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      Moderate‐to‐Vigorous Physical Activity Is Associated With Higher Muscle Oxidative Capacity in Older Adults

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          Abstract

          Age-related decline in muscle oxidative capacity reduces muscle function and physical performance leading to disability and frailty. Whether age-related decline in oxidative capacity is modified by exercise and other life-style practices is unclear. Therefore, we tested the hypothesis that physical activity is associated with better oxidative capacity independent of age. Cross-sectional study performed in the Baltimore Longitudinal Study of Aging conducted by the Intramural Research Program (IRP) of the National Institute on Aging (NIA). NIA IRP Clinical Research Unit, Baltimore, MD. Participants included 384 adults (54.7% women) aged 22 to 92 years seen between 2013 and 2017. Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the post-exercise time constant (τ PCr , in seconds) for phosphocreatine (PCr) recovery, with lower values of τ PCr, (i.e, more rapid recovery of PCr levels after exercise) reflecting greater oxidative capacity. Time spent in moderate-to-vigorous physical activity (MVPA) was assessed using wearable accelerometers that participants wore 5.9 ± 0.9 consecutive days in the free-living environment. In linear regression models, higher τ PCr was associated with older age (standardized β = 0.39, p-value <.001) after adjusting for sex, race, height and weight. After including MVPA as an independent variable, the standardized regression coefficient of age decreased by 40%, but remained associated with τ PCr (β age = 0.22, p -value <.001) and had a smaller standardized regression coefficient than MVPA (β MVPA = −0.33, p -value <.001). After adjusting for health status, education and smoking history, the standardized regression coefficient for age decreased 12% (β age = 0.20, p -value = .003), while the standardized coefficient for MVPA decreased only 3% (β MVPA = −0.32, p-value <.001). Study findings suggest that MVPA is strongly associated with muscle oxidative capacity independent of age, providing mechanistic insights into the health benefits of exercise in older age.

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          Most cited references24

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          Decline in skeletal muscle mitochondrial function with aging in humans.

          Cumulative mtDNA damage occurs in aging animals, and mtDNA mutations are reported to accelerate aging in mice. We determined whether aging results in increased DNA oxidative damage and reduced mtDNA abundance and mitochondrial function in skeletal muscle of human subjects. Studies performed in 146 healthy men and women aged 18-89 yr demonstrated that mtDNA and mRNA abundance and mitochondrial ATP production all declined with advancing age. Abundance of mtDNA was positively related to mitochondrial ATP production rate, which in turn, was closely associated with aerobic capacity and glucose tolerance. The content of several mitochondrial proteins was reduced in older muscles, whereas the level of the oxidative DNA lesion, 8-oxo-deoxyguanosine, was increased, supporting the oxidative damage theory of aging. These results demonstrate that age-related muscle mitochondrial dysfunction is related to reduced mtDNA and muscle functional changes that are common in the elderly.
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            Oxidative capacity and ageing in human muscle.

            This study determined the decline in oxidative capacity per volume of human vastus lateralis muscle between nine adult (mean age 38.8 years) and 40 elderly (mean age 68.8 years) human subjects (age range 25-80 years). We based our oxidative capacity estimates on the kinetics of changes in creatine phosphate content ([PCr]) during recovery from exercise as measured by (31)P magnetic resonance (MR) spectroscopy. A matched muscle biopsy sample permitted determination of mitochondrial volume density and the contribution of the loss of mitochondrial content to the decline in oxidative capacity with age. The maximal oxidative phosphorylation rate or oxidative capacity was estimated from the PCr recovery rate constant (k(PCr)) and the [PCr] in accordance with a simple electrical circuit model of mitochondrial respiratory control. Oxidative capacity was 50 % lower in the elderly vs. the adult group (0.61 +/- 0.04 vs. 1.16 +/- 0.147 mM ATP s(-1)). Mitochondrial volume density was significantly lower in elderly compared with adult muscle (2.9 +/- 0.15 vs. 3.6 +/- 0.11 %). In addition, the oxidative capacity per mitochondrial volume (0.22 +/- 0.042 vs. 0.32 +/- 0.015 mM ATP (s %)(-1)) was reduced in elderly vs. adult subjects. This study showed that elderly subjects had nearly 50 % lower oxidative capacity per volume of muscle than adult subjects. The cellular basis of this drop was a reduction in mitochondrial content, as well as a lower oxidative capacity of the mitochondria with age.
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              Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults.

              Lower ambulatory performance with aging may be related to a reduced oxidative capacity within skeletal muscle. This study examined the associations between skeletal muscle mitochondrial capacity and efficiency with walking performance in a group of older adults. Thirty-seven older adults (mean age 78 years; 21 men and 16 women) completed an aerobic capacity (VO2 peak) test and measurement of preferred walking speed over 400 m. Maximal coupled (State 3; St3) mitochondrial respiration was determined by high-resolution respirometry in saponin-permeabilized myofibers obtained from percutanous biopsies of vastus lateralis (n = 22). Maximal phosphorylation capacity (ATPmax) of vastus lateralis was determined in vivo by (31)P magnetic resonance spectroscopy (n = 30). Quadriceps contractile volume was determined by magnetic resonance imaging. Mitochondrial efficiency (max ATP production/max O2 consumption) was characterized using ATPmax per St3 respiration (ATPmax/St3). In vitro St3 respiration was significantly correlated with in vivo ATPmax (r (2) = .47, p = .004). Total oxidative capacity of the quadriceps (St3*quadriceps contractile volume) was a determinant of VO2 peak (r (2) = .33, p = .006). ATPmax (r (2) = .158, p = .03) and VO2 peak (r (2) = .475, p < .0001) were correlated with preferred walking speed. Inclusion of both ATPmax/St3 and VO2 peak in a multiple linear regression model improved the prediction of preferred walking speed (r (2) = .647, p < .0001), suggesting that mitochondrial efficiency is an important determinant for preferred walking speed. Lower mitochondrial capacity and efficiency were both associated with slower walking speed within a group of older participants with a wide range of function. In addition to aerobic capacity, lower mitochondrial capacity and efficiency likely play roles in slowing gait speed with age.
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                Author and article information

                Journal
                Journal of the American Geriatrics Society
                J Am Geriatr Soc
                Wiley
                0002-8614
                1532-5415
                May 10 2019
                August 2019
                May 22 2019
                August 2019
                : 67
                : 8
                : 1695-1699
                Affiliations
                [1 ]Translational Gerontology Branch, Intramural Research ProgramNational Institute on Aging, National Institutes of Health Baltimore Maryland
                [2 ]Department of Medicine, Division of Geriatric Medicine and Gerontology, Center on Aging and HealthJohn Hopkins University School of Medicine Baltimore Maryland
                [3 ]Laboratory of Clinical Investigation, Intramural Research ProgramNational Institute on Aging, National Institutes of Health Baltimore Maryland
                [4 ]Department of EpidemiologyJohn Hopkins Bloomberg School of Public Health Baltimore Maryland
                Article
                10.1111/jgs.15991
                6684385
                31116422
                1d1b88b0-fc2b-4f4a-9a9b-2a45a78b0356
                © 2019

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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