Skeletal Muscle Aging in F344BN F1-Hybrid Rats: I. Mitochondrial Dysfunction Contributes to the Age-Associated Reduction in VO2max

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Vol. 59; no. 11; pp. 1099 - 1110
• Main Authors: Hagen, Jason L., Krause, Daniel J., Baker, David J., Fu, Ming Hua, Tarnopolsky, Mark A., Hepple, Russell T.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-11-2004
• Subjects: Aerobiosis; Aging - metabolism; Animals; DNA Damage; DNA, Mitochondrial - genetics; Electron Transport; Hindlimb; Male; Mitochondria, Muscle - metabolism; Muscle Contraction; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Oxygen Consumption; Rats; Rats, Inbred BN; Rats, Inbred F344; Sequence Deletion
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/59.11.1099

Although mitochondrial DNA damage accumulates in aging skeletal muscles, how this relates to the decline in muscle mass-specific skeletal muscle aerobic function is unknown. We used a pump-perfused rat hind-limb model to examine maximal aerobic performance (V̇O2max) in young adult (YA; 8–9-month-old), late middle aged (LMA; 28–30-month-old) and senescent (SEN; 36-month-old) Fischer 344 × Brown Norway F1-hybrid rats at matched rates of convective O2 delivery (QO2). Despite similar muscle QO2 during a 4-minute contraction bout, muscle mass-specific V̇O2max was reduced in LMA (15%) and SEN (52%) versus YA. In plantaris muscle homogenates, nested polymerase chain reaction revealed an increased frequency of mitochondrial DNA deletions in the older animals. A greater reduction in the flux through electron transport chain complexes I–III than citrate synthase activity in the older animals suggests mitochondrial dysfunction consequent to mitochondrial DNA damage with aging. These results support the hypothesis that a reduced oxidative capacity, due in part to age-related mitochondrial dysfunction, contributes to the decline in aerobic performance in aging skeletal muscles.