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Objective: Our objective was to investigate the overall and sex‐specific relationships between the presence and severity of knee osteoarthritis (KOA) and muscle composition, power, and energetics in older adults. Methods: Male and female patients (n = 655, mean ± SD age 76.1 ± 4.9 years; 57% female) enrolled in the Study of Muscle, Mobility, and Aging completed standing knee radiographs and knee pain assessments. Participants were divided into three groups using Kellgren‐Lawrence grade (KLG) of KOA severity (0–1, 2, or 3–4). Outcome measures included whole‐body muscle mass, thigh fat‐free muscle (FFM) volume and muscle fat infiltration (MFI), leg power, specific power (power normalized to muscle volume), and muscle mitochondrial energetics. Results: Overall, the presence and severity of KOA is associated with greater MFI, lower leg power and specific power, and reduced oxidative phosphorylation (P trend < 0.036). Sex‐specific analysis revealed reduced energetics only in female patients with KOA (P trend < 0.007) compared to female patients without KOA. In models adjusted for age, sex, race, nonsteroidal anti‐inflammatory drug administration, site or technician, physical activity, height, and participants with abdominal adiposity with KLG 3 to 4 had greater MFI (mean 0.008%, 95% confidence interval [CI] 0.004%–0.011%) and lower leg power (mean −51.56 W, 95% CI −74.03 to −29.10 W) and specific power (mean −5.38 W/L, 95% CI −7.31 to −3.45 W/L) than those with KLG 0 to 1. No interactions were found between pain and KLG status. Among those with KOA, MFI and oxidative phosphorylation were associated with thigh FFM volume, leg power, and specific power. Conclusion: Muscle health is associated with the presence and severity of KOA and differs by sex. Although muscle composition and power are lower in both male and female patients with KOA, regardless of pain status, mitochondrial energetics is reduced only in female patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine associations of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults. Methods: Cross‐sectional data from 829 adults ≥70 years of age were used. Abdominal, subcutaneous, and visceral AT and thigh muscle fat infiltration (MFI) were quantified by magnetic resonance imaging. SM mitochondrial energetics were characterized in vivo (31P‐magnetic resonance spectroscopy; ATPmax) and ex vivo (high‐resolution respirometry maximal oxidative phosphorylation [OXPHOS]). ActivPal was used to measure physical activity ([PA]; step count). Linear regression adjusted for covariates was applied, with sequential adjustment for BMI and PA. Results: Independent of BMI, total abdominal AT (standardized [Std.] β = −0.21; R2 = 0.09) and visceral AT (Std. β = −0.16; R2 = 0.09) were associated with ATPmax (p < 0.01; n = 770) but not following adjustment for PA (p ≥ 0.05; n = 658). Visceral AT (Std. β = −0.16; R2 = 0.25) and thigh MFI (Std. β = −0.11; R2 = 0.24) were associated with carbohydrate‐supported maximal OXPHOS independent of BMI and PA (p < 0.05; n = 609). Total abdominal AT (Std. β = −0.19; R2 = 0.24) and visceral AT (Std. β = −0.17; R2 = 0.24) were associated with fatty acid‐supported maximal OXPHOS independent of BMI and PA (p < 0.05; n = 447). Conclusions: Skeletal MFI and abdominal visceral, but not subcutaneous, AT are inversely associated with SM mitochondrial bioenergetics in older adults independent of BMI. Associations between ectopic AT and in vivo mitochondrial bioenergetics are attenuated by PA. [ABSTRACT FROM AUTHOR]

Exercise‐induced perturbation of skeletal muscle metabolites is a probable mediator of long‐term health benefits in older adults. Although specific metabolites have been identified to be impacted by age, physical activity and exercise, the depth of coverage of the muscle metabolome is still limited. Here, we investigated resting and exercise‐induced metabolite distribution in muscle from well‐phenotyped older adults who were active or sedentary, and a group of active young adults. Percutaneous biopsies of the vastus lateralis were obtained before, immediately after and 3 h following a bout of endurance cycling. Metabolite profile in muscle biopsies was determined by tandem mass spectrometry. Mitochondrial energetics in permeabilized fibre bundles was assessed by high resolution respirometry and fibre type proportion was assessed by immunohistology. We found that metabolites of the kynurenine/tryptophan pathway were impacted by age and activity. Specifically, kynurenine was elevated in muscle from older adults, whereas downstream metabolites of kynurenine (kynurenic acid and NAD+) were elevated in muscle from active adults and associated with cardiorespiratory fitness and muscle oxidative capacity. Acylcarnitines, a potential marker of impaired metabolic health, were elevated in muscle from physically active participants. Surprisingly, despite baseline group difference, acute exercise‐induced alterations in whole‐body substrate utilization, as well as muscle acylcarnitines and ketone bodies, were remarkably similar between groups. Our data identified novel muscle metabolite signatures that associate with the healthy ageing phenotype provoked by physical activity and reveal that the metabolic responsiveness of muscle to acute endurance exercise is retained [NB]:AUTHOR: Please ensure that the appropriate material has been provide for Table S2, as well as for Figures S1 to S7, as also cited in the text with age regardless of activity levels. Key points: Kynurenine/tryptophan pathway metabolites were impacted by age and physical activity in human muscle, with kynurenine elevated in older muscle, whereas downstream products kynurenic acid and NAD+ were elevated in exercise‐trained muscle regardless of age.Acylcarnitines, a marker of impaired metabolic health when heightened in circulation, were elevated in exercise‐trained muscle of young and older adults, suggesting that muscle act as a metabolic sink to reduce the circulating acylcarnitines observed with unhealthy ageing.Despite the phenotypic differences, the exercise‐induced response of various muscle metabolite pools, including acylcarnitine and ketone bodies, was similar amongst the groups, suggesting that older adults can achieve the metabolic benefits of exercise seen in young counterparts. [ABSTRACT FROM AUTHOR]

Abstract: Background: The concept of mitochondrial dysfunction in ageing muscle is highly controversial. In addition, emerging evidence suggests that reduced muscle oxidative capacity and efficiency underlie the aetiology of mobility loss in older adults. Here, we hypothesized that studying well‐phenotyped older cohorts across a wide range of physical activity would unveil a range of mitochondrial function in skeletal muscle and in turn allow us to more clearly examine the impact of age per se on mitochondrial energetics. This also enabled us to more clearly define the relationships between mitochondrial energetics and muscle lipid content with clinically relevant assessments of muscle and physical function. Methods: Thirty‐nine volunteers were recruited to the following study groups: young active (YA, n = 2 women/8 men, age = 31.2 ± 5.4 years), older active (OA, n = 2 women/8 men, age = 67.5 ± 2.7 years), and older sedentary (OS, n = 8 women/11 men, age = 70.7 ± 4.7 years). Participants completed a graded exercise test to determine fitness (VO2peak), a submaximal exercise test to determine exercise efficiency, and daily physical activity was recorded using a tri‐axial armband accelerometer. Mitochondrial energetics were determined by (i) 31P magnetic resonance spectroscopy and (ii) respirometry of fibre bundles from vastus lateralis biopsies. Quadriceps function was assessed by isokinetic dynamometry and physical function by the short physical performance battery and stair climb test. Results: Daily physical activity energy expenditure was significantly lower in OS, compared with YA and OA groups. Despite fitness being higher in YA compared with OA and OS, mitochondrial respiration, maximum mitochondrial capacity, Maximal AT P production/ Oxygen consumption (P/O) ratio, and exercise efficiency were similar in YA and OA groups and were significantly lower in OS. P/O ratio was correlated with exercise efficiency. Time to complete the stair climb and repeated chair stand tests were significantly greater for OS. Interestingly, maximum mitochondrial capacity was related to muscle contractile performance and physical function. Conclusions: Older adults who maintain a high amount of physical activity have better mitochondrial capacity, similar to highly active younger adults, and this is related to their better muscle quality, exercise efficiency, and physical performance. This suggests that mitochondria could be an important therapeutic target for sedentary ageing associated conditions including sarcopenia, dynapenia, and loss of physical function. [ABSTRACT FROM AUTHOR]

Objective: Roux-en-Y gastric bypass (RYGB) surgery can cause profound weight loss and improve overall cardiometabolic risk factors. Exercise (EX) training following RYGB can provide additional improvements in insulin sensitivity (SI ) and cardiorespiratory fitness. However, it remains unknown whether a specific amount of EX post-RYGB is required to achieve additional benefits.Methods: We performed a post hoc analysis of participants who were randomized into either a 6-month structured EX program or a health education control (CON). The EX group (n = 56) was divided into tertiles according to the amount of weekly exercise performed, compared with CON (n = 42): low-EX = 54 ± 8; middle-EX = 129 ± 4; and high-EX = 286 ± 40 min per week.Results: The high-EX lost a significantly greater amount of body weight, total fat mass, and abdominal deep subcutaneous abdominal fat compared with CON (P < 0.005). SI improved to a greater extent in both the middle-EX and high-EX compared with CON (P < 0.04). Physical fitness (VO2 max) significantly improved in the high-EX (9.3% ± 4.2%) compared with CON (-6.0 ± 2.4%) (P < 0.001). Skeletal muscle mitochondrial State 4 (P < 0.002) and 3 (P < 0.04) respiration was significantly higher in the high-EX compared with CON.Conclusions: A modest volume of structured exercise provides additional improvements in insulin sensitivity following RYGB, but higher volumes of exercise are required to induce additional weight loss, changes in body composition, and improvements in cardiorespiratory fitness and skeletal muscle mitochondrial capacity. [ABSTRACT FROM AUTHOR]