Muscle function in fit and (pre-)frail males and females

AbstractBackground: A decreased intramuscular carnitine status with aging may contribute to frailty and fatigue, but studies are often confounded by sex-heterogeneity and lack of control groups. We hypothesize that muscle carnitine deficiency is associated with (pre-)frailty, diminished physical performance and altered mitochondrial function, possibly in a sex-dependent manner. This was tested in well-matched age groups, allowing gender-specific analyses. Methods: A cross-sectional study was performed in well-matched fit (n = 15) and (pre-)frail (n = 13) old males as well as in fit (n = 15) and (pre-)frail (n = 11) old females, using young males (n = 13) and females (n = 13) as healthy controls. In the elderly, frailty was assessed according to the Fried criteria and physical performance was determined by 400-m walk test, short physical performance battery and handgrip strength. Acylcarnitine status was assessed in muscle biopsies and blood plasma using liquid chromatography-tandem mass spectrometry. Muscle mitochondrial gene expression was analyzed. Results: Intramuscular total carnitine levels and short chain acylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. Intramuscular short chain acylcarnitine levels were associated with low physical performance in females, even after correction for muscle mass (%), whereas in males no such association was found. The decline in short chain acylcarnitine levels in (pre-)frail old females was associated with low expression of genes involved in mitochondrial energy production and mitochondrial functionality. Conclusions: In (pre-)frail old females, intramuscular total carnitine levels and short chain acylcarnitine levels are decreased and this decrease is accompanied by reduced physical performance and low expression of a wide range of genes involved in mitochondrial function. Overall design: A cross-sectional study was performed in well-matched fit (n = 15) and (pre-)frail (n = 13) old males as well as in fit (n = 15) and (pre-)frail (n = 11) old females, using young males (n = 13) and females (n = 13) as healthy controls. In the elderly, frailty was assessed according to the Fried criteria and physical performance was determined by 400-m walk test, short physical performance battery and handgrip strength. Acylcarnitine status was assessed in muscle biopsies and blood plasma using liquid chromatography-tandem mass spectrometry. Muscle mitochondrial gene expression was analyzed.