Skeletal muscle aging in F344BN F1-hybrid rats: I. Mitochondrial dysfunction contributes to the age-associated reduction in VO2max.
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 (VO(2max)) in young adult (YA; 8-9-month-old), late middle aged (LMA; 28-30-month-old) and senescent (SEN; 36-month-old) Fischer 344 x Brown Norway F1-hybrid rats at matched rates of convective O(2) delivery (QO(2)). Despite similar muscle QO(2) during a 4-minute contraction bout, muscle mass-specific VO(2max) 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.
Hagen
Jason L
JL
Faculty of Kinesiology, University of Calgary, 2500 University Dr. NW, Calgary, AB, Canada T2N 1N4.
Krause
Daniel J
DJ
Baker
David J
DJ
Fu
Ming Hua
MH
Tarnopolsky
Mark A
MA
Hepple
Russell T
RT
D000332:Aerobiosis; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics; D004579:Electron Transport; D006614:Hindlimb; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000502:physiology; D010101:Oxygen Consumption; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017384:Sequence Deletion
D004272:DNA, Mitochondrial