No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: effects are independent of mitochondrial DNA integrity.
We investigated if calorie restriction (CR) preserved skeletal muscle oxidative capacity with aging after accounting for life span extension by CR, and determined if mitochondrial content, mitochondrial DNA integrity, and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) were involved. Ad libitum-fed (AL) and CR animals representing young adult, late middle age, and senescence were studied. Whereas citrate synthase and complex IV activities were lower in plantaris and gastrocnemius muscle of young adult CR animals, in contrast to the 15%-40% decline in senescent AL animals, there was no decline with aging in CR animals. There was no decline in citrate synthase protein in gastrocnemius with aging in either group, suggesting that CR preserves oxidative capacity with aging by protecting mitochondrial function rather than content. This protection was independent of mitochondrial DNA damage between groups. However, there was a slower decline in PGC-1alpha gene expression with aging in CR versus AL animals, suggesting a better maintenance of mitochondrial biogenesis with aging in CR animals.
Baker
David J
DJ
Faculty of Medicine, University of Calgary, Calgary, AB, T2N 1N4, Canada.
Betik
Andrew C
AC
Krause
Daniel J
DJ
Hepple
Russell T
RT
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D031204:Caloric Restriction; D004272:DNA, Mitochondrial / Q000032:analysis; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption; D047493:PPAR alpha / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344
D004272:DNA, Mitochondrial; D047493:PPAR alpha