Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue

Aerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS) platform. Interaction of aerobic capacity and aging was studied via regression analysis. Our results showed at young age, metabolites linked to amino acid metabolism differed in serum and muscle with aerobic capacity, whereas no difference were observed in WAT. In aged animals, most prominent changes in metabolites occurred in WAT. Aerobic capacity and aging interactively affected seven metabolites linked to energy metabolism. Our results support previous findings that high aerobic capacity is associated with more efficient amino acid metabolism in muscle. While impaired branched chain amino acids (BCAAs) and fatty acid metabolism in the muscle may associate to the high risk of metabolic disorders and shorter lifespan previously observed in LCRs. The interactive effects of aging and aerobic capacity on energy metabolism-related metabolites were largely driven by HCRs, reflecting the importance of inherited aerobic capacity in the aging process. Our results highlight that dysfunctional mitochondrial {beta}-oxidation in WAT may be one key mechanism related to aging.