochondrial energetics explained a greater degree of variance in VO2 peak compared to leg power. [ABSTRACT FROM AUTHOR]

Background Cardiorespiratory fitness and perceived fatigability are interrelated components of physical capacity that may jointly influence movement within one's living environment (life-space mobility). We examined whether fitness and fatigability were associated with life-space mobility in community-dwelling older adults, and whether the association of fitness with life-space varied by the level of perceived fatigability. Methods Participants were from the Study of Muscle, Mobility and Aging (SOMMA) baseline cohort (N = 775, mean age 76.1 years). Life Space Assessment scores incorporated level, frequency, and assistance used (personal, devices) for life-space mobility. Fitness was measured as VO2peak from symptom-limited treadmill testing. Fatigability cut-points included: (i) Borg Rating of Perceived Exertion (RPE) ≥ 10 after a fixed-speed (1.5 mph) treadmill test, (ii) the Pittsburgh Fatigability Scale (PFS) Physical ≥ 15, and (iii) PFS Mental ≥ 13. The total count of cut-points was used as a composite fatigability measure (range: 0–3). Linear regressions were adjusted for demographic, lifestyle, and health confounders. Results Better fitness was associated with greater life-space, but the association plateaued at higher fitness levels (VO2peak > 18). Life-space was significantly lower for individuals meeting ≥2 fatigability criteria (vs none), attributable mainly to more severe physical, but not mental, fatigability. In moderation analyses, the fitness–life-space association was significant only for those with RPE ≥ 10 but did not differ by PFS. Conclusion Fitness below a critically low threshold was associated with limited life-space mobility, suggesting that certain older individuals may need to operate close to their maximum aerobic capacity to traverse daily environments; these associations were driven by those with more severe physical fatigability. [ABSTRACT FROM AUTHOR]

Background: Aging-related disease risk is exacerbated by obesity and physical inactivity. It is unclear how weight loss and increased activity improve risk in older adults. We aimed to determine the effects of diet-induced weight loss with and without exercise on insulin sensitivity, VO2peak, body composition, and physical function in older obese adults.Methods: Physically inactive older (68.6 ± 4.5 years) obese (body mass index 37.4 ± 4.9 kg/m2) adults were randomized to health education control (HEC; n = 25); diet-induced weight loss (WL; n = 31); or weight loss and exercise (WLEX; n = 28) for 6 months. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, body composition by dual-energy X-ray absorptiometry and MRI, strength by isokinetic dynamometry, and VO2peak by graded exercise test.Results: WLEX improved (p < .05) peripheral insulin sensitivity (+75 ± 103%) versus HEC (+12 ± 67%); WL (+36 ± 47%) versus HEC did not reach statistical significance. WLEX increased VO2peak (+7 ± 12%) versus WL (-2 ± 24%) and prevented reductions in strength and lean mass induced by WL (p < .05). WLEX decreased abdominal adipose tissue (-16 ± 9%) versus HEC (-3 ± 8%) and intermuscular adipose tissue (-15 ± 13%) versus both HEC (+9 ± 15%) and WL (+2 ± 11%; p < .01).Conclusions: Exercise with weight loss improved insulin sensitivity and VO2peak, decreased ectopic fat, and preserved lean mass and strength. Weight loss alone decreased lean mass and strength. Older adults intending to lose weight should perform regular exercise to promote cardiometabolic and functional benefits, which may not occur with calorie restriction-induced weight loss alone. [ABSTRACT FROM AUTHOR]

Background: Age-related deposition of fat in skeletal muscle is associated with functional limitations. Skeletal muscle fat may be present in people with preserved muscle mass or accompanied by muscle wasting. However, it is not clear if the association between muscle fat deposition and physical performance is moderated by muscle mass.Objective: To determine whether the association between midthigh intermuscular fat and physical performance is moderated by muscle area.Methods: We performed a cross-sectional analysis of the Health, Aging, and, Body Composition (ABC) study data collected in 2002-2003 (n = 1897, women: 52.2%). Midthigh muscle cross-sectional area (by computed tomography) and physical performance measures were compared across quartiles of intermuscular fat absolute area. Moderation analysis was performed to determine the conditional effect of intermuscular fat on physical performance as a function of muscle area. Conditional effects were evaluated at three levels of muscle area (mean and ± 1 standard deviation [SD]; 213.2 ± 53.2 cm2).Results: Simple slope analysis showed that the negative association between intermuscular fat area (cm2) and leg strength (N·m) was of greater magnitude (beta coefficient [b], 95% confidence interval [CI] = -0.288 [-0.427, -0.148]) in participants with greater muscle area (ie, 1 SD above the mean) compared to those with lower muscle area (ie, at mean [b = -0.12 {-0.248, 0.008}] or 1 SD below the mean [b = 0.048 {-0.122, 0.217}]). Similarly, the negative association of intermuscular fat with 400-m walk speed (m/s) and chair stand (seconds) was greater in those with higher muscle areas (p < .001) compared to those with lower muscle areas.Conclusions: The association between higher intermuscular fat area and impaired physical function in aging is moderated by muscle area. [ABSTRACT FROM AUTHOR]

Background: Older adults exposed to periods of inactivity during hospitalization, illness, or injury lose muscle mass and strength. This, in turn, predisposes poor recovery of physical function upon reambulation and represents a significant health risk for older adults. Bed rest (BR) results in altered skeletal muscle fuel metabolism and loss of oxidative capacity that have recently been linked to the muscle atrophy program. Our primary objective was to explore the effects of BR on mitochondrial energetics in muscle from older adults. A secondary objective was to examine the effect of β-hydroxy-β-methylbuturate (HMB) supplementation on mitochondrial energetics.Methods: We studied 20 older adults before and after a 10-day BR intervention, who consumed a complete oral nutritional supplement (ONS) with HMB (3.0 g/d HMB, n = 11) or without HMB (CON, n = 9). Percutaneous biopsies of the vastus lateralis were obtained to determine mitochondrial respiration and H2O2 emission in permeabilized muscle fibers along with markers of content. RNA sequencing and lipidomics analyses were also conducted.Results: We found a significant up-regulation of collagen synthesis and down-regulation of ribosome, oxidative metabolism and mitochondrial gene transcripts following BR in the CON group. Alterations to these gene transcripts were significantly blunted in the HMB group. Mitochondrial respiration and markers of content were both reduced and H2O2 emission was elevated in both groups following BR.Conclusions: In summary, 10 days of BR in older adults causes a significant deterioration in mitochondrial energetics, while transcriptomic profiling revealed that some of these negative effects may be attenuated by an ONS containing HMB. [ABSTRACT FROM AUTHOR]

The progression of age-related sarcopenia can be accelerated by impaired recovery of muscle mass following periods of disuse due to illness or immobilization. However, the mechanisms underlying poor recovery of aged muscle following disuse remain to be delineated. Recent evidence suggests that mitochondrial energetics play an important role in regulation of muscle mass. Here, we report that 22- to 24-month-old mice with low muscle mass and low glucose clearance rate also display poor early recovery of muscle mass following 10 days of hind limb unloading. We used unbiased and targeted approaches to identify changes in energy metabolism gene expression, metabolite pools and mitochondrial phenotype, and show for the first time that persistent mitochondrial dysfunction, dysregulated fatty acid β-oxidation, and elevated H2O2 emission occur concomitantly with poor early recovery of muscle mass following a period of disuse in old mice. Importantly, this is linked to more severe whole-body insulin resistance, as determined by insulin tolerance test. The findings suggest that muscle fuel metabolism and mitochondrial energetics could be a focus for mining therapeutic targets to improve recovery of muscle mass following periods of disuse in older animals. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals.Methods: Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10). Mitochondrial volume density, mitochondria membrane content (cardiolipin), and activities of electron transport chain (rotenone-sensitive NADH-oxidase), tricarboxylic acid (TCA) cycle (citrate synthase) and β-oxidation pathway (β-hydroxyacyl CoA dehydrogenase; β-HAD) were measured in percutaneous biopsies of the vastus lateralis before and after the interventions.Results: Rd improved similarly (18.2% ± 9.0%, p < .04) with both weight loss and exercise. Moderate exercise significantly increased mitochondrial volume density (14.5% ± 2.0%, p < .05), cardiolipin content (22.5% ± 13.4%, p < .05), rotenone-sensitive NADH-oxidase (65.7% ± 13.2%, p = .02) and β-HAD (30.7% ± 6.8%, p ≤ .03) activity, but not citrate synthase activity (10.1% ± 4.0%). In contrast, calorie restriction-induced weight loss did not affect mitochondrial content, NADH-oxidase or β-HAD, yet increased citrate synthase activity (44.1% ± 21.1%, p ≤ .04). Exercise (increase) or weight loss (decrease) induced a remodeling of cardiolipin with a small (2%-3%), but significant change in the relative content of tetralinoleoyl cardiolipin.Conclusion: Exercise increases both mitochondria content and mitochondrial electron transport chain and fatty acid oxidation enzyme activities within skeletal muscle, while calorie restriction-induced weight loss did not, despite similar improvements in insulin sensitivity in overweight older adults. [ABSTRACT FROM AUTHOR]

To identify biomarkers of body mass index, body fat, trunk fat, and appendicular lean mass, nontargeted metabolomics was performed in plasma from 319 black men in the Health, Aging and Body Composition study (median age 72 years, median body mass index 26.8 kg/m2). Body mass index was calculated from measured height and weight; percent fat, percent trunk fat, and appendicular lean mass were measured with dual-energy x-ray absorptiometry. Pearson partial correlations between body composition measures and metabolites were adjusted for age, study site, and smoking. Out of 350 metabolites, body mass index, percent fat, percent trunk fat, and appendicular lean mass were significantly correlated with 92, 48, 96, and 43 metabolites at p less than .0014. Metabolites most strongly correlated with body composition included carnitine, a marker of fatty acid oxidation (positively correlated), triacylglycerols (positively correlated), and amino acids including branched-chain amino acids (positively correlated except for acetylglycine and serine). Gaussian Graphical Models of metabolites found that 25 lipid metabolites clustered into a single network. Groups of five amino acids, three plasmalogens, and two carnitines were also observed. Findings confirm prior reports of associations between amino acids, lean mass, and fat mass in addition to associations not previously reported. Future studies should consider whether these metabolites are relevant for metabolic disease processes. [ABSTRACT FROM AUTHOR]

Background: Age-related losses of lean mass and shifts to central adiposity are related to functional decline and may predict mortality and/or explain part of the risk of weight loss. To determine how mortality risk is related to shifts in body composition, changes should be considered in the context of overall weight change.Methods: Five-year changes in body composition were assessed with computed tomography (cm2) and dual x-ray absorptiometry (kg) in 869 men and 934 women initially aged 70-79 years. All-cause mortality was monitored for up to 12 years (2002-2003 to September 30, 2014), and risk was assessed using sex-specific Cox models.Results: Both men and women lost weight, visceral fat area, thigh muscle area, lean mass, and fat mass (all p < .01) but gained intermuscular thigh fat area (p < .01). There were 995 deaths. After adjustment for total weight change, demographics, and chronic disease, losing thigh muscle area was associated with higher mortality in both men (1.21, 1.08-1.35) and women (1.18, 1.01-1.37, per 9.0cm2) and was especially strong in normal weight (body mass index < 25kg/m2) individuals and those losing weight. Losing intermuscular thigh fat was protective against mortality only in normal weight (0.66, 0.51-0.86) and weight stable men (0.79, 0.66-0.95, per 3.2cm2). Changes in visceral fat area were not associated with mortality.Conclusions: Older adults with greater loss of thigh muscle than expected for overall weight change had a higher mortality risk compared to those with relative thigh muscle preservation, suggesting that conservation of muscle mass is important for survival in old age. [ABSTRACT FROM AUTHOR]

Background: Considerable debate continues to surround the concept of mitochondrial dysfunction in aging muscle. We tested the overall hypothesis that age per se does not influence mitochondrial function and markers of mitochondria quality control, that is, expression of fusion, fission, and autophagy proteins. We also investigated the influence of cardiorespiratory fitness (VO2max) and adiposity (body mass index) on these associations.Methods: Percutaneous biopsies of the vastus lateralis were obtained from sedentary young (n = 14, 24±3 years), middle-aged (n = 24, 41±9 years) and older adults (n = 20, 78±5 years). A physically active group of young adults (n = 10, 27±5 years) was studied as a control. Mitochondrial respiration was determined in saponin permeabilized fiber bundles. Fusion, fission and autophagy protein expression was determined by Western blot. Cardiorespiratory fitness was determined by a graded exercise test.Results: Mitochondrial respiratory capacity and expression of fusion (OPA1 and MFN2) and fission (FIS1) proteins were not different among sedentary groups despite a wide age range (21 to 88 years). Mitochondrial respiratory capacity and fusion and fission proteins were, however, negatively associated with body mass index, and mitochondrial respiratory capacity was positively associated with cardiorespiratory fitness. The young active group had higher respiration, complex I and II respiratory control ratios, and expression of fusion and fission proteins. Finally, the expression of fusion, fission, and autophagy proteins were linked with mitochondrial respiration.Conclusions: Mitochondrial respiration and markers of mitochondrial dynamics (fusion and fission) are not associated with chronological age per se, but rather are more strongly associated with body mass index and cardiorespiratory fitness. [ABSTRACT FROM AUTHOR]

Background: Mobility limitation is highly prevalent among older adults and is central to the loss of functional independence. Dynamic isokinetic muscle fatigue testing may reveal increased vulnerability to disability and mortality beyond strength testing.Methods: We studied community-dwelling older adults enrolled in the Health Aging and Body Composition study (age range: 71-82) free of mobility disability and who underwent isokinetic muscle fatigue testing in 1999-2000 (n = 1,963). Isokinetic quadriceps work and fatigue index was determined over 30 repetitions and compared with isometric quadriceps maximum torque. Work was normalized to leg lean mass accounting for gender-specific differences (specific work). The primary outcome was incident persistent severe lower extremity limitation (PSLL), defined as two consecutive reports of either having a lot of difficulty or being unable to walk 1/4 mile or climb 10 steps without resting. The secondary outcome was all-cause mortality.Results: There were 608 (31%) occurrences of incident PSLL and 488 (25%) deaths during median follow-up of 9.3 years. After adjustment, lower isokinetic work was associated with significantly greater risks of PSLL and mortality across the full measured range. Hazard ratios per standard deviation lower specific isokinetic work were 1.22 (95% CI 1.12, 1.33) for PSLL and 1.21 (95% CI 1.13, 1.30) for mortality, respectively. Lower isometric strength was associated with PSLL, but not mortality. Fatigue index was not associated with PSLL or mortality.Conclusions: Muscle endurance, estimated by isokinetic work, is an indicator of muscle health associated with mobility limitation and mortality providing important insight beyond strength testing. [ABSTRACT FROM AUTHOR]

Background: Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults.Methods: The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m(2) and usual gait-speed of 1.2 ± 0.2 m/s. Fatigability was defined using rating of perceived exertion (6-20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using (31)P magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax (mM ATP/s) and oxidative capacity of the quadriceps (ATPmax·Quadriceps volume) were calculated. Peak aerobic capacity (VO2peak) was measured using a modified Balke protocol.Results: ATPmax·Quadriceps volume was associated with VO2peak and was 162.61mM ATP·mL/s lower (p = .03) in those with high (rating of perceived exertion ≥10) versus low (rating of perceived exertion ≤9) fatigability. Participants with high fatigability required a significantly higher proportion of VO2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11-1.01, p = .05).Conclusions: Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults. [ABSTRACT FROM AUTHOR]

Background: Hip fracture is an important problem for older adults with significant functional consequences. After hip fracture, reduced muscle loading can result in muscle atrophy.Methods: We compared thigh muscle characteristics in the fractured leg to those in the nonfractured leg in participants from the Baltimore Hip Studies 7th cohort using computed tomography scan imaging.Results: At 2 months postfracture, a single 10mm axial computed tomography scan was obtained at the midthigh level in 43 participants (23 men, 20 women) with a mean age of 79.9 years (range: 65-96 years), and thigh muscle cross-sectional area, cross-sectional area of intermuscular adipose tissue, and mean radiologic attenuation were measured. Total thigh muscle cross-sectional area was less on the side of the fracture by 9.46cm(2) (95% CI: 5.97cm(2), 12.95cm(2)) while the cross-sectional area of intermuscular adipose tissue was greater by 2.97cm(2) (95% CI: 1.94cm(2), 4.01cm(2)) on the fractured side. Mean muscle attenuation was lower on the side of the fracture by 3.66 Hounsfield Units (95% CI: 2.98 Hounsfield Units, 4.34 Hounsfield Units).Conclusions: The observed asymmetry is consistent with the effect of disuse and inflammation in the affected limb along with training effects in the unaffected limb due to the favoring of this leg with ambulation during the postfracture period. [ABSTRACT FROM AUTHOR]

Background. Poor peripheral nerve function is common in older adults and may be a risk factor for strength decline, although this has not been assessed longitudinally. Methods. We assessed whether sensorimotor peripheral nerve function predicts strength longitudinally in 1,830 participants (age = 76.3 ± 2.8, body mass index = 27.2 ± 4.6kg/m², strength = 96.3 ± 34.7 Nm, 51.0% female, 34.8% black) from the Health ABC study. Isokinetic quadriceps strength was measured semiannually over 6 years. Peroneal motor nerve conduction amplitude and velocity were recorded. Sensory nerve function was assessed with 10-g and 1.4-g mono-filaments and average vibration detection threshold at the toe. Lower-extremity neuropathy symptoms were self-reported. Results. Worse vibration detection threshold predicted 2.4% lower strength in men and worse motor amplitude and two symptoms predicted 2.5% and 8.1% lower strength, respectively, in women. Initial 10-g monofilament insensitivity predicted 14.2% lower strength and faster strength decline in women and 6.6% lower strength in men (allp < .05). Conclusion. Poor nerve function predicted lower strength and faster strength decline. Future work should examine interventions aimed at preventing declines in strength in older adults with impaired nerve function. [ABSTRACT FROM AUTHOR]

Background: Diagnostic criteria for sarcopenia from appendicular lean mass (ALM), strength, and performance have been proposed, but little is known regarding the progression of sarcopenia. We examined the time course of sarcopenia and determinants of transitioning toward and away from sarcopenia.Methods: ALM, gait speed, and grip strength were assessed seven times over 9 years in 2,928 initially well-functioning adults aged 70-79. Low ALM was defined as less than 7.95 kg/m(2) (men) or less than 6.24 kg/m(2) (women), low performance as gait speed less than 1.0 m/s, low strength as grip strength less than 30 kg (men) or less than 20 kg (women). Presarcopenia was defined as low ALM and sarcopenia as low ALM with low performance or low strength. Hidden Markov modeling was used to characterize states of ALM, strength, and performance and model transitions leading to sarcopenia and death. Determinants of transitioning toward and away from sarcopenia were examined with logistic regression.Results: Initially, 54% of participants had normal ALM, strength, and performance; 21% had presarcopenia; 5% had sarcopenia; and 20% had intermediate characteristics. Of participants with normal ALM, strength, and performance, 1% transitioned to presarcopenia and none transitioned to sarcopenia. The greatest transition to sarcopenia (7%) was in presarcopenic individuals. Low-functioning and sarcopenia states were more likely to lead to death (12% and 13%). Higher body mass index (p < .001) and pain (p = .05) predicted transition toward sarcopenia, whereas moderate activity predicted transition from presarcopenia to more normal states (p = .02).Conclusions: Pain, physical activity, and body mass index, potentially modifiable factors, are determinants of transitions. Promotion of health approaching old age is important as few individuals transition away from their initial state. [ABSTRACT FROM AUTHOR]

Background. Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics. Methods. VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4–13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics. Results. Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.36–2.80; Health ABC) and 1.88 (1.31–2.69; AGES-Reykjavik) and for SAT density, 1.76 (1.35–2.28; Health ABC) and 1.56 (1.15–2.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.12–2.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.21–2.07), and AGES-Reykjavik, 1.43 (1.07–1.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs. Conclusion. VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related. [ABSTRACT FROM PUBLISHER]

Background. Older women have higher percent body fat, poorer physical function, lower strength, and higher rates of nonfatal chronic conditions than men. We sought to determine whether these differences explained physical performance differences between men and women. Methods. Physical performance was assessed in the Health, Aging and Body Composition study in 2,863 men and women aged 70–79 with a composite 0–4 point score consisting of chair stands, standing balance including one-leg stand, and 6-m usual and narrow walk tests. Total body composition was measured by dual x-ray absorptiometry, thigh composition by computed tomography, and knee extensor strength by isokinetic dynamometer. Analysis of covariance estimated least square mean performance scores for men and women. Results. Men had higher performance scores than women (least square means: 2.33±0.02 vs 2.03±0.02, p < .0001), adjusted for race, study site, age, and height. Body composition measures (total body fat and thigh muscle area, muscle density, subcutaneous fat, and intermuscular fat) accounted for differences between men and women (least square means: 2.15±0.02 vs 2.17±0.02, p = .53). Higher strength in men partly explained the sex difference (least square means: 2.28±0.02 vs 2.12±0.02, p < .0001). Strength attenuated the association of thigh muscle mass with performance. Chronic health conditions did not explain the sex difference. Conclusions. In a well-functioning cohort, poorer physical function in women compared with men can be explained predominantly by their higher fat mass, but also by other body composition differences. The higher proportion of body fat in women may put them at significant biomechanical disadvantage for greater disability in old age. [ABSTRACT FROM PUBLISHER]

Background. Lower ambulatory performance with aging may be related to a reduced oxidative capacity within skeletal muscle. This study examined the associations between skeletal muscle mitochondrial capacity and efficiency with walking performance in a group of older adults. Methods. Thirty-seven older adults (mean age 78 years; 21 men and 16 women) completed an aerobic capacity (VO2 peak) test and measurement of preferred walking speed over 400 m. Maximal coupled (State 3; St3) mitochondrial respiration was determined by high-resolution respirometry in saponin-permeabilized myofibers obtained from percutanous biopsies of vastus lateralis (n = 22). Maximal phosphorylation capacity (ATPmax) of vastus lateralis was determined in vivo by 31P magnetic resonance spectroscopy (n = 30). Quadriceps contractile volume was determined by magnetic resonance imaging. Mitochondrial efficiency (max ATP production/max O2 consumption) was characterized using ATPmax per St3 respiration (ATPmax/St3). Results. In vitro St3 respiration was significantly correlated with in vivo ATPmax (r2 = .47, p = .004). Total oxidative capacity of the quadriceps (St3*quadriceps contractile volume) was a determinant of VO2 peak (r2 = .33, p = .006). ATPmax (r2 = .158, p = .03) and VO2 peak (r2 = .475, p < .0001) were correlated with preferred walking speed. Inclusion of both ATPmax/St3 and VO2 peak in a multiple linear regression model improved the prediction of preferred walking speed (r2 = .647, p < .0001), suggesting that mitochondrial efficiency is an important determinant for preferred walking speed. Conclusions. Lower mitochondrial capacity and efficiency were both associated with slower walking speed within a group of older participants with a wide range of function. In addition to aerobic capacity, lower mitochondrial capacity and efficiency likely play roles in slowing gait speed with age. [ABSTRACT FROM PUBLISHER]

Background. Obesity-related increases in multiple inflammatory markers may contribute to the persistent subclinical inflammation common with advancing age. However, it is unclear if a specific combination of markers reflects the underlying inflammatory state. We used factor analysis to identify inflammatory factor(s) and examine their associations with adiposity in older adults at risk for disability. Methods. Adiponectin, CRP, IL-1ra, IL-1sRII, IL-2sRα, IL-6, IL-6sR, IL-8, IL-15, sTNFRI, sTNFRII, and TNF-α were measured in 179 participants from the Lifestyle Interventions and Independence for Elders Pilot (Mean ± SD age 77 ± 4 years, 76% white, 70% women). Body mass index, waist circumference, and total fat mass were assessed by anthropometry and dual-energy x-ray absorptiometry. Results. IL-2sRα, sTNFRI, and sTNFRII loaded highest on the first factor (factor 1). CRP, IL-1ra, and IL-6 loaded highest on the second factor (factor 2). Factor 2, but not factor 1, was positively associated with 1-SD increments in waist circumference (β = 0.160 ± 0.057, p = .005), body mass index (β = 0.132 ± 0.053, p = .01), and total fat mass (β = 0.126 ± 0.053, p = .02) after adjusting for age, gender, race/ethnicity, site, smoking, anti-inflammatory medications, comorbidity index, health-related quality of life, and physical function. These associations remained significant after further adjustment for grip strength, but only waist circumference remained associated with inflammation after adjusting for total lean mass. There were no significant interactions between adiposity and muscle mass or strength for either factor. Conclusions. Greater total and abdominal adiposity are associated with higher levels of an inflammatory factor related to CRP, IL-1ra, and IL-6 in older adults, which may provide a clinically useful measure of inflammation in this population. [ABSTRACT FROM PUBLISHER]

Background. There is a lack of information on whether exercise training alone can reduce the prevalence of metabolic syndrome (MetS) in elderly men and women. Methods. This study was an ancillary to the Lifestyle Interventions and Independence for Elders Pilot Study, a four-site, single-blind, randomized controlled clinical trial comparing a 12-month physical activity (PA) intervention (N = 180) with a successful aging intervention (N = 181) in elderly (70–89 years) community-dwelling men and women at risk for physical disability. The PA intervention included aerobic, strength, and flexibility exercises, with walking as the primary mode. MetS was defined using the National Cholesterol Education Program criteria. Results. There was no significant change in body weight or fat mass after either intervention. The trend of MetS prevalence over the intervention period was similar between PA and successful aging groups (p = .77). Overall, the prevalence of MetS decreased significantly from baseline to 6 months (p = .003) but did not change further from 6- to 12-month visits (p = .11). There were no group differences in any individual MetS components (p > .05 for all group by visit interactions). However, in individuals not using medications at any visit to treat MetS components, those in the PA intervention had lower odds of having MetS than those in the successful aging group during follow-up (odds ratio = 0.28, 95% confidence interval = 0.08–0.96). Conclusions. In this sample, a 12-month PA intervention did not reduce the prevalence of MetS more than a successful aging intervention, perhaps due to the large proportion of individuals taking medications for treating MetS components. [ABSTRACT FROM PUBLISHER]

Background: Objective methods to measure daily energy expenditure in studies of aging are needed. We sought to determine the accuracy of total energy expenditure (TEE) and activity energy expenditure (AEE) estimates from the SenseWear Pro armband (SWA) using software versions 6.1 (SWA 6.1) and 5.1 (SWA 5.1) relative to criterion methods in free-living older adults.Methods: Participants (n = 19, mean age 82.0 years) wore a SWA for a mean ± SD 12.5 ± 1.1 days, including while sleeping. During this same period, criterion values for TEE were assessed with doubly labeled water and for resting metabolic rate (RMR) with indirect calorimetry. AEE was calculated as 0.9 TEE - RMR.Results: For TEE, there was no difference in mean ± SD values from doubly labeled water (2,040 ± 472 kcal/day) versus SWA 6.1 (2,012 ± 497 kcal/day, p = .593) or SWA 5.1 (2,066 ± 474 kcal/day, p = .606); individual values were highly correlated between methods (SWA 6.1 r = .893, p < .001; SWA 5.1 r = .901, p < .001) and demonstrated strong agreement (SWA 6.1 intraclass correlation coefficient = .896; SWA 5.1 intraclass correlation coefficient = .904). For AEE, mean values from SWA 6.1 (427 ± 304 kcal/day) were lower by 26.8% than criterion values (583 ± 242 kcal/day, p = .003), and mean values from SWA 5.1 (475 ± 299 kcal/day) were lower by 18.5% than criterion values (p = .021); however, individual values were highly correlated between methods (SWA 6.1 r = .760, p < .001; SWA 5.1 r = .786, p < .001) and demonstrated moderate agreement (SWA 6.1 intraclass correlation coefficient = .645; SWA 5.1 intraclass correlation coefficient = .720). Bland-Altman plots identified no systematic bias for TEE or AEE.Conclusions: Acceptable levels of agreement were observed between SWA and criterion measurements of TEE and AEE in older adults. [ABSTRACT FROM AUTHOR]

Background. Chronic kidney disease (CKD) is associated with insulin resistance (IR). Prior studies have found that in individuals with CKD, leptin is associated with fat mass but resistin is not and the associations with adiponectin are conflicting. This suggests that the mechanism and factors associated with IR in CKD may differ.Methods. Of the 2418 individuals without reported diabetes at baseline, participating in the Health, Aging and Body Composition study, a study in older individuals aged 70–79 years, 15.6% had CKD defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 based on cystatin C. IR was defined as the upper quartile of the homeostasis model assessment. The association of visceral and subcutaneous abdominal fat, percent body fat, muscle fat, lipids, inflammatory markers and adiponectin were tested with logistic regression. Interactions were checked to assess whether the factors associated with IR were different in those with and without CKD.Results. Individuals with IR had a lower eGFR (80.7 ± 20.9 versus 75.6 ± 19.6, P < 0.001). After multivariable adjustment, eGFR (odds ratio per 10 mL/min/1.73m2 0.92, 95% confidence interval 0.87–0.98) and CKD (1.41, 1.04–1.92) remained independently associated with IR. In individuals with and without CKD, the significant predictors of IR were male sex, black race, higher visceral fat, abdominal subcutaneous fat and triglycerides. In individuals without CKD, IR was associated with lower high-density lipoprotein and current nonsmoking status in multivariate analysis. In contrast, among individuals with CKD, interleukin-6 (IL-6) was independently associated with IR. There was a significant interaction of eGFR with race and IL-6 with a trend for adionectin but no significant interactions with CKD (P > 0.1). In the fully adjusted model, there was a trend for an interaction with adiponectin for eGFR (P = 0.08) and significant for CKD (P = 0.04 ), where adiponectin was associated with IR in those without CKD but not in those with CKD.Conclusions. In mainly Stage 3 CKD, kidney function is associated with IR; except for adiponectin, the correlates of IR are similar in those with and without CKD. [ABSTRACT FROM PUBLISHER]

Background. An excessive amount of adipose tissue may contribute to sarcopenia and may be one mechanism underlying accelerated loss of muscle mass and strength with aging. We therefore examined the association of baseline total body fat with changes in leg lean mass, muscle strength, and muscle quality over 7 years of follow-up and whether this link was explained by adipocytokines and insulin resistance. Methods. Data were from 2,307 men and women, aged 70–79 years, participating in the Health, Aging, and Body Composition study. Total fat mass was acquired from dual energy X-ray absorptiometry. Leg lean mass was assessed by dual energy X-ray absorptiometry in Years 1, 2, 3, 4, 5, 6, and 8. Knee extension strength was measured by isokinetic dynamometer in Years 1, 2, 4, 6, and 8. Muscle quality was calculated as muscle strength divided by leg lean mass. Results. Every SD greater fat mass was related to 1.3 kg more leg lean mass at baseline in men and 1.5 kg in women (p < .01). Greater fat mass was also associated with a greater decline in leg lean mass in both men and women (0.02 kg/year, p < .01), which was not explained by higher levels of adipocytokines and insulin resistance. Larger fat mass was related to significantly greater muscle strength but significantly lower muscle quality at baseline (p < .01). No significant differences in decline of muscle strength and quality were found. Conclusions. High fatness was associated with lower muscle quality, and it predicts accelerated loss of lean mass. Prevention of greater fatness in old age may decrease the loss of lean mass and maintain muscle quality and thereby reducing disability and mobility impairments. [ABSTRACT FROM PUBLISHER]

Background: Previous cross-sectional studies demonstrate positive associations of fat-free mass and negative associations of centrally distributed fat deposits with respiratory function in older adults. Few studies have evaluated whether greater losses of muscle and increases in fat are associated with more rapid decline in respiratory function in aging.Methods: Nine hundred and fifty-seven men and 1,024 women aged, respectively, 73.6 ± 2.8 years and 73.2 ± 2.8 years at baseline were followed for 5 years. Body weight, waist circumference, bone mineral density, fat-free mass, fat mass and fat mass percentage as measured by DXA, abdominal subcutaneous and visceral adipose tissue, thigh muscle area, thigh intermuscular fat by CT and forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were evaluated at baseline and after 5-years follow-up.Results: Cross-sectional analyses showed that height and thigh muscle area were positively and visceral adipose tissue negatively related to FEV1 and FVC. Increase in fat mass over five years was associated with concurrent FEV1 and FVC decline. In analyses stratified by weight-change categories, men and women who gained weight (vs stable/lost weight) had more rapid declines in FEV1 and FVC.Conclusion: In this well-functioning cohort, less muscle and greater abdominal fat were each associated with poorer lung spirometry cross-sectionally, whereas increase in fat mass over 5 years was associated with concurrent FEV1 and FVC decline. Weight gain and accompanying fat deposition may accelerate age-related declines in respiratory function. [ABSTRACT FROM AUTHOR]

Background: Aging is associated with a loss of muscle mass and increased body fat. The effects of diet-induced weight loss on muscle mass in older adults are not clear.Purpose: This study examined the effects of diet-induced weight loss, alone and in combination with moderate aerobic exercise, on skeletal muscle mass in older adults.Methods: Twenty-nine overweight to obese (body mass index = 31.8 +/- 3.3 kg/m(2)) older (67.2 +/- 4.2 years) men (n = 13) and women (n = 16) completed a 4-month intervention consisting of diet-induced weight loss alone (WL; n = 11) or with exercise (WL/EX; n = 18). The WL intervention consisted of a low-fat, 500-1,000 kcal/d caloric restriction. The WL/EX intervention included the WL intervention with the addition of aerobic exercise, moderate-intensity walking, three to five times per week for 35-45 minutes per session. Whole-body dual-energy x-ray absorptiometry, thigh computed tomography (CT), and percutaneous muscle biopsy were performed to assess changes in skeletal muscle mass at the whole-body, regional, and cellular level, respectively.Results: Mixed analysis of variance demonstrated that both groups had similar decreases in bodyweight (WL, -9.2% +/- 1.0%; WL/EX, -9.1% +/- 1.0%) and whole-body fat mass (WL, -16.5%, WL/EX, -20.7%). However, whole-body fat-free mass decreased significantly (p < .05) in WL (-4.3% +/- 1.2%) but not in WL/EX (-1.1% +/- 1.0%). Thigh muscle cross-sectional area by CT decreased in both groups (WL, -5.2% +/- 1.1%; WL/EX, -3.0% +/- 1.0%) and was not statistically different between groups. Type I muscle fiber area decreased in WL (-19.2% +/- 7.9%, p = .01) but remained unchanged in WL/EX (3.4% +/- 7.5%). Similar patterns were observed in type II fibers (WL, -16.6% +/- 4.0%; WL/EX, -0.2% +/- 6.5%).Conclusion: Diet-induced weight loss significantly decreased muscle mass in older adults. However, the addition of moderate aerobic exercise to intentional weight loss attenuated the loss of muscle mass. [ABSTRACT FROM AUTHOR]

Background. The metabolic syndrome includes dyslipidemia, abdominal obesity, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cerebrovascular disease (CVD), but consequences beyond these outcomes have not been examined extensively. We investigated whether metabolic abnormalities have independent con- sequences on loss of mobility function of older persons. Methods. Data are from 2,920 men and women, 70-79 years, participating in the Health ABC study without mobility limitations at baseline. Metabolic syndrome was defined as ⩾3 of the following: (a) waist circumference >102 (men) or >88cm (women); (b) triglycerides ⩾150 mg/dL; (c) high-density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women); (d) blood pressure ⩾130/85 mm Hg or antihypertensive medication; and (d) fasting glucose ⩾110 mg/dL or antidiabetic medication. Mobility limitation was defined as difficulty or inability walking ¼ mile or climbing 10 steps during two consecutive semiannual assessments over 4.5 years. Results. The prevalence of metabolic syndrome was 38.6%. The metabolic syndrome was associated with an adjusted relative risk (RR) of 1.46 (95% confidence interval [CI]= 1.30-1.63) for developing mobility limitations. The risk increased when more metabolic syndrome components were present (p trend >.001). All metabolic syndrome components were significantly associated with incident mobility limitations with the highest RRs for abdominal obesity (RR= 1.54, 95% Cl= 1.35-1.75) and hyperglycemia (RR= 1.44, 95% CI= 1.27-1.63). Findings were unchanged when persons with baseline, or incident, CVD, stroke, or diabetes were excluded. Conclusions. Metabolic syndrome abnormalities, especially abdominal obesity and hyperglycemia, are predictive of mobility limitations in the elderly, independent of CVD or diabetes. [ABSTRACT FROM AUTHOR]

Background. It is unclear if physical activity (PA) can prevent or reverse frailty. We examined different doses and types of PA and their association with the onset and severity of frailty. Methods. Health, Aging and Body Composition (Health ABC) study participants (N = 2,964) were followed for 5 years, with frailty defined as a gait speed of less than 0.60 m/s and/or inability to rise from a chair without using one's arms. Individuals with one impairment were considered moderately frail and those with both severely frail. We examined PA doses of volume and intensity, activity types (eg, lifestyle vs exercise activities), and their associations with incident frailty and transition to severe frailty in those who became frail. Results. Adjusted models indicated that sedentary individuals had significantly increased odds of developing frailty com- pared with the exercise active group (adjusted odds ratio [OR] = 1.45; 95% confidence interval [Cl]: 1.04-2.01), whereas the lifestyle active did not. Number of diagnoses was the strongest predictor of incident frailty. In those who became frail during follow-up (a = 410), there was evidence that the sedentary (adjusted OR = 2.80; 95% Cl: 0.98-8.02) and lifestyle active (adjusted OR = 2.81; 95% CI: I .22-6.43) groups were more likely to have worsening frailty over time. Conclusions. Despite the strong relationship seen between comorbid conditions and onset of frailty, this observational study suggests that participation in self-selected exercise activities is independently associated with delaying the onset and the progression of frailty. Regular exercise should be further examined as a potential factor in frailty prevention for older adults. [ABSTRACT FROM AUTHOR]

Background: Mobility limitations are prevalent, potentially reversible precursors to mobility loss that may go undetected in older adults. This study evaluates standardized administration of an endurance walk test for identifying unrecognized and impending mobility limitation in community elders.Methods: Men and women (1480 and 1576, respectively) aged 70-79 years with no reported mobility limitation participating in the Health, Aging and Body Composition study were administered the Long Distance Corridor Walk. Walk performance was examined to determine unrecognized mobility deficits at baseline and predict new self-recognition of mobility limitation within 2 years.Results: On testing, 23% and 36% of men and women evidenced mobility deficits defined as a contraindication to exertion, meeting stopping criteria or exceeding 7 minutes to walk 400 m. Unrecognized deficits increased with age and were more prevalent in blacks, smokers, obese individuals, and infrequent walkers. Within 2 years, 21% and 34% of men and women developed newly recognized mobility limitation; those with baseline unrecognized deficits had higher rates, 40% and 54% (p <.001), respectively. For each additional 30 seconds over 5 minutes needed to walk 400 m, likelihood of newly recognized mobility limitation increased by 65% and 37% in men and women independent of age, race, obesity, smoking status, habitual walking, reported walking ease, and usual gait speed.Conclusions: A sizable proportion of elders who report no walking difficulty have observable deficits in walking performance that precede and predict their recognition of mobility limitation. Endurance walk testing can help identify these deficits and provide the basis for treatment to delay progression of mobility loss. [ABSTRACT FROM AUTHOR]

Background: Circulating levels of adipokines are elevated with adiposity and are closely linked with the clustering of traditional metabolic risk factors for cardiovascular disease. The purpose of this study was to examine the relationship of metabolic syndrome to several adipokines and the role of total and visceral adiposity in influencing this relationship in older adults.Methods: A cross-sectional analysis was conducted including 1914 individuals aged 70-79 years without cardiovascular disease or type 2 diabetes. The metabolic syndrome was defined by the updated Adult Treatment Panel III criteria. Circulating levels of leptin, adiponectin, plasminogen activator inhibitor type 1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) were measured. Body composition and abdominal visceral fat area were determined.Results: Both the presence of metabolic syndrome and the number of metabolic syndrome components were associated with higher levels of leptin, PAI-1, IL-6, TNF-alpha, and CRP and with lower levels of adiponectin (all p <.0001). The odds ratios for the prevalence of metabolic syndrome associated with adipokines were attenuated after adjustment for total fat mass and/or visceral fat area, but remained significant. Levels of leptin, PAI-1, IL-6, and TNF-alpha were higher (all p <.05 to p <.0001), and adiponectin was lower (all p <.0001), in persons with, compared to those without, metabolic syndrome within each tertile of percent body fat.Conclusion: The metabolic syndrome is associated with adipokines in older adults across a wide range of adiposity, including in those with low or normal overall fatness. [ABSTRACT FROM AUTHOR]

Background. Circulating levels of adipokines are elevated with adiposity and are closely linked with the clustering of traditional metabolic risk factors for cardiovascular disease. The purpose of this study was to examine the relationship of metabolic syndrome to several adipokines and the role of total and visceral adiposity in influencing this relationship in older adults. Methods. A cross-sectional analysis was conducted including 1914 individuals aged 70-79 years without cardiovascular disease or type 2 diabetes. The metabolic syndrome was defined by the updated Adult Treatment Panel HI criteria. Circulating levels of leptin, adiponectin, plasminogen activator inhibitor type 1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured. Body composition and abdominal visceral fat area were determined. Results. Both the presence of metabolic syndrome and the number of metabolic syndrome components were associated with higher levels of leptin, PAI-1, IL-6, TNF-α, and CRP and with lower levels of adiponectin (all p < .0001). The odds ratios for the prevalence of metabolic syndrome associated with adipokines were attenuated after adjustment for total fat mass and/or visceral fat area, but remained significant. Levels of leptin, PAI-1, IL-6, and TNF-α were higher (all p < .05 to p < .0001), and adiponectin was lower (all p < .0001), in persons with, compared to those without, metabolic syndrome within each tertile of percent body fat. Conclusion. The metabolic syndrome is associated with adipokines in older adults across a wide range of adiposity, including in those with low or normal overall fatness. [ABSTRACT FROM AUTHOR]

Background and Purpose Muscle atrophy is common in patients with rheumatoid arthritis (RA). Although neuromuscular electrical stimulation (NMES) is a viable treatment for muscle atrophy, there is no evidence about the use of NMES in patients with RA. The purposes of this multiple-patient case report are: (1) to describe the use of NMES applied to the quadriceps femoris muscles in conjunction with an exercise program in patients with RA; (2) to report on patient tolerance and changes in lean muscle mass, quadriceps femoris muscle strength (force-producing capacity), and physical function; and (3) to explore how changes in muscle mass relate to changes in quadriceps femoris muscle strength, measures of physical function, and patient adherence. Case Description Seven patients with RA (median age=61 years, range=39-80 years) underwent 16 weeks of NMES and volitional exercises. Lean muscle mass and strength of the quadriceps femoris muscle and physical function were measured before and after treatment. Outcomes One patient did not tolerate the NMES treatment, and 2 patients did not complete at least half of the proposed treatment. Patients who completed the NMES and volitional exercise program increased their lean muscle mass, muscle strength, and physical function. Discussion Because of the small sample, whether NMES combined with exercises is better than exercise alone or NMES alone could not be determined. However, the outcomes from this multiple-patient case report indicate that NMES is a viable treatment option to address muscle atrophy and weakness in patients with RA. Strategies to increase tolerance and adherence to NMES are warranted. [ABSTRACT FROM AUTHOR]

Background. The loss of muscle mass is considered to be a major determinant of strength loss in aging. However, large-scale longitudinal studies examining the association between the loss of mass and strength in older adults are lacking. Methods. Three-year changes in muscle mass and strength were determined in 1880 older adults in the Health, Aging and Body Composition Study. Knee extensor strength was measured by isokinetic dynamometry. Whole body and appendicular lean and fat mass were assessed by dual-energy x-ray absorptiometry and computed tomography. Results. Both men and women lost strength, with men losing almost twice as much as women. Blacks lost about 28% more strength than did whites. Annualized rates of leg strength decline (3.4% in white men, 4.1% in black men. 2.6% in white women, and 3.0% in black women) were about three times greater than the rates of loss of leg lean mass (∼1% per year). The loss of lean mass, as well as higher baseline strength, lower baseline leg lean mass, and older age, was dependently associated with strength decline in both men and women. However, gain of lean mass was not accompanied by strength maintenance or gain (ß coefficients; men, -0.84 ± 4.61, p = .92, women, -1.68 ± 3.57, p = .64) Conclusions. Although the loss of muscle mass is associated with the decline in strength in older adults, this strength decline is much more rapid than the concominant loss of muscle mass, suggesting a decline in muscle quality. Moreover, maintaining or gaining muscle does not prevent aging-associated declines in muscle strength. [ABSTRACT FROM AUTHOR]

Skeletal muscle mitochondria are implicated with age-related loss of function and insulin resistance. We examined the effects of exercise on skeletal muscle mitochondria in older (age 67.3 ± 0.6 years) men (n = 5) and women (n = 3). Similar increases in (p < .01) cardiolipin (88.2 ± 9.0 to 130.6 + 7.5 µg/mU creatine kinase activity [CK]) and the total mitochondrial DNA (1264 ± 170 to 1895 ± 273 copies per diploid of nuclear genome) reflected increased mitochondria content. Succinate oxidase activity, complexes 2-4 of the electron transport chain (ETC), increased from 0. 13 ± 0.02 to 0.20 ± 0.02 U/mU CK (p < .01). This improvement was more pronounced (p < .05) in subsarcolemmal (127 ± 48%) compared to intennyofibrillar (56 ± 12%) mitochondria. NADH oxidase activity, representing total ETC activity, increased from 0.51 ± 0.09 to 1.00 ± 0.09 U/mU CK (p < .01). In conclusion, exercise enhances mitochondria ETC activity in older human skeletal muscle, particularly in subsarcolemmal mitochondria, which is likely related to the concomitant increases in mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Background: Although muscle strength and mass are highly correlated, the relationship between direct measures of low muscle mass (sarcopenia) and strength in association with mortality has not been examined.Methods: Total mortality rates were examined in the Health, Aging and Body Composition (Health ABC) Study in 2292 participants (aged 70-79 years, 51.6% women, and 38.8% black). Knee extension strength was measured with isokinetic dynamometry, grip strength with isometric dynamometry. Thigh muscle area was measured by computed tomography (CT) scan, and leg and arm lean soft tissue mass were determined by dual energy x-ray absorptiometry (DXA). Both strength and muscle size were assessed as in gender-specific Cox proportional hazards models, with age, race, comorbidities, smoking status, level of physical activity, fat area by CT or fat mass by DXA, height, and markers of inflammation, including interleukin-6, C-reactive protein, and tumor necrosis factor-alpha considered as potential confounders.Results: There were 286 deaths over an average of 4.9 (standard deviation = 0.9) years of follow-up. Both quadriceps and grip strength were strongly related to mortality. For quadriceps strength (per standard deviation of 38 Nm), the crude hazard ratio for men was 1.51 (95% confidence interval, 1.28-1.79) and 1.65 (95% confidence interval, 1.19-2.30) for women. Muscle size, determined by either CT area or DXA regional lean mass, was not strongly related to mortality. In the models of quadriceps strength and mortality, adjustment for muscle area or regional lean mass only slightly attenuated the associations. Further adjustment for other factors also had minimal effect on the association of quadriceps strength with mortality. Associations of grip strength with mortality were similar.Conclusion: Low muscle mass did not explain the strong association of strength with mortality, demonstrating that muscle strength as a marker of muscle quality is more important than quantity in estimating mortality risk. Grip strength provided risk estimates similar to those of quadriceps strength. [ABSTRACT FROM AUTHOR]

Background: Lower muscle mass has been correlated with poor physical function; however, no studies have examined this relationship prospectively. This study aims to investigate whether low muscle mass, low muscle strength, and greater fat infiltration into the muscle predict incident mobility limitation.Methods: Our study cohort included 3075 well-functioning black and white men and women aged 70-79 years participating in the Health, Aging, and Body Composition study. Participants were followed for 2.5 years. Muscle cross-sectional area and muscle tissue attenuation (a measure of fat infiltration) were measured by computed tomography at the mid-thigh, and knee extensor strength by using a KinCom dynamometer. Incident mobility limitation was defined as two consecutive self-reports of any difficulty walking one-quarter mile or climbing 10 steps.Results: Mobility limitations were developed by 22.3% of the men and by 31.8% of the women. Cox's proportional hazards models, adjusting for demographic, lifestyle, and health factors, showed a hazard ratio of 1.90 [95% confidence interval (CI), 1.27-2.84] in men and 1.68 (95% CI, 1.23-2.31) in women for the lowest compared to the highest quartile of muscle area (p <.01 for trend). Results for muscle strength were 2.02 (95% CI, 1.39-2.94) and 1.91 (95% CI, 1.41-2.58), p <.001 trend, and for muscle attenuation were 1.91 (95% CI, 1.31-2.83) and 1.68 (95% CI, 1.20-2.35), p <.01 for trend. When included in one model, only muscle attenuation and muscle strength independently predicted mobility limitation (p < .05). Among men and women, associations were similar for blacks and whites.Conclusion: Lower muscle mass (smaller cross-sectional thigh muscle area), greater fat infiltration into the muscle, and lower knee extensor muscle strength are associated with increased risk of mobility loss in older men and women. The association between low muscle mass and functional decline seems to be a function of underlying muscle strength. [ABSTRACT FROM AUTHOR]

Background: A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show a relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers of inflammation are associated with muscle mass and strength in well-functioning elderly persons.Methods: We used baseline data (1997-1998) of the Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed tomography), appendicular muscle mass (dual-energy x-ray absorptiometry), isokinetic knee extensor strength (KinCom), and isometric grip strength were measured. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by enzyme-linked immunosorbent assay (ELISA).Results: Higher cytokine levels were generally associated with lower muscle mass and lower muscle strength. The most consistent relationship across the gender and race groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip strength was 1.1 to 2.4 kg lower (p <.05) after adjustment for age, clinic site, health status, medications, physical activity, smoking, height, and body fat. An overall measure of elevated cytokine level was created by combining the levels of IL-6 and TNF-alpha. With the exception of white men, elderly persons having high levels of IL-6 (>1.80 pg/ml) as well as high levels of TNF-alpha (>3.20 pg/ml) had a smaller muscle area, less appendicular muscle mass, a lower knee extensor strength, and a lower grip strength compared to those with low levels of both cytokines.Conclusions: Higher plasma concentrations of IL-6 and TNF-alpha are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels, as often observed in healthy older persons, may contribute to the loss of muscle mass and strength that accompanies aging. [ABSTRACT FROM AUTHOR]