Aging skeletal muscle mitochondria in the rat: decreased uncoupling protein-3 content.
The goal of the present study was to discern the cellular mechanism(s) that contributes to the age-associated decrease in skeletal muscle aerobic capacity. Skeletal muscle mitochondrial content, a parameter of oxidative capacity, was significantly lower (25 and 20% calculated on the basis of citrate synthase and succinate dehydrogenase activities, respectively) in 24-mo-old Fischer 344 rats compared with 6-mo-old adult rats. Mitochondria isolated from skeletal muscle of both age groups had identical state 3 (ADP-stimulated) and ADP-stimulated maximal respiratory rates and phosphorylation potential (ADP-to-O ratios) with both nonlipid and lipid substrates. In contrast, mitochondria from 24-mo-old rats displayed significantly lower state 4 (ADP-limited) respiratory rates and, consequently, higher respiratory control ratios. Consistent with the tighter coupling, there was a 68% reduction in uncoupling protein-3 (UCP-3) abundance in mitochondria from elderly compared with adult rats. Congruent with the respiratory studies, there was no age-associated decrease in carnitine palmitoyltransferase I and carnitine palmitoyltransferase II activities in isolated skeletal muscle mitochondria. However, there was a small, significant decrease in tissue total carnitine content. It is concluded that the in vivo observed decrease in skeletal muscle aerobic capacity with advanced age is a consequence of the decreased mitochondrial density. On the basis of the dramatic reduction of UCP-3 content associated with decreased state 4 respiration of skeletal muscle mitochondria from elderly rats, we propose that an increased free radical production might contribute to the metabolic compromise in aging.
Kerner
J
J
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106, USA. jxk81@po.cwru.edu
Turkaly
P J
PJ
Minkler
P E
PE
Hoppel
C L
CL
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000375:Aging; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D007473:Ion Channels; D007700:Kinetics; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D013385:Succinate Dehydrogenase / Q000378:metabolism; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D000244:Adenosine Diphosphate; D013385:Succinate Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase