The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy (31P‐MRS) in 385 participants (256 women, 129 men), aged 24–97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), kPCr, was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography–tandem mass spectrometry. Adults in the highest quartile of kPCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine‐learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of kPCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults.

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BACKGROUND 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 lifestyle practices is unclear. Therefore, we tested the hypothesis that physical activity is associated with better oxidative capacity, independent of age. DESIGN 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). SETTING NIA IRP Clinical Research Unit, Baltimore, MD. PARTICIPANTS Participants included 384 adults (54.7% women), aged 22 to 92 years, seen between 2013 and 2017. MEASUREMENTS Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the postexercise time constant (τPCr; in seconds) for phosphocreatine (PCr) recovery, with lower values of τPCr, (ie, 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. RESULTS In linear regression models, higher τPCr was associated with older age (standardized β = .39; P < .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 τPCr (βage = .22; P < .001) and had a smaller standardized regression coefficient than MVPA (βMVPA = −.33; P < .001). After adjusting for health status, education, and smoking history, the standardized regression coefficient for age decreased 12% (βage = .20; P = .003), while the standardized coefficient for MVPA decreased only 3% (βMVPA = −.32; P < .001). CONCLUSION 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. J Am Geriatr Soc 67:1695–1699, 2019