Mitochondrial Function and mtDNA Deletions in Sarcopenia

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DESCRIPTION (provided by applicant): There is evidence that age-related deletions in mitochondrial DNA (mtDNA) secondary to increased oxidative stress and/or decreased antioxidant defense reach a critical threshold, resulting in cellular damage and ultimately the loss of muscle mass and function. We propose to determine if the non-invasive in vivo measure of mitochondrial function by 31Phosphorus magnetic resonance spectroscopy (31P MRS), is correlated to in vitro (biopsy) measures of mitochondrial function and mitochondrial DNA deletions (mtDNA), and to investigate the relationships between long-term physical function/physical activity, and nutritional/supplement intake with these measures in sarcopenic and non-sarcopenic elderly. We hypothesize that older sarcopenic adults will be more frail physically and display significantly more evidence of mitochondrial dysfunction and mtDNA deletions compared to age-and sex-matched non- sarcopenic elderly. This proposal will utilize a novel, multi-disciplinary approach using an in vivo measure of muscle mitochondrial function (31P MRS), and in vitro biopsy measures of mitochondrial function (Complex I and IV activities and mtDNA deletions to better define relationships between sarcopenia, mitochondrial function, and mtDNA deletions. Twenty-eight healthy non-sarcopenic, and sarcopenic elderly subjects will have a dynamic 31P MRS test (mitochondrial function) and a skeletal muscle biopsy in the same muscle to determine mitochondrial function (Complex I and IV activities) and mtDNA deletions. Five -ten years of existing longitudinal data on physical activity, physical function, nutrition, and vitamin/supplement intake and these measures will be investigated for associated relationships. As sarcopenia is related to increasing disability in the elderly, the translation of these findings to controlled trials of novel interventions with clinical outcomes, will allow us to begin to uncover the precise mechanisms by which different therapies may lead to better identification of aging adults at risk, and improved approaches for the prevention or reversal of sarcopenia.