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Performance fatigability is typically experienced as insufficient energy to complete daily physical tasks, particularly with advancing age, often progressing toward dependency. Thus, understanding the etiology of performance fatigability, especially cellular-level biological mechanisms, may help to delay the onset of mobility disability. We hypothesized that skeletal muscle energetics may be important contributors to performance fatigability. Participants in the Study of Muscle, Mobility and Aging completed a usual-paced 400-m walk wearing a wrist-worn ActiGraph GT9X to derive the Pittsburgh Performance Fatigability Index (PPFI, higher scores = more severe fatigability) that quantifies percent decline in individual cadence-versus-time trajectory from their maximal cadence. Complex I&II-supported maximal oxidative phosphorylation (max OXPHOS) and complex I&II-supported electron transfer system (max ETS) were quantified ex vivo using high-resolution respirometry in permeabilized fiber bundles from vastus lateralis muscle biopsies. Maximal adenosine triphosphate production (ATP max ) was assessed in vivo by 31 P magnetic resonance spectroscopy. We conducted tobit regressions to examine associations of max OXPHOS, max ETS, and ATP max with PPFI, adjusting for technician/site, demographic characteristics, and total activity count over 7-day free-living among older adults (N = 795, 70-94 years, 58% women) with complete PPFI scores and ≥1 energetics measure. Median PPFI score was 1.4% [25th-75th percentile: 0%-2.9%]. After full adjustment, each 1 standard deviation lower max OXPHOS, max ETS, and ATP max were associated with 0.55 (95% CI: 0.26-0.84), 0.39 (95% CI: 0.09-0.70), and 0.54 (95% CI: 0.27-0.81) higher PPFI score, respectively. Our findings suggested that therapeutics targeting muscle energetics may potentially mitigate fatigability and lessen susceptibility to disability among older adults., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

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 (rs) 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 (rs = -0.75), SPPB score (rs = -0.38), chair stand speed (rs = -0.36), leg peak power (rs = -0.34) and VO2peak (rs = -0.40), and less strongly with perceived fatigability (rs = 0.28-0.29), all p < .001. PPFI score was not correlated with mood (|rs| < 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., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Individuals are often counseled to use behavioral weight loss strategies to reduce risk for cardiovascular disease (CVD). We examined whether any benefits for CVD risk from weight loss intervention extend uniformly to individuals across a range of underlying health states., Methods: The time until first occurrence of a composite of fatal and nonfatal myocardial infarction and stroke, hospitalized angina, or CVD death was analyzed from 8 to 11 years of follow-up of 4,859 adults who were overweight or obese, aged 45-76 years with Type 2 diabetes. Individuals had been randomly assigned to either an intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Participants were grouped by intervention assignment and a frailty index (FI) based on deficit accumulation, ordered from fewer (first tertile) to more (third tertile) deficits., Results: Baseline FI scores were unrelated to intervention-induced weight losses and increased physical activity. The relative effectiveness of ILI on CVD incidence was inversely related to baseline FI in a graded fashion (p = .01), with relative benefit (hazard ratio = 0.73 [95% CI 0.55,0.98]) for individuals in the first FI tertile to no benefit (hazard ratio = 1.15 [0.94,1.42]) among those in the third FI tertile. This graded relationship was not seen for individuals ordered by age tertile (p = .52), and was stronger among participants aged 45-59 years (three-way interaction p = .04)., Conclusions: In overweight/obese adults with diabetes, multidomain lifestyle interventions may be most effective in reducing CVD if administered before individuals have accrued many age-related health deficits. However, these exploratory analyses require confirmation by other studies., Clinical Trial Registration: NCT00017953., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study aimed to examine change in bone mineral density (BMD) and trabecular bone score among older adult weight regainers (WR) and weight maintainers (WM)., Methods: Observational data come from 77 older adults (mean age: 67 [SD 5] years; 69% women; 70% white) with obesity (mean BMI: 33.6 [SD  3.7] kg/m 2 ) who lost weight during an 18-month weight loss intervention. Total body mass and body composition, along with regional (total hip, femoral neck, lumbar spine) BMD and trabecular bone score, were measured at baseline, 18 months, and 30 months. WR (n = 36) and WM (n = 41) categories were defined as a ≥ 5% or < 5% weight gain from 18 to 30 months, respectively., Results: Among skeletal indices, only total hip BMD was significantly reduced during the 18-month intervention period in both WRs (-3.9%; 95% CI: -5.8% to -2.0%) and WMs (-2.4%; 95% CI: -4.3% to -0.5%; P = 0.07). After adjustment for relevant baseline covariates and weight change from 0 to 18 months, 30-month change in total hip BMD was -2.6% (95% CI: -4.3% to -0.9%) and -3.9% (95% CI: -5.7% to -2.1%) among WRs and WMs, respectively (P = 0.07)., Conclusions: Loss of hip BMD persists in the year after a weight loss intervention among older adults with obesity, regardless of weight regain status., (© 2019 The Obesity Society.)

Background: The movement profile of older adults with compromised function is unknown, as is the relationship between these profiles and the development of major mobility disability (MMD)-a critical clinical outcome. We first describe the dimensions of movement in older adults with compromised function and then examine whether these dimensions predict the onset of MMD., Methods: Older adults at risk for MMD (N = 1,022, mean age = 78.7 years) were randomized to receive a structured physical activity intervention or health education control. We assessed MMD in 6-month intervals (average follow-up of 2.2 years until incident MMD), with activity assessed at baseline, 6-, 12- and 24-month follow-up via accelerometry., Results: A principal components analysis of 11 accelerometer-derived metrics yielded three components representing lifestyle movement (LM), extended bouts of moderate-to-vigorous physical activity (MVPA), and stationary body posture. LM accounted for the greatest proportion of variance in movement (53%). Within health education, both baseline LM (HR = 0.74; 95% CI 0.62 to 0.88) and moderate-to-vigorous physical activity (HR = 0.69; 95% CI 0.54 to 0.87) were associated with MMD, whereas only LM was associated with MMD within physical activity (HR = 0.74; 95% CI 0.61 to 0.89). There were similar nonlinear relationships present for LM in both physical activity and health education (p < .04), whereby risk for MMD was lower among individuals with higher levels of LM., Conclusions: Both LM and moderate-to-vigorous physical activity should be central in treatment regimens for older adults at risk for MMD., Trial Registration: clinicaltrials.gov Identifier NCT01072500., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ample evidence implicates cellular senescence as a contributor to frailty and functional decline in rodents, but considerable effort remains to translate these findings to human aging., Methods: We quantified senescence biomarker p16INK4a-expressing cells in thigh adipose tissue obtained from older women previously enrolled in a 5-month resistance training intervention, with or without caloric restriction (RT ± CR, n = 11 baseline, 8 pre-post-intervention pairs). Women in this subsample were older (72.9 ± 3.4 y) and overweight/obese (body mass index: 30.6 ± 2.4 kg/m2). p16INK4a+ cells were identified from 12 to 20 random visual fields/sample at 20× magnification (immunohistochemical, nuclear staining) and were present in all adipose samples., Results: Cross-sectional associations were observed between p16INK4a+ cell burden and physical function, including grip strength (r = -0.74), 400-m walk time (r = 0.74), 4-m gait speed (r = -0.73), and self-perceived mobility (r = -0.78) (p ≤ .05). These relationships remained significant after independent adjustments for age and adiposity (p ≤ .05). p16INK4a+ cell abundance was lower following the intervention (pre: 5.47 ± 3.4%, post: 2.17 ± 1.1% count p16INK4a+ cells, p ≤ .05)., Conclusions: These results provide proof-of-concept that p16INK4a+ cells in thigh adipose are associated with physical function, and may be sensitive to change with RT ± CR in overweight/obese older women.

Background: To examine the effect of exercise modality during weight loss on hip and spine bone mineral density (BMD) in overweight and obese, older adults., Methods: This analysis compared data from two 5-month, randomized controlled trials of caloric restriction (CR; inducing 5-10% weight loss) with either resistance training (RT) or aerobic training (AT) in overweight and obese, older adults. Participants in the RT + CR study underwent 3 days/week of 8 upper/lower body exercises (3 sets, 10 repetitions at 70% 1 RM) and participants in the AT+CR study underwent 4 days/week of treadmill walking (30 min at 65-70% heart rate reserve). BMD at the total hip, femoral neck, and lumbar spine was assessed via dual-energy X-ray absorptiometry at baseline and 5 months., Results: A total of 123 adults (69.4 ± 3.5 years, 67% female, 81% Caucasian) participated in the RT+CR (n = 60) and AT+CR (n = 63) interventions. Average weight loss was 5.7% (95% CI: 4.6-6.7%) and 8.2% (95% CI: 7.2-9.3%) in RT+CR and AT+CR groups, respectively. After adjustment for age, gender, race, baseline BMI and BMD, and weight change, differential treatment effects were observed for total hip and femoral neck (both p < .05), but not lumbar spine. Total hip (1.83 [-3.90, 7.55] mg/cm2) and femoral neck (9.14 [-0.70, 18.98] mg/cm2) BMD was unchanged in RT+CR participants, and modestly decreased in AT+CR participants (total hip: -7.01 [-12.73, -1.29] mg/cm2; femoral neck: -5.36 [-14.92, 4.20] mg/cm2)., Conclusions: Results suggest performing resistance, rather than aerobic, training during CR may attenuate loss of hip and femoral neck BMD in overweight and obese older adults. Findings warrant replication from a long-term, adequately powered, RCT., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP). These processes synergistically promote chronic sterile inflammation, insulin resistance, and lipid redistribution away from subcutaneous adipose tissue. Without intervention, these effects contribute to age-related systemic metabolic dysfunction, physical limitations, and frailty. Thus adipose tissue dysfunction may be a fundamental contributor to the elevated risk of chronic disease, disability, and adverse health outcomes with advancing age., (©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.)

Background: Evidence implicates the amount and location of fat in aging-related loss of muscle function; however, whether intramyocellular lipids affect muscle contractile capacity is unknown., Methods: We compared both in vivo knee extensor muscle strength, power, and quality and in vitro mechanical properties of vastus lateralis single-muscle fibers between normal weight (NW) and obese older adults and determined the relationship between muscle lipid content (both intramuscular adipose tissue and intramyocellular lipids) and in vivo and in vitro muscle function in NW and obese individuals., Results: The obese group had a greater percentage of type-I fibers compared to the NW group. The cross-sectional area of type-I fibers was greater in obese compared to NW; however, maximal shortening velocity of type-I fibers in the obese was slower compared to NW. Type-I and type-IIa fibers from obese group produced lower specific force than that of type-I and type-IIa fibers from the NW group. Normalized power was also substantially lower (~50%) in type-I fibers from obese adults. The intramyocellular lipids data showed that total lipid droplet area, number of lipid droplets, and area fraction were about twofold greater in type-I fibers from the obese compared to the NW group. Interestingly, a significant inverse relationship between average number of lipid droplets and single-fiber unloaded shortening velocity, maximal velocity, and specific power was observed in obese participants. Additionally, muscle echointensity correlated with single-fiber specific force., Conclusions: These data indicate that greater intramyocellular lipids are associated with slower myofiber contraction, force, and power development in obese older adults., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Our primary objective was to determine the long-term effects of physical activity (PA) and weight loss (WL) on body composition in overweight/obese older adults. Secondarily, the association between change in body mass and composition on change in several cardiometabolic risk factors and mobility was evaluated., Design and Methods: 288 older (X ± SD: 67.0 ± 4.8 years), overweight/obese (BMI 32.8 ± 3.8 kg/m² ) men and women participated in this 18-month randomized, controlled trial. Treatment groups included PA + WL (n = 98), PA-only (n = 97), and a successful aging (SA) health education control (n = 93). DXA-acquired body composition measures (total body fat and lean mass), conventional biomarkers of cardiometabolic risk, and 400-m walk time were obtained at baseline and 18 months., Results: Fat mass was significantly reduced from (X ± SE) 36.5 ± 8.9 kg to 31.7 ± 9.0 kg in the PA + WL group (p < 0.01), but remained unchanged from baseline in the PA-only (-0.8 ± 3.8 kg) and SA (-0.0 ± 3.9 kg) group. Lean mass losses were three times greater in the PA + WL groups compared to PA-only or SA groups (-2.5 ± 2.8 kg vs. -0.7 ± 2.2 kg or -0.8 ± 2.4 kg, respectively; p < 0.01); yet due to a larger decrease in fat mass, percent lean mass was significantly increased over baseline in the PA + WL groups (2.1% ± 2.6%; p < 0.01). Fat mass loss was primarily responsible for WL-associated improvements in cardiometabolic risk factors, while reduction in body weight, regardless of compartment, was significantly associated with improved mobility., Conclusion: This 18-month PA + WL program resulted in a significant reduction in percent body fat with a concomitant increase in percent body lean mass. Shifts in body weight and composition were associated with favorable changes in clinical parameters of cardiometabolic risk and mobility. Moderate PA without WL had no effect on body composition., (Copyright © 2013 The Obesity Society.)

Background: The prevalence of obesity in older adults is increasing but concerns exist about the effect of weight loss on muscle function. Demonstrating that muscle strength and power are not adversely affected during "intentional" weight loss in older adults is important given the wide-ranging negative health effects of excess adiposity., Methods: Participants (N = 88; age = 70.6 ± 3.6 years; body mass index = 32.8 ± 4.5 kg/m(2)) were randomly assigned to one of four intervention groups: pioglitazone or placebo and resistance training (RT) or no RT, while undergoing intentional weight loss via a hypocaloric diet. Outcomes were leg press power and isometric knee extensor strength. Analysis of covariance, controlling for baseline values, compared follow-up means of power and strength according to randomized groups., Results: Participants lost an average of 6.6% of initial body mass, and significant declines were observed in fat mass, lean body mass, and appendicular lean body mass. Compared with women not randomized to RT, women randomized to RT had significant improvements in leg press power (p < .001) but not in knee extensor strength (p = 0.12). No significant differences between groups in change in power or strength from baseline were detected in men (both p > .25). A significant pioglitazone-by-RT interaction for leg press power was detected in women (p = .006) but not in men (p = .88)., Conclusions: In older overweight and obese adults, a hypocaloric weight loss intervention led to significant declines in lean body mass and appendicular lean body mass. However, in women assigned to RT, leg power significantly improved following the intervention, and muscle strength or power was not adversely effected in the other groups. Pioglitazone potentiated the effect of RT on muscle power in women but not in men; mechanisms underlying this sex effect remain to be determined.

Background: In older adults, every 0.1-m/s slower gait speed is associated with a 12% higher mortality. However, little research has identified risk factors for gait-speed decline., Objective: We assessed the association between several measures of body composition and age-related decline in gait speed., Design: Data were from 2306 older adults who were participating in the Health, Aging, and Body Composition cohort and were followed for 4 y (50% women; 38% black). Usual walking speed (m/s) over 20 m was measured in years 2 through 6, and the baseline and changes in several measures of body composition were included in mixed-effects models., Results: Gait speed declined by 0.06 ± 0.00 m/s over the 4-y period. Baseline thigh intermuscular fat predicted the annual gait-speed decline (±SE) in both men and women (-0.01 ± 0.00 and -0.02 ± 0.00 m/s per 0.57 cm(2), respectively; P < 0.01). In men, but not in women, this relation was independent of total body adiposity. In longitudinal analyses, changes in thigh intermuscular fat and total thigh muscle were the only body-composition measures that predicted gait-speed decline in men and women combined. When modeled together, every 5.75-cm(2) increase in thigh intermuscular fat was associated with a 0.01 ± 0.00-m/s decrease in gait speed, whereas every 16.92-cm(2) decrease in thigh muscle was associated with a 0.01 ± 0.00-m/s decrease in gait speed., Conclusions: High and increasing thigh intermuscular fat are important predictors of gait-speed decline, implying that fat infiltration into muscle contributes to a loss of mobility with age. Conversely, a decreasing thigh muscle area is also predictive of a decline in gait speed.

Background: Clinical recommendation of weight loss (WL) in older adults remains controversial, partially due to concerns regarding lean mass loss and potential loss of physical function. The purpose of this study is to determine the independent associations between changes in fat and lean mass and changes in physical function in older, overweight, and obese adults undergoing intentional WL., Methods: Data from three randomized-controlled trials of intentional WL in older adults with similar functional outcomes (short physical performance battery and Pepper assessment tool for disability) were combined. Analyses of covariance models were used to investigate relationships between changes in weight, fat, and lean mass (acquired using dual-energy x-ray absorptiometry) and changes in physical function., Results: Overall loss of body weight was -7.8 ± 6.1 kg (-5.6 ± 4.1 kg and -2.7 ± 2.4 kg of fat and lean mass, respectively). In all studies combined, after adjustment for age, sex, and height, overall WL was associated with significant improvements in self-reported mobility disability (p < .01) and walking speed (p < .01). Models including change in both fat and lean mass as independent variables found only the change in fat mass to significantly predict change in mobility disability (β[fat] = 0.04; p < .01) and walking speed (β[fat] = -0.01; p < .01)., Conclusions: Results from this study demonstrate that loss of body weight, following intentional WL, is associated with significant improvement in self-reported mobility disability and walking speed in overweight and obese older adults. Importantly, fat mass loss was found to be a more significant predictor of change in physical function than lean mass loss.

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.

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.

The prevalence of obesity among older adults has increased during the past 20 years and will affect both medical and social services. Along with an increased risk of cardiovascular disease, diabetes, and several cancers, obesity is associated with increased risk of physical and cognitive disability. However, relatively little attention has been given to the issue of weight management among community-dwelling older adults. Intentional weight loss in obese older adults has not been widely advocated by health care providers due to the uncertainty of whether the benefits outweigh the risks. Limited data in older adults show that intentional weight loss is effective in improving diabetes, cardiovascular risk factors, and physical function. This review describes the changes in body composition associated with aging, the consequences of obesity in older adults, and the effect of intentional weight loss on chronic disease risk factors and physical function. Recommendations for weight loss in obese older adults that minimize the likelihood of adverse effects on muscle mass, bone density, or other aspects of nutritional status are reviewed. Specific recommendations for macronutrient intake, in particular protein, and selected micronutrients, vitamin D and B-12, as well as dietary fiber, and fluid intake as part of a hypocaloric diet and recommendations for physical activity are described. As part of the health professionals team, dietetics practitioners need to be able to guide and manage weight loss treatment options on an individual basis by evaluating the potential benefits against the potential risks in obese older adults.

Background: In older adults, studies demonstrate an inverse relationship between physical function and individual inflammatory biomarkers. Given that the inflammatory response is a complex system, a combination of biomarkers may increase the strength and consistency of these associations. This study uses principal component analysis to identify inflammatory "component(s)" and evaluates associations between the identified component(s) and measures of physical function., Methods: Principal component analysis with a varimax rotation was used to identify two components from eight inflammatory biomarkers measured in 1,269 older persons. The study sample is a subset of the Health, Aging, and Body Composition study., Results: The two components explained 56% of the total variance in the data (34%, component 1 and 22%, component 2). Five markers (tumor necrosis factor-alpha [TNF-alpha], sTNFRI, sTNFRII, interleukin [IL]-6sR, IL-2sR) loaded highest on the first component (TNF-alpha related), whereas three markers (C-reactive protein [CRP], IL-6, plasminogen activator inhibitor-1) loaded highest on the second component (CRP related). After adjusting for age, sex, race, site, sampling indicator, total lean and fat mass, physical activity, smoking, and anti-inflammatory drug use, knee strength and a physical performance battery score were inversely related to the TNF-alpha-related component, but not to the CRP-related component (knee strength: betaTNFalpha = -2.71, p = .002; betaCRP = -0.88, p = .325; physical performance battery score: betaTNFalpha = -0.05, p < .001; betaCRP = -0.02, p = .171). Both components were positively associated with 400-m walk time, inversely associated with grip strength, and not associated with 20-m walking speed., Conclusions: At least two inflammatory components can be identified in an older population, and these components have inconsistent associations with different aspects of physical performance.

Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovascular disease. Oxidized low-density lipoprotein (ox-LDL), a key player in the pathogenesis of atherosclerosis, may also play a role in arterial stiffening, but this relationship has not been well studied. Thus, we examined the cross-sectional association between ox-LDL and aortic pulse wave velocity (aPWV), a marker of arterial stiffness, in community-dwelling older adults. Plasma ox-LDL levels and aPWV were measured in 2295 participants (mean age: 74 years; 52% female; 40% black) from the Health, Aging, and Body Composition Study. Mean aPWV significantly increased across tertiles of ox-LDL (tertile 1: 869+/-376 cm/s; tertile 2: 901+/-394 cm/s; tertile 3: 938+/-415 cm/s; P=0.002). In multivariate analyses, ox-LDL remained associated with aPWV after adjustment for demographics and traditional cardiovascular disease risk factors (P=0.008). After further adjustment for hemoglobin A1c, abdominal visceral fat, antihypertensive and antilipemic medications, and C-reactive protein, the association with ox-LDL was attenuated but remained significant (P=0.01). Results were similar when ox-LDL was expressed in absolute (milligrams per deciliter) or relative amounts (percentage of low-density lipoprotein). Moreover, individuals in the highest ox-LDL tertile were 30% to 55% more likely to have high arterial stiffness, defined as aPWV >75th percentile (P

Obesity in middle and old age predicts mobility limitation; however, the cumulative effect of overweight and/or obesity over the adult life course is unknown. The association between overweight and/or obesity in young, middle, and late adulthood and its cumulative effect on incident mobility limitation was examined among community-dwelling US adults aged 70-79 years at baseline (1997-1998) in the Health, Aging and Body Composition Study (n = 2,845). Body mass index was calculated by using recalled weight at ages 25 and 50 years and measured weight at ages 70-79 years. Mobility limitation (difficulty walking 1/4 mile (0.4 km) or climbing 10 steps) was assessed semiannually over 7 years of follow-up and was reported by 43.0% of men and 53.7% of women. Men and women who were overweight or obese at all 3 time points had an increased risk of mobility limitation (hazard ratio = 1.61, 95% confidence interval: 1.25, 2.06 and hazard ratio = 2.85, 95% confidence interval: 2.15, 3.78, respectively) compared with those who were normal weight throughout. Furthermore, there was a significant graded response (P < 0.0001) on risk of mobility limitation for the cumulative effect of obesity in men and overweight and/or obesity in women. Onset of overweight and obesity in earlier life contributes to an increased risk of mobility limitation in old age.

Background: Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status., Methods: We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands); inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP); and anthropometric measures., Results: Higher levels of CRP and IL-6, but not TNF-alpha, were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results., Conclusions: Elevated CRP and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions.

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 consequences 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 > or =3 of the following: (a) waist circumference >102 (men) or >88 cm (women); (b) triglycerides > or =150 mg/dL; (c) high-density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women); (d) blood pressure > or =130/85 mm Hg or antihypertensive medication; and (d) fasting glucose > or =110 mg/dL or antidiabetic medication. Mobility limitation was defined as difficulty or inability walking (1/4) 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% CI = 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.

Background: Dietary surveys suggest that many older, community-dwelling adults consume insufficient dietary protein, which may contribute to the age-related loss of lean mass (LM)., Objective: The objective of the study was to determine the association between dietary protein and changes in total LM and nonbone appendicular LM (aLM) in older, community-dwelling men and women., Design: Dietary protein intake was assessed by using an interviewer-administered 108-item food-frequency questionnaire in men and women aged 70-79 y who were participating in the Health, Aging, and Body Composition study (n=2066). Changes in LM and aLM over 3 y were measured by using dual-energy X-ray absorptiometry. The association between protein intake and 3-y changes in LM and aLM was examined by using multiple linear regression analysis adjusted for potential confounders., Results: After adjustment for potential confounders, energy-adjusted protein intake was associated with 3-y changes in LM [beta (SE): 8.76 (3.00), P=0.004] and aLM [beta (SE): 5.31 (1.64), P=0.001]. Participants in the highest quintile of protein intake lost approximately 40% less LM and aLM than did those in the lowest quintile of protein intake (x+/-SE: -0.501+/-0.106 kg compared with -0.883+/-0.104 kg for LM; -0.400+/-0.058 kg compared with -0.661+/-0.057 kg for aLM; P for trend<0.01). The associations were attenuated slightly after adjustment for change in fat mass, but the results remained significant., Conclusion: Dietary protein may be a modifiable risk factor for sarcopenia in older adults and should be studied further to determine its effects on preserving LM in this population.

Background: The effect of the recent obesity epidemic on body composition remains unknown. Furthermore, age-related changes in body composition are still unclear., Objective: The objective was to simultaneously examine the effects of birth cohort and age on body composition., Design: A total of 1786 well-functioning, community-based whites and blacks (52% women and 35% blacks) aged 70-79 y from the Health, Aging, and Body Composition Study underwent dual-energy X-ray absorptiometry annually from 1997 to 2003., Results: At baseline, mean +/- SD percentage body fat, fat mass, and lean mass (bone-free) were 28 +/- 5%, 24 +/- 7 kg, and 56 +/- 7 kg, respectively, for men and 39 +/- 6%, 28 +/- 9 kg, and 40 +/- 6 kg for women. Mixed models were used to assess the effects of cohort and age-related changes on body composition. Later cohorts in men had a greater percentage body fat (0.32% per birth year, P < 0.0001) than did earlier cohorts. This cohort effect was due to a greater increase in fat mass than in lean mass (0.45 kg and 0.17 kg/birth year, respectively). With increasing age, percentage body fat in men initially increased and then leveled off. This age-related change was due to an accelerated decrease in lean mass and an initial increase and a later decrease in fat mass. Similar but less extreme effects of cohort and age were observed in women., Conclusions: The combination of effects of both birth cohort and age leads to bigger body size and less lean mass in the elderly.

Background: Oxidative damage plays an important role in leading to major health-related events. The aim of this study was to assess the predictive value of a lipoprotein peroxidation marker, oxidized low-density lipoprotein (oxLDL) for incident mobility limitation (ML)., Methods: Data are from 2985 well-functioning elders enrolled in the Health ABC study (median follow-up, 4.1 years). All oxLDL levels were measured at the baseline assessment. The oxLDL/LDL cholesterol (LDL-C) ratio (log value) was used as a measure of lipoprotein peroxidation. Mobility limitation was defined by 2 consecutive semiannual reports of any difficulty either walking 1/4 mile or climbing up 10 steps without resting. Severe ML was defined by 2 consecutive reports of great difficulty or inability to do the same tasks. Cox proportional hazards models were performed to assess hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: The mean (SD) age of the sample was 74.2 (2.9) years. After adjustment for potential confounders (sociodemographic factors, smoking, physical activity, body mass index, clinical conditions, biological markers, and medications), the relationship between the oxLDL/LDL-C ratio and disability events was statistically significant (per log-unit difference in the oxLDL/LDL-C ratio) (for ML: HR, 1.22; 95% CI, 1.06-1.41; for severe ML: HR, 1.43; 95% CI, 1.15-1.79). Consistent results were found when interleukin 6 level was included as a covariate in the adjusted models (ML: HR, 1.13; 95% CI, 0.98-1.31; severe ML: HR, 1.31; 95% CI, 1.05-1.64). No significant sex, race, interleukin 6 level, or clinical conditions interaction was found with the oxLDL/LDL-C ratio and mobility disability., Conclusions: Lipoprotein peroxidation predicts the onset of ML in older persons. The oxLDL predictive value for ML is partly explained by interleukin 6 levels.

Objectives: To define clinically relevant cutpoints for usual gait speed and to investigate their predictive value for health-related events in older persons., Design: Prospective cohort study., Setting: Health, Aging and Body Composition Study., Participants: Three thousand forty-seven well-functioning older persons (mean age 74.2)., Measurements: Usual gait speed on a 6-m course was assessed at baseline. Participants were randomly divided into two groups to identify (Sample A; n=2,031) and then validate (Sample B; n=1,016) usual gait-speed cutpoints. Rates of persistent lower extremity limitation events (mean follow-up 4.9 years) were calculated according to gait speed in Sample A. A cutpoint (defining high- (< 1 m/s) and low risk (> or = 1 m/s) groups) was identified based on persistent lower extremity limitation events. The predictive value of the identified cutpoints for major health-related events (persistent severe lower extremity limitation, death, and hospitalization) was evaluated in Sample B using Cox regression analyses., Results: A graded response was seen between risk groups and health-related outcomes. Participants in the high-risk group had a higher risk of persistent lower extremity limitation (rate ratio (RR)=2.20, 95% confidence interval (CI)=1.76-2.74), persistent severe lower extremity limitation (RR=2.29, 95% CI=1.63-3.20), death (RR=1.64, 95% CI=1.14-2.37), and hospitalization (RR=1.48, 95% CI=1.02-2.13) than those in the low-risk group., Conclusion: Usual gait speed of less than 1 m/s identifies persons at high risk of health-related outcomes in well-functioning older people. Provision of a clinically meaningful cutpoint for usual gait speed may facilitate its use in clinical and research settings.

BackgroundMitochondrial function declines with age; however, the relationship between adiposity and mitochondrial function among older adults is unclear. This study examined relationships between skeletal muscle mitochondrial content and electron transport chain complex 2 driven respiration with whole body and thigh composition, body fat distribution, and insulin sensitivity in older adults.Methods25 healthy, sedentary, weight-stable men (N = 13) and women (N = 12) >65 years of age, with a BMI range of 18-35 kg/m(2), participated in this study. Vastus lateralis biopsies were analyzed for citrate synthase (CS) activity and succinate mediated respiration of isolated mitochondria. Whole body and thigh composition were measured by DXA and CT. HOMA-IR was calculated using fasting glucose and insulin as an estimate of insulin sensitivity.ResultsSimilar to reports in middle-aged adults, skeletal muscle CS activity was negatively correlated with BMI (R = -0.43) in our cohort of older adults. Higher total and thigh adiposity were correlated with lower CS activity independent of BMI (R = -0.50 and -0.71 respectively). Maximal complex 2 driven mitochondrial respiration was negatively correlated with lower body adiposity in males (R = -0.66). In this cohort of non-diabetic older adults, both HOMA-IR and insulin were positively correlated with CS activity when controlling for BMI (R = 0.57 and 0.66 respectively).ConclusionsAdiposity and body composition are correlated with skeletal muscle mitochondrial content and electron transport chain function in healthy, sedentary, community dwelling, older adults. Specific relationships of mitochondrial bioenergetics with gender and insulin sensitivity are also apparent.Trial registrationClinicalTrials.gov identifier NCT01049698.

Background: Cardiopulmonary exercise testing (CPET), the gold‐standard method to quantify cardiorespiratory fitness (CRF), is not always feasible due to cost, access, and burden. The usual‐paced 400 m long distance corridor walk (LDCW), a measure of mobility among older adults, may provide an alternate method to assess CRF. The purpose of this study was to develop and validate an estimating equation to estimate VO2peak from average 400 m walking speed (WS) among participants in the Study of Muscle, Mobility and Aging (SOMMA). Methods: At baseline, women (58%) and men age 70 years and older enrolled in SOMMA (N = 820, 76.2 ± 4.9 years, 86% Non‐Hispanic White) completed a 400 m LDCW (400 m WS = 400 m/completion time in seconds) and symptom‐limited maximal CPET (Modified Balke Protocol). VO2peak (mL/kg/min) was considered the highest 30‐second average oxygen consumption during CPET. Other covariates included: age, sex, race, physical activity (7‐day wrist‐worn accelerometer), physical function (Short Physical Performance Battery, range 0–12), perceived physical fatigability (Pittsburgh Fatigability Scale, range 0–50), and Borg Rating of Perceived Exertion (RPE, range 6–20) at completion of the 400 m LDCW. Stepwise linear regression was used. Internal validation was completed using data‐splitting method (70%; 30%). Results: Mean VO2peak was 20.2 ± 4.8 mL/kg/min and mean 400 m WS was 1.06 ± 0.2 m/s. Each 0.05 m/s increment in 400 m WS was associated with a 0.40 mL/kg/min higher VO2peak after covariate adjustment. An estimating equation including 400 m WS, age, sex, race, and RPE was developed. Internal validation showed low overall bias (−0.26) and strong correlation (r = 0.71) between predicted and measured VO2peak values. Bland–Altman plot and regression analyses indicated predicted VO2peak was an acceptable alternative, despite mean underestimation of 4.53 mL/kg/min among the highly fit. Conclusions: Usual‐paced 400 m LDCW strongly correlates with direct measures of CRF during CPET in older adults with lower fitness and can be used to test both fitness and function. [ABSTRACT FROM AUTHOR]

Cellular senescence is a biological aging process that is exacerbated by obesity and leads to inflammation and age- and obesogenic-driven chronic diseases including type 2 diabetes. Caloric restriction (CR) may improve metabolic function in part by reducing cellular senescence and the pro-inflammatory senescence-associated phenotype (SASP). We conducted an ancillary investigation of an 18-week randomized controlled trial (RCT) of CR (n  = 31) or Control (n  = 27) in 58 middle-aged/older adults (57.6 ± 5.8 years; 75% Women) with obesity and prediabetes. We measured mRNA expression of select senescence and apoptosis genes in blood CD3 + T cells (qRT-PCR) and a panel of 25 plasma SASP proteins (Luminex/multiplex; ELISA). Participants randomized to CR lost −10.8 ± 0.9 kg (−11.3% ± 5.4%) over 18 weeks compared with +0.5 ± 0.9 kg (+0.03% ± 3.5%) in Control group. T-cell expression of senescence biomarkers, p16INK4a and p21CIP1/WAF1, and apoptosis markers, BCL2L1 and BAK1, was not different between CR and Control groups in age, race, and sex-adjusted mixed models (p  > .05, all). Iterative principal axis factor analysis was used to develop composite SASP Factors, and the Factors comprising TNFRI, TNFRII, uPAR, MMP1, GDF15, OPN, Fas, and MPO were significantly altered with CR intervention (age, sex, race-adjusted mixed model time × treatment F  = 4.17, p  ≤ .05) and associated with the degree of weight loss (R 2 = 0.12, p  ≤ .05). Our study provides evidence from an RCT that specific circulating biomarkers of senescent cell burden are changed by CR in middle-aged and older adults with obesity and prediabetes. Future studies compare tissue and circulating levels of p16INK4a and pro-inflammatory SASP biomarkers in other populations, and interventions. [ABSTRACT FROM AUTHOR]

Observational studies show a relationship between elevated serum uric acid (UA) and better physical performance and muscle function. The purpose of this paper was to determine whether regular participation in an exercise intervention, known to improve physical functioning, would result in increased serum UA. For this study, 424 older adults at risk for physical disability were randomized to participate in either a 12-mo moderate-intensity physical activity (PA) or a successful aging (SA) health education intervention. UA was measured at baseline, 6, and 12 mo (n = 368, 341, and 332, respectively). Baseline UA levels were 6.03 ± 1.52 mg/dl and 5.94 ± 1.55 mg/dl in the PA and SA groups, respectively. The adjusted mean UA at month 12 was 4.8% (0.24 mg/dl) higher in the PA compared with the SA group (p = .028). Compared with a health education intervention, a 1-yr PA intervention results in a modest increase in systemic concentration of UA in older adults at risk for mobility disability. [ABSTRACT FROM AUTHOR]

Background: Adiposity-related ventilatory constraints in older adults can potentially contribute to greater risk of exercise intolerance and mobility disability. This study investigated whether ventilatory limitation, measured by breathing reserve (BR) at peak exercise, is associated with body composition and physical function in older adults with obesity.Methods: This study was a cross-sectional analysis of data from a community-based cohort (N = 177) of older men and women (65-79 years) with obesity (body mass index = 30-45 kg/m2). All participants underwent cardiopulmonary exercise testing on a treadmill, dual-energy X-ray absorptiometry for body composition, and physical function assessments. We examined relationships between BR and body composition and physical function using multiple linear regression and compared a subset with (BR ≤ 30%; BR-low; n = 56) and without (BR ≥ 45%; BR-high, n = 48) ventilatory limitation using unpaired Student's t test and analysis of covariance.Results: BR was inversely related to total body mass, lean mass, fat mass, % body fat, and waist circumference (p < 0.05 for all). BR was positively related to 400 m walk time (p = .006) and inversely related to usual gait speed (p = .05) and VO2peak (p < .0001), indicative of worse physical function. BR-low had greater adiposity, but also greater lean mass, higher VO2peak, and faster 400 m walk time, compared to BR-high (p < .05, for all).Conclusions: Older adults with obesity who also have ventilatory limitation have overall higher measures of adiposity, but do not have lower peak exercise capacity or physical function. Thus, ventilatory limitation does not appear to be a contributing factor to obesity-related decrements in exercise tolerance or mobility. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study aims to investigate the impact of respiratory symptoms in current and former smokers with and without obstructive lung disease (OLD) on all‐cause mortality. DESIGN: Secondary analysis in a prospective cohort (the Health, Aging and Body Composition study). SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Black and white men and women with a history of current and former smoking (N = 596; 63% male and 37% female) aged 70‐79 years followed for 13 years. Participants were categorized into 4 mutually exclusive groups based on symptom profile and forced expiratory volume in the 1st second to forced vital capacity ratio. The groups were Less Dyspnea‐No OLD (N = 196), More Dyspnea‐No OLD (N = 104), Less Dyspnea‐With OLD (N = 162), and More Dyspnea‐With OLD (N = 134). MEASUREMENTS: All‐cause mortality. RESULTS: Overall, 53% in Less Dyspnea‐No OLD, 63% in More Dyspnea‐No OLD, 67% in Less Dyspnea‐With OLD, and 84% in More Dyspnea‐With OLD died within the 13‐ year follow up period (log‐rank χ2 = 44.4, P < .0001). The hazard ratio was highest for participants with OLD, both with (HR =1.91, 95% CI 1.44 ‐ 2.54; P < .0001) and without dyspnea (HR = 1.52, 95% CI 1.15 ‐ 2.02; p = .004). Participants without OLD but with dyspnea had a similar risk of death to subjects who had OLD but fewer symptoms. CONCLUSIONS: OLD is associated with high risk of death with different risk profiles based on symptom group. Patients with symptoms of shortness of breath without OLD should be considered an at‐risk group given their similar mortality to those with OLD with minimal symptoms. J Am Geriatr Soc 67:2116–2122, 2019 [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the ability of either aerobic or resistance training to counter weight‐loss‐associated bone loss in older adults. There were 187 older adults (67 years, 70% women, 64% white) with obesity (BMI = 34.5 ± 3.7 kg/m2) and cardiovascular disease and/or metabolic syndrome who were randomized to participate in an 18‐month, community‐based trial, with a follow‐up assessment at 30 months. Intervention arms included: weight loss alone (WL; 7% to 10% baseline weight), WL plus aerobic training (WL + AT), and WL plus resistance training (WL + RT), as well as DXA‐acquired total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD), and trabecular bone score (TBS). Biomarkers of bone turnover (procollagen type 1 N‐terminal propeptide, C‐terminal telopeptide of type 1 collagen) were measured at baseline, 6, 18, and 30 (aBMD and TBS only) months. CT‐acquired hip and spine volumetric BMD (vBMD), cortical thickness, and bone strength were measured in a subset at baseline (n = 55) and 18 months. Total hip aBMD was reduced by 2% in all groups at 18 months, with a primary analysis showing no significant treatment effects for any DXA, biomarker, or CT outcome. After adjustment for WL and follow‐up at 30 months, secondary analyses revealed that total hip [−0.018 (−0.023 to −0.012) g/cm2 versus −0.025 (−0.031 to −0.019) g/cm2; p = 0.05] and femoral neck [−0.01 (−0.009 to 0.008) g/cm2 versus −0.011 (−0.020 to −0.002) g/cm2; p = 0.06] aBMD estimates were modestly attenuated in the WL + RT group compared with the WL group. Additionally, lumbar spine aBMD was increased in the WL [0.015 (0.007 to 0.024) g/cm2] and the WL + RT [0.009 (0.000 to 0.017) g/cm2] groups compared with the WL + AT [−0.003 (−0.012 to 0.005)g/cm2] group; both p ≤ 0.01. Community‐based exercise does not prevent bone loss during active WL in older adults; however, adding RT may help minimize long‐term hip bone loss. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

BACKGROUND Arterial stiffness is an important marker of vascular aging that is increased in sedentary, obese older adults. Weight loss induced by caloric restriction (CR) can improve arterial stiffness in this population; however, the effects of resistance training (RT) are not clear. This pilot study determined the effects of RT with and without CR on arterial stiffness in overweight and obese older adults. METHODS Participants (mean age = 68 ± 3 years, mean body mass index = 31.1 ± 2.7 kg/ m2, 56% female, 13% Black) were randomly assigned to 3 days/week of supervised moderate-intensity RT (n = 16) or RT+CR (n = 16) for 5 months. Three indices of arterial stiffness were measured: brachial-ankle pulse wave velocity, large artery elasticity, and small artery elasticity. RESULTS Body mass was significantly reduced in the RT+CR group compared to the RT group (-6.2 ± 4.8 vs. 0.2 ± 1.2 kg, P = 0.0006). Within-group analyses showed that none of the arterial stiffness measures changed with RT or RT+CR. There were also no significant between-group differences, though median changes in large artery elasticity were slightly greater with RT+CR: 0.7 (-2.5, 5.1) vs. 0.3 (-2.6, 0.9) ml/mm Hg × 10, P = 0.07. Changes in large artery elasticity were negatively correlated with changes in waist circumference (r = -0.36, P < 0.05), systolic blood pressure (r = -0.38, P = 0.03), and diastolic blood pressure (r = -0.41, P = 0.02). CONCLUSIONS The combination of RT and CR, leading to a modest amount of weight loss (7%), tended to increase large artery elasticity more than RT alone. Our data suggest that reductions in waist circumference and blood pressure may promote improvements in elasticity. [ABSTRACT FROM AUTHOR]

To date, physical exercise is the only intervention consistently demonstrated to attenuate age-related declines in physical function. However, variability exists in seniors' responsiveness to training. One potential source of variability is the insertion (I allele) or deletion (D allele) of a 287 bp fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene. This polymorphism is known to influence a variety of physiological adaptions to exercise. However, evidence is inconclusive regarding the influence of this polymorphism on older adults' functional responses to exercise. This study aimed to evaluate the association of ACE I/D genotypes with changes in physical function among Caucasian older adults (n = 283) following 12 mo of either structured, multimodal physical activity or health education. Measures of physical function included usual-paced gait speed and performance on the Short Physical Performance Battery (SPPB). After checking Hardy-Weinberg equilibrium, we used using linear regression to evaluate the genotype*treatment interaction for each outcome. Covariates included clinic site, body mass index, age, sex, baseline score, comorbidity, and use of angiotensin receptor blockers or ACE inhibitors. Genotype frequencies [II (19.4%), ID (42.4%), DD (38.2%)] were in Hardy-Weinberg equilibrium (P > 0.05). The genotype*treatment interaction was statistically significant for both gait speed (P = 0.002) and SPPB (P = 0.020). Exercise improved gait speed by 0.06 ± 0.01 m/sec and SPPB score by 0.72 ± 0.16 points among those with at least one D allele (ID/DD carriers), but function was not improved among II carriers. Thus, ACE I/D genotype appears to play a role in modulating functional responses to exercise training in seniors. [ABSTRACT FROM AUTHOR]

Objectives To determine the independent effect of long-term physical activity ( PA) and the combined effects of long-term PA and weight loss ( WL) on inflammation in overweight and obese older adults. Design Eighteen-month randomized, controlled trial. Setting The community infrastructure of cooperative extension centers. Participants Overweight and obese (body mass index >28.0 kg/m2) community-dwelling men and women aged 60 to 79 at risk for cardiovascular disease ( CVD). Intervention Physical activity + weight loss (PA + WL) (n = 98), PA only (n = 97), or successful aging ( SA) health education (n = 93) intervention. Measurements Biomarkers of inflammation (adiponectin, leptin, high-sensitivity interleukin (hs IL)-6, IL-6s R, IL-8, and soluble tumor necrosis factor receptor 1) were measured at baseline and 6 and 18 months. Results After adjustment for baseline biomarker, wave, sex, and visit, leptin and hsIL-6 showed a significant intervention effect. Specifically, leptin was significantly lower in the PA + WL group (21.3 ng/mL, 95% confidence interval ( CI) = 19.7-22.9 ng/mL) than in the PA (29.3 ng/mL, 95% CI = 26.9-31.8 ng/mL) or SA (30.3 ng/mL, 95% CI = 27.9-32.8 ng/mL) group (both P < .001), and hs IL-6 was significantly lower in the PA + WL group (2.1 pg/mL, 95% CI = 1.9-2.3 pg/mL) than in the PA (2.5 pg/mL, 95% CI = 2.3-2.7 pg/mL) or SA (2.4 pg/mL, 95% CI = 2.2-2.6 pg/mL) group ( P = .02). Conclusion Addition of dietary-induced WL to PA reduced leptin and hs IL-6 more than PA alone and more than a SA intervention in older adults at risk for CVD. Results suggest that WL, rather than increased PA, is the lifestyle factor primarily responsible for improvement in the inflammatory profile. [ABSTRACT FROM AUTHOR]

Background. Vitamin D deficiency is common among older adults and is associated with poor physical performance; however, studies examining longitudinal changes in 25-hydroxyvitamin D (25[OH]D) and physical performance are lacking. We examined the association between 25(OH)D and physical performance over 12 months in older adults participating in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P), a multicenter physical activity intervention trial. Methods. Plasma 25(OH)D and physical performance, assessed by the short physical performance battery (SPPB) and 400-m walk test, were measured at baseline, 6-month, and 12-month follow-up in community-dwelling adults aged 70–89 years at risk for disability (n = 368). Mixed models were used to examine the association between 25(OH)D and physical performance adjusting for demographics, intervention group, season, body mass index, and physical activity. Results. One half of the participants were vitamin D deficient (25[OH]D < 20 ng/mL) at baseline. In cross-sectional analyses, vitamin D deficiency was associated with lower SPPB scores and slower 400-m walk speeds (mean difference [SE]: 0.35 [0.16], p = .03 and 0.04 [0.02] m/s, p = .01, respectively). Although baseline 25(OH)D status was not significantly associated with change in physical performance over 12 months, individuals who were vitamin D deficient at baseline but no longer deficient at follow-up had significant improvements in SPPB scores (mean difference [SE]: 0.55 [0.22], p = .01) compared with those whose 25(OH)D status remained the same. Conclusion. Increases in 25(OH)D to greater than or equal to 20 ng/mL were associated with clinically significant improvements in physical performance among older adults. [ABSTRACT FROM PUBLISHER]

Background.: Although weight loss reduces risk for comorbid diseases, many observational studies suggest that weight loss is associated with increased mortality risk, leading to reluctance by clinicians to consider weight reduction as a strategy to maintain health and independence in older adults. However, whether the observed weight loss is intentional is difficult to determine and may not accurately represent the mortality risk associated with intentional weight reduction. Data from the Arthritis, Diet, and Activity Promotion Trial (ADAPT) were used to determine whether randomization to a weight reduction program was associated with total mortality in overweight/obese older adults. Methods. ADAPT (n = 318; mean age 69 ± 6 years, body mass index 34 ± 5 kg/m2,72% female) assessed the influence of weight loss (achieved through dietary counseling and lifestyle modification) and/or exercise on function in overweight/ obese older adults with knee osteoarthritis. ADAPT ended in December 1999. Participant vital was ascertained status through December 2006 using the National Death and Social Security Indexes. Results. The mortality rate for those randomized to the 18-month weight loss intervention (n = 159, mean weight loss = -4.8 kg, 15 deaths) was lower than that for those not randomized to the weight loss intervention (n = 159, mean weight loss = -1.4 kg, 30 deaths; hazard rate ratio = 0.5,95% confidence interval 0.3-1.0). Results were not appreciably changed when analyses were stratified by age, gender, baseline weight status, or magnitude of weight loss. Conclusions. In older adults, intentional weight loss was not associated with increased total mortality and may reduce mortality risk. Observational studies of weight loss, especially when intentionality cannot be rigorously established, may be misleading with respect to the effect of weight loss on mortality. [ABSTRACT FROM PUBLISHER]

The article offers information on several studies examining exercise as a treatment for chronic inflammation in elderly. According to research, physical activity serves to reduce low-grade inflammation, which is an important contributor to the pathophysiology of some chronic health conditions, such as disability. Information regarding C reactive protein (CRP) and tumor necrosis factor (TNF) in inflammation is provided.

Background. In older adults, studies demonstrate an inverse relationship between physical function and individual inflammatory biomarkers. Given that the inflammatory response is a complex system, a combination of biomarkers may increase the strength and consistency of these associations. This study uses principal component analysis to identify inflammatory "component(s)" and evaluates associations between the identified component(s) and measures of physical function. Methods. Principal component analysis with a varimax rotation was used to identify two components from eight inflammatory biomarkers measured in 1,269 older persons. The study sample is a subset of the Health, Aging, and Body Composition study. Results. The two components explained 56% of the total variance in the data (34%, component I and 22%, component 2). Five markers (tumor necrosis factor-alpha [TNF-α], sTNFRI, sTNFRII, interleukin [IL]-6sR, lL-2sR) loaded highest on the first component (TNF-α related), whereas three markers (C-reactive protein [CRP], lL-6, plasminogen activator inhibitor-I) loaded highest on the second component (CRP related). After adjusting for age, sex, race, site, sampling indicator, total lean and fat mass, physical activity, smoking, and anti-inflammatory drug use, knee strength and a physical performance battery score were inversely related to the TNF-α-related component, but not to the CRP-related component (knee strength: βˆTNFα = -2.71, p = .002; βˆCRP = -0.88, p = .325; physical performance battery score: βˆTNFα = -0.05, p <.001; βˆCRP = -0.02,p = .171). Both components were positively associated with 400-m walk time, inversely associated with grip strength, and not associated with 20-m walking speed. Conclusions. At least two inflammatory components can be identified in an older population, and these components have inconsistent associations with different aspects of physical performance. [ABSTRACT FROM AUTHOR]

Participating in sufficient levels of physical activity is important for sustaining health and quality of life across the age span. The United States Physical Activity Guidelines recommend individuals of all ages "move more, more often" by frequently engaging in aerobic activity while avoiding prolonged bouts of sitting. This is indicative of a slow shift in focus in the study of active aging that has occurred in the last two decades. Historically, researchers interested in the influence of physical activity on older adults' health and quality of life focused on discrete sustained bouts of intense activity (i.e., structured exercise). More recently the widespread usage of accelerometers contributed to a large body of evidence demonstrating that long periods spent sedentary were associated with a host of negative health outcomes ranging from poorer cardiometabolic health to poorer physical functioning and elevated risk of death. These findings often persisted when controlling for time spent in higher-intensity physical activity, spurring separate fields of intervention research concerned with promoting exercise or reducing sedentary time. Novel data emerging in recent years on the importance of an individual's overall activity profile (i.e., amount and patterning of light and moderate-to-vigorous activity) has driven yet another shift in focus toward interventions focused explicitly on movement profiles. In this narrative review, we discuss the evolution of thought regarding older adults' physical activity behaviors. We highlight successes and challenges in first promoting structured and prolonged exercise, later in targeting sedentary behavior, and most recently in attempting to intervene on activity profiles. We end our review by highlighting current gaps in research and important future directions. • Physical activity is an important behavioral medicine to individuals of all ages. • Early research focused on purposeful, sustained exercise with little success in promoting lasting exercise behavior change. • Sedentary behavior was more recently identified as a health threat, but few long-term interventions exist. • Promoting the accumulation of daily movement represents new frontier for physical activity programming for older adults. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the effects of a long-term exercise intervention on two prominent biomarkers of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in elderly men and women. DESIGN: Single-blind, randomized, controlled trial: The Lifestyle Interventions and Independence for Elders (LIFE) Trial. SETTING: The Cooper Institute, Dallas, Texas; Stanford University, Stanford, California; University of Pittsburgh, Pittsburgh, Pennsylvania; and Wake Forest University, Winston-Salem, North Carolina. PARTICIPANTS: Four hundred twenty-four elderly (aged 70–89), nondisabled, community-dwelling men and women at risk for physical disability. INTERVENTION: A 12-month moderate-intensity physical activity (PA) intervention and a successful aging (SA) health education intervention. MEASUREMENTS: CRP and IL-6. RESULTS: After adjustment for baseline IL-6, sex, clinic site, diabetes mellitus, treatment group, visit, and group-by-visit interaction, the PA intervention resulted in a lower ( P=.02) IL-6 concentration than the SA intervention. Adjusted mean IL-6 at month 12 was 8.5% (0.21 pg/mL) higher in the SA than the PA group. There were no significant differences in CRP between the groups at 12 months ( P=.09). Marginally significant interaction effects of the PA intervention according to baseline functional status ( P=.05) and IL-6 (above vs below the median; P=.06) were observed. There was a greater effect of the PA intervention on participants with lower functional status and those with a higher baseline IL-6. CONCLUSION: Greater PA results in lower systemic concentrations of IL-6 in elderly individuals, and this benefit is most pronounced in individuals at the greatest risk for disability and subsequent loss of independence. [ABSTRACT FROM AUTHOR]

Controversy exists as to whether there are differences in insulin action between older men and women, and what factors contribute to these differences. This study tests the hypothesis that sex differences in regional fat distribution contribute to a disparity in insulin sensitivity in older men vs. older women. Healthy, older (50-71 years), sedentary men (n = 28) and women (n = 29) were recruited to participate in the study. Body fat, fat-free mass (FFM), and visceral (VAT) and subcutaneous abdominal (SAT) adipose tissue areas were measured by DXA and computed tomography (CT). For measurements of insulin-stimulated glucose disposal (M), insulin was infused at a constant rate of 240 pmol·m-2·min-1, and M was calculated between the 90th and 120th min of the hyperinsulinemic-euglycemic clamp. The men weighed 16% more and had 16% higher waist and 4% lower hip circumferences than women (p < 0.05 for all). Total fat mass and SAT were 21% and 33% lower and FFM was 49% higher in men than in women, whereas waist-to-hip ratio (WHR) and VAT:SAT ratio were 21% and 56% higher in men than in women (p < 0.05 for all). Although insulin concentrations during the glucose clamp were higher in men, M was 47% lower in men vs. women (21.7 ± 1.1 vs. 46.7 ± 3.1 µmol·L-1·kgFFM-1·min-1, p < 0.05). The sex-related differences in M persisted after controlling for insulin concentrations during the glucose clamp, for waist, WHR, and VAT:SAT. Older men are more insulin resistant than women, despite lower body fat and subcutaneous abdominal fat. This difference in insulin sensitivity is not explained by abdominal fat distribution, therefore other metabolic factors contribute to the sex differences in insulin sensitivity. On ne sait toujours pas si l’action de l’insuline diffère entre une femme âgée et un homme âgé et quels en sont les facteurs. Cette étude teste l’hypothèse selon laquelle les différences sexuelles de distribution de la graisse dans l’organisme contribuent aux différences de sensibilité à l’insuline entre les personnes âgées des deux sexes. Vingt-neuf femmes et vingt-huit hommes âgés de 50 à 71 ans, sédentaires et en bonne santé, participent à cette étude. On évalue par absorptiométrie biénergétique à rayons-X (DXA) et tomodensitométrie (CT) le contenu corporel de graisses, la masse maigre (FFM), les contenus viscéral (VAT) et sous-cutané dans la région abdominale (SAT) de tissu adipeux. Pour la mesure de la captation du glucose médiée par l’insuline (M), on infuse l’insuline à un taux constant de 240 pmol·m-2·min-1 et on évalue M entre la 90e et la 120e minute de la période du clamp euglycémique hyperinsulinémique. Comparativement aux femmes, les hommes ont une masse corporelle plus importante de 16 %, un tour de taille plus grand de 16 % et un tour de hanches plus petit de 4 % (p < 0,05 pour toutes les différences). Comparativement aux femmes, le contenu total de graisses et le SAT des hommes sont de 21 % et 33 % inférieurs respectivement et la FFM est de 49 % supérieure ; le ratio tour de taille / tour de hanches (WHR) et le ratio VAT:SAT sont de 21 % et 56 % supérieurs respectivement (p < 0,05 pour toutes les différences). Même si les hommes présentent une plus grande concentration d’insuline au cours de la période du clamp, M est de 47 % inférieure chez les hommes (21,7 ± 1,1 comparativement à 46,7 ± 3,1 µmol·L-1·kgFFM-1·min-1, p < 0,05). Les différences de M liées au sexe demeurent après la prise en compte des valeurs de concentration d’insuline au cours de la période du clamp et après la prise en compte du tour de taille, du WHR et du VAT:SAT. Les hommes âgés sont plus résistants à l’insuline, et ce, malgré une moindre grande quantité de graisses corporelles et de tissus adipeux sous-cutanés dans la région abdominale. La répartition des graisses abdominales n’explique pas la différence de sensibilité à l’insuline ; il y a donc d’autres facteurs métaboliques qui contribuent à cette différence liée au sexe. [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]