Lifelong wheel running exercise and 8% caloric restriction attenuate Caspase‐independent apoptosis via downregulation of EndoG in the Aging Fischer‐344 rat plantaris

Abstract

Aging is characterized by a progressive loss of muscle mass and muscle fiber atrophy or ¡°sarcopenia.¡ ±Although the molecular mechanisms responsible for sarcopenia have not been completely understood, recent literature indicates that mitochondrial dysfunction and apoptosis play critical roles in sarcopenia. Regular exercise and caloric restriction provide significant protection against progressive sarcopenia. We tested the hypothesis that lifelong wheel running exercise combined with mild (8%) caloric restriction (8%CR) would attenuate caspase‐independent apoptosis via downregulation of endonuclease G (EndoG) and apoptosis inducing factor (AIF) in the aging plantaris muscle. Male Fischer‐344 rats were divided into 4 groups at 11 weeks of age: ad libitum feeding until 6 mo. old (6AL, n=12); fed ad libitum until 24 mo. old (24AL, n=11); 8%CR to 24 mo of age (24CR, n=12); wheel running to 24 mo. + 8%CR (24ExCR, n=12). EndoG protein level was increased with age in both nucleosome fraction (+117%) and soluble fraction (+15%). 8%CR and wheel running exercise ameliorated age‐induced increases in EndoG in nucleosome fraction (‐37%). AIF protein level was not altered by age in both soluble and nucleosome fraction. These data indicate that lifelong wheel running and 8%CR attenuated age‐related increased in caspase‐independent apoptosis through EndoG translocation into nucleus.