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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 AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: There are no data showing whether or not age-related declines in physical function are related to in vitro properties of human skeletal muscle. The purpose of this study was to determine whether physical function is independently associated with histologic and metabolic properties of skeletal muscle in elderly adults. METHODS: The study was a cross-sectional observational study of 39 sedentary, older (60-85 yrs) men and women. A needle biopsy of the vastus lateralis for assessment of muscle fiber type, fiber area, capillary density and citrate synthase and aldolase activities was performed. Physical function tests included the Short Physical Performance Battery (balance, walking speed, and chair rise time), as well as self-reported disability. RESULTS: Total fiber area (R=-0.41, p=0.02), number of Type II fibers (R=-0.33, p=0.05), and aldolase activity (R=-0.54, p=0.01) were inversely related to age. Persons who reported greater difficulty with daily activities had lower capillary density (R=-0.51, p=0.03) and lower citrate synthase activity (R=-0.66, p=0.03). Walking speed was directly related to fiber area (R=0.40, p=0.02), capillary density (R=0.39, p=0.03), citrate synthase (R=0.45, p=0.03) and aldolase (R=0.55, p<0.01) activities, even after adjustment for age, BMI and disease status. CONCLUSIONS: In older adults, skeletal muscle capillary density and metabolic enzymatic activity are independent predictors of lower extremity physical function. [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: 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. Copyright © 2007 American Society for Nutrition [ABSTRACT FROM AUTHOR]

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 (>/=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. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Adipose tissue distribution (visceral vs subcutaneous) has been shown to be an important predictor of insulin resistance, diabetes and cardiovascular disease, independent of body mass index. The beta-2 adrenergic receptor is a major lipolytic receptor in human fat cells and the gene that codes for this protein is an important candidate gene for measures of adiposity and fat deposition. We examined whether two common polymorphisms in codons 16 (Arg16Gly) and 27 (Gln27Glu) are associated with measures of fat distribution in participants of the IRAS Family Study. METHODS:: We recruited African-American (AA) and Hispanic-American (HA) families from Los Angeles, CA, USA (18 pedigrees, 272 AA individuals), San Antonio, TX, USA (33 pedigrees, 448 HA individuals) and San Luis Valley, CO, USA (12 pedigrees, 272 HA individuals). We estimated adipose tissue distribution via computed tomography. To test for an association between adiposity measures and these polymorphisms, we used generalized estimating equations, adjusting for age, gender, clinical site (ethnicity), body mass index, and familial correlation. RESULTS:: Of the 992 individuals genotyped for these polymorphisms, 57%were female and 15%had been diagnosed with type 2 diabetes mellitus. The mean age was 42.7±14.6?y. The Glu27 allele of the Gln27Glu polymorphism was positively associated with (P-value for recessive model): body mass index (0.025), visceral adipose tissue (<0.0001) and visceral-to-subcutaneous adipose ratio (0.009), but not with subcutaneous adipose tissue (0.952). The Arg16Gly polymorphism was not associated with any of the adiposity measures. CONCLUSIONS:: These findings suggest that genetic variation in the beta-2 adrenergic receptor gene influences fat deposition and body size in AAs and HAs. In particular, these results support a role for the gene in the distribution of visceral adipose tissue but not subcutaneous adipose tissue.International Journal of Obesity (2005) 29, 449-457. doi:10.1038/sj.ijo.0802883 Published online 18 January 2005 [ABSTRACT FROM AUTHOR]

Assessment of body fat distribution, particularly visceral adipose tissue, may be important for accurate risk evaluation for cardiovascular disease in the elderly. This 1997-1998 US study examined the association of incident myocardial infarction (MI) with total adiposity (body mass index and fat mass) and body fat distribution (waist-to-thigh ratio, waist circumference, visceral and subcutaneous adipose tissue) in well-functioning men (n = 1,116) and women (n = 1,387) aged 70-79 years enrolled in the Health, Aging and Body Composition Study. There were 116 MI events (71 in men, 45 in women) during an average follow-up time of 4.6 (standard deviation, 0.9) years. No association was found between incident MI and the adiposity or fat distribution variables for men. For women, visceral adipose tissue was an independent predictor of MI (hazard ratio = 1.67, 95% confidence interval: 1.28, 2.17 per standard-deviation increase; p < 0.001). No association was found between body mass index or total fat mass and MI events in women. The association of visceral adipose tissue with MI in women was independent of high density lipoprotein cholesterol, interleukin-6 concentration, hypertension, and diabetes (hazard ratio = 1.79, 95% confidence interval: 1.24, 2.58 per standard-deviation increase; p < 0.01). The amount of adipose tissue stored in the intraabdominal cavity is an important, independent risk factor for MI in well-functioning, elderly women. [ABSTRACT FROM AUTHOR]

Background: There are few empirical data to support the claim that weight loss improves coronary heart disease (CHD) risk factors in postmenopausal women; nor is it known if there are racial differences in changes of body fat distribution, lipids, glucose tolerance, and blood pressure with weight loss. This study determined the efficacy of a lifestyle weight loss intervention in reducing total and abdominal obesity and improving CHD risk factors in obese Caucasian and African-American postmenopausal women.Methods: Body composition (dual-energy x-ray absorptiometry), abdominal fat areas (computed tomography scan), lipoprotein lipids, insulin, glucose tolerance, and blood pressure were measured before and after 6 months of hypocaloric diet and low-intensity walking in 76 overweight or obese (body mass index > 25 kg/m(2)), Caucasian (72%) or African-American (28%), postmenopausal (age = 60 +/- 5 years) women who completed the study.Results: Absolute amount of body weight lost was similar in Caucasians (-5.4 +/- 3.6 kg) and African Americans (-3.9 +/- 3.6 kg), but Caucasian women lost relatively more fat mass (p <.05). Both groups decreased their subcutaneous abdominal fat, and Caucasian women decreased their visceral fat area, but there were no racial differences in the magnitude of abdominal fat lost. The intervention decreased triglyceride and increased high-density lipoprotein and high-density lipoprotein 2 cholesterol in both races, and it decreased total and low-density lipoprotein cholesterol in Caucasian women (p <.05-.0001). Fasting glucose and glucose area during the oral glucose tolerance test decreased (p <.0001) in Caucasian women, whereas insulin area decreased in both Caucasian (p <.01) and African-American (p <.05) women. Blood pressure decreased the most in women with higher blood pressures at baseline. Changes in lipids, fasting glucose and insulin, their responses during the oral glucose tolerance test, and blood pressure were not different between racial groups.Conclusions: Weight loss achieved through a lifestyle intervention of energy restriction and increased physical activity is an equally effective therapy in African-American and Caucasian obese, postmenopausal women for improving glucose and lipid CHD risk factors. [ABSTRACT FROM AUTHOR]

This study investigates the association of several inflammatory markers with subclinical and clinical cardiovascular disease in older men and women. Data are from the baseline assessment of 3,045 well-functioning persons aged 70 to 79 years, participating in the Health, Aging and Body Composition study. The study sample was divided into 3 groups: "cardiovascular disease" (diagnosis of congestive heart failure, coronary artery disease, peripheral artery disease, or stroke), "subclinical cardiovascular disease" (positive findings on the Rose questionnaire for angina or claudication, ankle-brachial index <0.9, or electrocardiographic abnormalities), and "no cardiovascular disease." Serum levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and the soluble receptors IL-6 soluble receptor, IL-2 soluble receptor, TNF soluble receptor I, and TNF soluble receptor II were assessed. Of those with IL-6 levels in the highest compared with the lowest tertile, the odds ratio (OR) for subclinical cardiovascular disease was 1.58 (95% confidence interval [CI] 1.26 to 1.97) and for clinical cardiovascular disease was 2.35 (95% CI 1.79 to 3.09). A similar association was found for TNF-alpha (OR 1.48, 95% CI 1.16 to 1.88 and OR 2.05, 95% CI 1.55 to 2.72, respectively). In adjusted analyses, CRP was not significantly associated with overall subclinical or clinical cardiovascular disease, although additional analyses did find a strong specific association between CRP and congestive heart failure (OR 1.64, 95% CI 1.11 to 2.41). Of the soluble cytokine receptors, only TNF soluble receptor I showed a significant association with clinical cardiovascular disease. Thus, our findings suggest an important role for IL-6 and TNF-alpha in clinical as well as subclinical cardiovascular disease. In this study, CRP had a weaker association with cardiovascular disease than the cytokines. [ABSTRACT FROM AUTHOR]

Background: Among older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research. The main objective of the Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial (NCT05764733) is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary WL-associated bone loss among 308 older (≥60 years) adults living with an indication for WL and bisphosphonate use., Methods: All participants will receive the same group-mediated dietary intervention targeting 8-10 % WL and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT + +PL); no RT and oral bisphosphonate (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and oral bisphosphonate (RT + +BIS). Total hip areal (a)BMD measured via dual-energy x-ray absorptiometry (DXA) is the primary, powered study outcome. Secondary skeletal outcome measures include femoral neck and lumbar spine aBMD, high resolution peripheral quantitative computed tomography (HRpQCT) bone assessments of the radius and tibia, and biomarkers of bone turnover., Discussion: BEACON will address an understudied, yet important, clinical research question by studying the independent and combined effects of two scalable intervention strategies aimed at optimizing skeletal integrity in older adults undergoing WL., Clinical Trials Registration: NCT05764733., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Obesity combined with heart failure with preserved ejection fraction (HFpEF) is the dominant form of HF among older persons. In a randomized trial, we previously showed that a 5-month calorie restriction (CR) program, with or without aerobic exercise training (AT), resulted in significant weight and fat loss and improved exercise capacity. However, little is known regarding the long-term effects of these outcomes after a short-term (5-month) intervention of CR with or without AT in older patients with obesity and HFpEF., Methods: Sixteen participants from either the CR or CR+AT who experienced significant weight loss ≥ 2 kg were reexamined after a long-term follow-up endpoint (28.0 ± 10.8 months) without intervention. The follow-up assessment included body weight and composition via dual-energy X-ray absorptiometry and exhaustive cardiopulmonary treadmill exercise testing., Results: Compared to the 5-month time-point intervention endpoint, at the long-term follow-up endpoint, mean body weight increased +5.2 ± 4.0 kg (90.7 ± 11.2 kg vs 95.9 ± 11.9; P < 0.001) due to increased fat mass (38.9 ± 9.3 vs 43.8 ± 9.8; P < 0.001) with no change in lean mass (49.6 ± 7.1 vs 49.9±7.6; P = 0.67), resulting in worse body composition (decreased lean-to-fat mass). Change in total mass was strongly and significantly correlated with change in fat mass (r = 0.75; P < 0.001), whereas there appeared to be a weaker correlation with change in lean mass (r = 0.50; P = 0.051). Additionally, from the end of the 5-month time-point intervention endpoint to the long-term follow-up endpoint, there were large, significant decreases in VO 2 peak (-2.2 ± 2.1 mL/kg/min; P = 0.003) and exercise time (-2.4 ± 2.6 min; P = 0.006). There appeared to be an inverse correlation between the change in VO 2 peak and the change in fat mass (r = -0.52; P = 0.062)., Conclusion: Although CR and CR+AT in older patients with obesity and HFpEF can improve body composition and exercise capacity significantly, these positive changes diminish considerably during long-term follow-up endpoints, and regained weight is predominantly adipose, resulting in worsened overall body composition compared to baseline. This suggests a need for long-term adherence strategies to prevent weight regain and maintain improvements in body composition and exercise capacity following CR in older patients with obesity and HFpEF., Competing Interests: Disclosures BU has received research funding from Novartis and Corvia. PHB has received honoraria as a consultant for Boston Scientific, Boehringer Ingelheim, Corvia Medical, and Merck. DWK has received honoraria as a consultant for Bayer, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer Ingelheim, Ketyo, Rivus, NovoNordisk, AstraZeneca‚ and Novartis, grant funding from Novartis, Bayer, NovoNordisk‚ and AstraZeneca‚ and has stock ownership in Gilead Sciences. All other authors report no disclosures. The manuscript is not under consideration elsewhere, nor have any of its contents been previously published. All authors have read and approved the manuscript. All authors contributed to the work by ICMJE guidelines. None of the other authors have any financial disclosures or conflicts of interest concerning this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.)

Greater perceived physical fatigability and lower skeletal muscle energetics are predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher=greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher=greater) after a slow treadmill walk. Participants from the Study of Muscle, Mobility and Aging (N=873) were 76.3±5.0 years old, 59.2% women, and 85.3% White. Higher muscle energetics (both in vivo and ex vivo ) were associated with lower perceived physical fatigability, all p<0.03. When stratified by sex, higher ATPmax was associated with lower PFS Physical for men only; higher max OXPHOS and max FAO OXPHOS were associated with lower RPE fatigability for both sexes. Higher skeletal muscle energetics were associated with 40-55% lower odds of being in the most (PFS≥25, RPE Fatigability≥12) vs least (PFS 0-4, RPE Fatigability 6-7) severe fatigability strata, all p<0.03. Being a woman was associated with 2-3 times higher odds of being in the most severe fatigability strata when controlling for ATPmax but not the in vivo measures (p<0.05). Better mitochondrial energetics were linked to lower fatigability and less severe fatigability in older adults. Findings imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging.

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 VO 2 peak 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). VO 2 peak (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 VO 2 peak 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 VO 2 peak 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 VO 2 peak values. Bland-Altman plot and regression analyses indicated predicted VO 2 peak 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., (© 2023 The American Geriatrics Society.)

Mitochondrial improvements resulting from behavioral interventions, such as diet and exercise, are systemic and apparent across multiple tissues. Here, we test the hypothesis that factors present in serum, and therefore circulating throughout the body, can mediate changes in mitochondrial function in response to intervention. To investigate this, we used stored serum from a clinical trial comparing resistance training (RT) and RT plus caloric restriction (RT + CR) to examine effects of blood borne circulating factors on myoblasts in vitro. We report that exposure to dilute serum is sufficient to mediate bioenergetic benefits of these interventions. Additionally, serum-mediated bioenergetic changes can differentiate between interventions, recapitulate sex differences in bioenergetic responses, and is linked to improvements in physical function and inflammation. Using metabolomics, we identified circulating factors associated with changes in mitochondrial bioenergetics and the effects of interventions. This study provides new evidence that circulating factors play a role in the beneficial effects of interventions that improve healthspan among older adults. Understanding the factors that drive improvements in mitochondrial function is a key step towards predicting intervention outcomes and developing strategies to countermand systemic age-related bioenergetic decline., (© 2023. The Author(s).)

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 (R2 = 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., (© 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.)

Competing Interests: Disclosures Dr Kitzman received honoraria as a consultant outside the present study for Bayer, Pfizer, Corvia Medical, Boehringer Ingelheim, Ketyo, Rivus, Novo Nordisk, AstraZeneca, and Novartis; grant funding from Novartis, Bayer, Pfizer, Novo Nordisk, and AstraZeneca; and has stock ownership in Gilead Sciences. The other authors report no conflicts.

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.)

Importance: The pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely understood. Multiple lines of evidence suggest that abnormal skeletal muscle metabolism is a key contributor, but the mechanisms underlying metabolic dysfunction remain unresolved., Objective: To evaluate the associations of skeletal muscle mitochondrial function using respirometric analysis of biopsied muscle fiber bundles from patients with HFpEF with exercise performance., Design, Setting, and Participants: In this cross-sectional study, muscle fiber bundles prepared from fresh vastus lateralis biopsies were analyzed by high-resolution respirometry to provide detailed analyses of mitochondrial oxidative phosphorylation, including maximal capacity and the individual contributions of complex I-linked and complex II-linked respiration. These bioenergetic data were compared between patients with stable chronic HFpEF older than 60 years and age-matched healthy control (HC) participants and analyzed for intergroup differences and associations with exercise performance. All participants were treated at a university referral center, were clinically stable, and were not undergoing regular exercise or diet programs. Data were collected from March 2016 to December 2017, and data were analyzed from November 2020 to May 2021., Main Outcomes and Measures: Skeletal muscle mitochondrial function, including maximal capacity and respiration linked to complex I and complex II. Exercise performance was assessed by peak exercise oxygen consumption, 6-minute walk distance, and the Short Physical Performance Battery., Results: Of 72 included patients, 50 (69%) were women, and the mean (SD) age was 69.6 (6.1) years. Skeletal muscle mitochondrial function measures were all markedly lower in skeletal muscle fibers obtained from patients with HFpEF compared with HCs, even when adjusting for age, sex, and body mass index. Maximal capacity was strongly and significantly correlated with peak exercise oxygen consumption (R = 0.69; P < .001), 6-minute walk distance (R = 0.70; P < .001), and Short Physical Performance Battery score (R = 0.46; P < .001)., Conclusions and Relevance: In this study, patients with HFpEF had marked abnormalities in skeletal muscle mitochondrial function. Severely reduced maximal capacity and complex I-linked and complex II-linked respiration were associated with exercise intolerance and represent promising therapeutic targets.

Cryoglobulinemia is an uncommon blood dyscrasia that can manifest itself in the lower extremity. Due to the insidious nature of this disease, dermatological symptoms and ulcerations can easily be mistaken for more common entities. The authors present an overview of cryoglobulinemia and a case report of a patient with lower extremity manifestations of this disorder. This can provide specific guidance on the steps necessary to accurately establish the diagnosis of cryoglobulinemia or rule it out and pursue other etiologies causing lower extremity ulceration.

Background: We have shown that combined caloric restriction (CR) and aerobic exercise training (AT) improve peak exercise O 2 consumption (VO 2peak ), and quality-of-life in older patients with obese heart failure with preserved ejection fraction. However, ≈35% of weight lost during CR+AT was skeletal muscle mass. We examined whether addition of resistance training (RT) to CR+AT would reduce skeletal muscle loss and further improve outcomes., Methods: This study is a randomized, controlled, single-blind, 20-week trial of RT+CR+AT versus CR+AT in 88 patients with chronic heart failure with preserved ejection fraction and body mass index (BMI) ≥28 kg/m 2 . Outcomes at 20 weeks included the primary outcome (VO 2peak ); MRI and dual X-ray absorptiometry; leg muscle strength and quality (leg strength ÷ leg skeletal muscle area); and Kansas City Cardiomyopathy Questionnaire., Results: Seventy-seven participants completed the trial. RT+CR+AT and CR+AT produced nonsignificant differences in weight loss: mean (95% CI): -8 (-9, -7) versus -9 (-11, -8; P =0.21). RT+CR+AT and CR+AT had non-significantly differences in the reduction of body fat [-6.5 (-7.2, -5.8) versus -7.4 (-8.1, -6.7) kg] and skeletal muscle [-2.1 (-2.7, -1.5) versus -2.1 (-2.7, -1.4) kg] ( P =0.20 and 0.23, respectively). RT+CR+AT produced significantly greater increases in leg muscle strength [4.9 (0.7, 9.0) versus -1.1 (-5.5, 3.2) Nm, P =0.05] and leg muscle quality [0.07 (0.03, 0.11) versus 0.02 (-0.02, 0.06) Nm/cm 2 , P =0.04]. Both RT+CR+AT and CR+AT produced significant improvements in VO 2peak [108 (958, 157) versus 80 (30, 130) mL/min; P =0.001 and 0.002, respectively], and Kansas City Cardiomyopathy Questionnaire score [17 (12, 22) versus 23 (17, 28); P =0.001 for both], with no significant between-group differences. Both RT+CR+AT and CR+AT significantly reduced LV mass and arterial stiffness. There were no study-related serious adverse events., Conclusions: In older obese heart failure with preserved ejection fraction patients, CR+AT produces large improvements in VO 2peak and quality-of-life. Adding RT to CR+AT increased leg strength and muscle quality without attenuating skeletal muscle loss or further increasing VO 2peak or quality-of-life., Registration: URL: https://ClincalTrials.gov; Unique identifier: NCT02636439.

Background: Prior work shows caloric restriction (CR) can improve physical function among older adults living with obesity. However, the contribution of starting weight and inflammatory burden to CR-associated functional improvements is unclear. The primary purpose of this study was to determine if CR-associated gait speed change varied by body mass index (BMI) and plasma interleukin 6 (IL-6) at baseline and secondarily to determine the contribution of BMI change and IL-6 change to gait speed change., Design, Setting, Participants: Data from eight randomized control trials were pooled, with 1184 participants randomized to CR (n=661) and No CR (n=523) conditions. All studies assessed outcomes before and five or six months after assignment to CR or No CR., Measurements: BMI and IL-6 were assessed at baseline using standard procedures. Gait speed was assessed with the six-minute walk test or 400m walk test. Baseline BMI/IL-6 subgroups were constructed using BMI≥35 kg/m2 and IL-6>2.5 pg/mL thresholds. Participants with BMI≥35 kg/m2 were grouped into class 2+ obesity and BMI<35 kg/m2 into class 1- obesity; IL-6>2.5 pg/mL were grouped into high IL-6, and <2.5 pg/mL as low IL-6 (class 2+ obesity/high IL-6: n=288, class 2+ obesity/low IL-6: n=143, class 1- obesity/high IL-6: n=354, or class 1- obesity/low IL-6: n=399). All analyses used adjusted general linear models., Results: Gait speed significantly improved with CR versus non-CR [mean difference: +0.02 m/s (95% CI: 0.01, 0.04)]. CR assignment significantly interacted with BMI/IL-6 subgroup membership (p=0.03). Greatest gait speed improvement was observed in the class 2+ obesity/high IL-6 subgroup [+0.07 m/s (0.03, 0.10)]. No other subgroups observed significant gait speed change. For each unit decrease in BMI, gait speed change increased by +0.02 m/s (p<0.001; R2=0.26), while log IL-6 change did not significantly affect gait speed change [+0.01 m/s (p=0.20)]., Conclusions: Only the class 2+ obesity/high IL-6 subgroup significantly improved gait speed in response to CR. Improvement in gait speed in this subgroup was driven by a larger decrease in BMI, but not IL-6, in response to CR. Individuals with class 2+ obesity and high IL-6 are most likely to show improved gait speed in response to CR, with improvement predominantly driven by reductions in BMI., Competing Interests: There are no conflicts of interest.

Background: The purpose of this study was to examine whether select baseline characteristics influenced the likelihood of an overweight/obese, older adult experiencing a clinically meaningful gait speed response (±0.05 m/s) to caloric restriction (CR)., Methods: Individual level data from 1 188 older adults participating in 8, 5/6-month, weight loss interventions were pooled, with treatment arms collapsed into CR (n = 667) or no CR (NoCR; n = 521) categories. Exercise assignment was equally distributed across groups (CR: 65.3% vs NoCR: 65.4%) and did not interact with CR (p = .88). Poisson risk ratios (95% confidence interval [CI]) were used to examine whether CR assignment interacted with select baseline characteristic subgroups: age (≥65 years), sex (female/male), race (Black/White), body mass index (BMI; ≥35 kg/m2), comorbidity (diabetes, hypertension, cardiovascular disease) status (yes/no), gait speed (<1.0 m/s), or inflammatory burden (C-reactive protein ≥3 mg/L, interleukin-6 ≥2.5 pg/mL) to influence achievement of ±0.05 m/s fast-paced gait speed change. Main effects were also examined., Results: The study sample (69.5% female, 80.1% White) was 67.6 ± 5.3 years old with a BMI of 33.8 ± 4.4 kg/m2. Average weight loss achieved in the CR versus NoCR group was -8.3 ± 5.9% versus -1.1 ± 3.8%; p < .01. No main effect of CR was observed on the likelihood of achieving a clinically meaningful gait speed improvement (risk ratio [RR]: 1.09 [95% CI: 0.93, 1.27]) or gait speed decrement (RR: 0.77 [95% CI: 0.57, 1.04]). Interaction effects were nonsignificant across all subgroups., Conclusion: The proportion of individuals experiencing a clinically meaningful gait speed change was similar for CR and NoCR conditions. This finding is consistent across several baseline subgroupings., (© The Author(s) 2021. 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.)

Clinical trials conventionally test aggregate mean differences and assume homogeneous variances across treatment groups. However, significant response heterogeneity may exist. The purpose of this study was to model treatment response variability using gait speed change among older adults participating in caloric restriction (CR) trials. Eight randomized controlled trials (RCTs) with five- or six-month assessments were pooled, including 749 participants randomized to CR and 594 participants randomized to non-CR (NoCR). Statistical models compared means and variances by CR assignment and exercise assignment or select subgroups, testing for treatment differences and interactions for mean changes and standard deviations. Continuous equivalents of dichotomized variables were also fit. Models used a Bayesian framework, and posterior estimates were presented as means and 95% Bayesian credible intervals (BCI). At baseline, participants were 67.7 (SD = 5.4) years, 69.8% female, and 79.2% white, with a BMI of 33.9 (4.4) kg/m2. CR participants reduced body mass [CR: -7.7 (5.8) kg vs. NoCR: -0.9 (3.5) kg] and increased gait speed [CR: +0.10 (0.16) m/s vs. NoCR: +0.07 (0.15) m/s] more than NoCR participants. There were no treatment differences in gait speed change standard deviations [CR-NoCR: -0.002 m/s (95% BCI: -0.013, 0.009)]. Significant mean interactions between CR and exercise assignment [0.037 m/s (95% BCI: 0.004, 0.070)], BMI [0.034 m/s (95% BCI: 0.003, 0.066)], and IL-6 [0.041 m/s (95% BCI: 0.009, 0.073)] were observed, while variance interactions were observed between CR and exercise assignment [-0.458 m/s (95% BCI: -0.783, -0.138)], age [-0.557 m/s (95% BCI: -0.900, -0.221)], and gait speed [-0.530 m/s (95% BCI: -1.018, -0.062)] subgroups. Caloric restriction plus exercise yielded the greatest gait speed benefit among older adults with obesity. High BMI and IL-6 subgroups also improved gait speed in response to CR. Results provide a novel statistical framework for identifying treatment heterogeneity in RCTs., Competing Interests: The authors have declared that no competing interests exist.

Objective: The goal of this study was to determine whether the degree of weight loss after 6 months of a behavior-based intervention is related to baseline connectivity within two functional networks (FNs) of interest, FN1 and FN2, in a group of older adults with obesity., Methods: Baseline functional magnetic resonance imaging data were collected following an overnight fast in 71 older adults with obesity involved in a weight-loss intervention. Functional brain networks in a resting state and during a food-cue task were analyzed using a mixed-regression framework to examine the relationships between baseline networks and 6-month change in weight., Results: During the resting condition, the relationship of baseline brain functional connectivity and network clustering in FN1, which includes the visual cortex and sensorimotor areas, was significantly associated with 6-month weight loss. During the food-cue condition, 6-month weight loss was significantly associated with the relationship between baseline brain connectivity and network global efficiency in FN2, which includes executive control, attention, and limbic regions., Conclusion: These findings provide further insight into complex functional circuits in the brain related to successful weight loss and may ultimately aid in developing tailored behavior-based treatment regimens that target specific brain circuitry., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)

Objective: To determine whether long-term diet (D) and exercise (E) interventions, alone or in combination (D+E), have beneficial effects for older adults with knee osteoarthritis (OA) 3.5 years after the interventions end., Methods: This is a secondary analysis of a subset (n = 94) of the first 184 participants who had successfully completed the Intensive Diet and Exercise in Arthritis (IDEA) trial (n = 399) and who consented to follow-up testing. Participants were older (age ≥55 years), overweight, and obese adults with radiographic and symptomatic knee OA in at least 1 knee who completed 1.5-year D+E (n = 27), D (n = 35), or E (n = 32) interventions and returned for 5-year follow-up testing an average of 3.5 years later., Results: During the 3.5-years following the interventions, weight regain in D+E and D was 5.9 kg (7%) and 3.1 kg (4%), respectively, with a 1-kg (1%) weight loss in E. Compared to baseline, weight (D+E -3.7 kg [P = 0.0007], D -5.8 kg [P < 0.0001], E -2.9 kg [P = 0.003]) and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale scores (D+E -1.2 [P = 0.03], D -1.5 [P = 0.001], E -1.6 [P = 0.0008]) were lower in each group at the 5-year follow-up. The effect of group assignment at the 5-year follow-up was significant for body weight, with D being less than E (-3.5 kg; P = 0.04)., Conclusion: Older adults with knee OA who completed 1.5-year D or D+E interventions experienced partial weight regain 3.5 years later; yet, relative to baseline, they preserved statistically significant changes in weight loss and reductions in knee pain., (© 2021 American College of Rheumatology.)

Intermediate endpoints are needed to evaluate the effect of interventions targeting the biology of aging in clinical trials. A working group identified five blood-based biomarkers that may serve such a purpose as an integrated index. We evaluated the responsiveness of the panel to caloric restriction or aerobic exercise in the context of a randomized clinical trial conducted in patients with heart failure with preserved ejection fraction (HFpEF) with obese phenotype who were predominantly female. Obese HFpEF is highly prevalent in women, and is a geriatric syndrome whose disease pathology is driven by non-cardiac factors and shared drivers of aging. We measured serum Interleukin-6, TNF-α-receptor-I, growth differentiating factor-15, cystatin C, and N-terminal pro-b-type natriuretic peptide at baseline and after 20 weeks in older participants with stable obese HFpEF participating in a randomized, controlled, 2 × 2 factorial trial of caloric restriction and/or aerobic exercise. We calculated a composite biomarker index, summing baseline quintile scores for each biomarker, and analyzed the effect of the interventions on the index and individual biomarkers and their associations with changes in physical performance. This post hoc analysis included 88 randomized participants (71 women [81%]). The mean ± SD age was 66.6 ± 5.3 years, and body mass index (BMI) was 39.3 ± 6.3 kg/m 2 . Using mixed models, mean values of the biomarker index improved over 20 weeks with caloric restriction (- 0.82 [Formula: see text] 0.58 points, p = 0.05), but not with exercise (- 0.28 [Formula: see text] 0.59 points, p = [Formula: see text]), with no evidence of an interaction effect of CR [Formula: see text] EX [Formula: see text] time (p = 0.80) with adjustment for age, gender, and BMI. At baseline, the biomarker index was inversely correlated with 6-min walk distance, scores on the short physical performance battery, treadmill test peak workload and exercise time to exhaustion (all [Formula: see text] s  = between - 0.21 and - 0.24). A reduction in the biomarker index was also associated with increased 4-m usual walk speed ([Formula: see text] s  =  - 0.31). Among older patients with chronic obese HFpEF, caloric restriction improved a biomarker index designed to reflect biological aging. Moreover, the index was associated with physical performance and exercise tolerance., (© 2022. The Author(s), under exclusive licence to American Aging Association.)

Background: This report investigates the impact of a remote physical activity intervention on self-efficacy, satisfaction with functioning, and health-related quality of life (HRQOL) as assessed by the SF-36 in obese older adults with chronic pain. The intervention was group-mediated in nature and based in social cognitive theory and mindfulness-based relapse prevention., Methods: Participants (N = 28; 70.21 ± 5.22 years) were randomly assigned to receive either the active intervention, which focused on reducing caloric intake and increasing steps across the day or to a waitlist control condition., Results: Over 12 weeks, intervention participants reported a moderate, positive improvement in self-efficacy for walking relative to control. They also reported large magnitude improvements in satisfaction for physical functioning as well as improvements on pain and the physical functioning subscales of the SF-36., Conclusions: These findings expand on previous research showing similar effects in response to structured exercise, this time via a protocol that is likely to be scalable and sustainable for many older adults. Additional work on larger and more diverse samples is warranted., (© 2021. International Society of Behavioral Medicine.)

Objective: This study aimed to determine the impact of dietary weight loss (WL) plus aerobic exercise (EX) and a "move more, more often" approach to activity promotion (SitLess; SL) on WL and maintenance., Methods: Low-active older adults (age 65-86 years) with obesity were randomized to WL+EX, WL+SL, or WL+EX+SL. Participants received a social-cognitive group-mediated behavioral WL program for 6 months, followed by a 12-month maintenance period. EX participants received guided walking exercise with the goal of walking 150 min/wk. SL attempted to achieve a step goal by moving frequently during the day. The primary outcome was body weight at 18 months, with secondary outcomes including weight regain from 6 to 18 months and objectively assessed physical activity and sedentary behavior at each time point., Results: All groups demonstrated significant WL over 6 months (p < 0.001), with no group differences. Groups that received SL improved total activity time (p ≤ 0.05), and those who received EX improved moderate-to-vigorous activity time (p = 0.003). Over the 12-month follow-up period, those who received WL+EX demonstrated greater weight regain (5.2 kg; 95% CI: 3.5-6.9) relative to WL+SL (2.4 kg; 95% CI: 0.8-4.0)., Conclusions: Pairing dietary WL with a recommendation to accumulate physical activity contributed to similar WL and less weight regain compared with traditional aerobic exercise., (© 2021 The Obesity Society.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Obesity may accelerate age-related increases in aortic stiffness. Although aerobic exercise training generally has favorable effects on aortic structure and function, exercise alone may not be sufficient to improve aortic stiffness in older adults with obesity. We determined the effects of aerobic exercise training with and without moderate- to high-caloric restriction (CR) on the structure and function of the proximal aorta in 160 older (65-79 years) men and women with obesity (body mass index=30-45 kg/m 2 )., Methods: Participants were randomly assigned to 1 of 3 groups: aerobic exercise training only (treadmill 4 days/week for 30 minutes at 65% to 70% of heart rate reserve; n=56), aerobic exercise training plus moderate CR (n=55), or aerobic exercise training plus more intensive CR (n=49) for 20 weeks. Aortic pulse wave velocity, aortic distensibility, and other measures of aortic structure and function were assessed by cardiovascular magnetic resonance imaging. Pearson correlation coefficients were examined to assess associations between changes in proximal aortic stiffness and changes in fitness, fatness, and other potential confounders., Results: Weight loss in the aerobic exercise training plus moderate CR (-8.0 kg [95% CI, -9.17 to -6.87]) and aerobic exercise training plus more intensive CR (-8.98 kg [95% CI, -10.23 to -7.73) groups was significantly greater compared with the aerobic exercise training-only group (-1.66 kg [95% CI, -2.94 to -0.38]; P <0.017 for both). There were significant treatment effects for descending aorta distensibility ( P =0.008) and strain ( P =0.004) and aortic arch pulse wave velocity ( P =0.01) with the aerobic exercise training plus moderate CR group having a 21% increase in distensibility ( P =0.016) and an 8% decrease in pulse wave velocity ( P =0.058). None of the aortic stiffness measures changed significantly in the aerobic exercise training-only or aerobic exercise training plus more intensive CR groups, and there were no significant changes in any other measure of aortic structure or function in these groups. Overall, increases in aortic distensibility were correlated with improvements in body weight and body fat distribution, but these associations were not statistically significant after adjustment for multiple comparisons., Conclusions: In older adults with obesity, combining aerobic exercise with moderate CR leads to greater improvements in proximal aortic stiffness than exercise alone. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT01048736.