Skeletal muscle autophagy and apoptosis during aging: Effects of calorie restriction and life-long exercise

Potential mechanisms for these changes include age-related declines in proteasome activity, ubiquitylation and autophagy deficiencies, and impaired removal of degraded proteins and end products.

“Potential mechanisms explaining these changes include age-related reductions in protea some activity, deficiencies in ubiquitylation and autophagy and impairments in removing degraded proteins and end products82–84.”

Lipotoxicity impairs muscle fibre contractility and interferes with muscle protein synthesis, worsening sarcopenia.

“This lipotoxicity impairs muscle fibre contractility and interferes with muscle protein synthesis, exacerbating sarcopenia82–84.”

Exercise reduces apoptosis and increases mitophagy.

“We know that exercise downregulates apoptosis and upregulates mitophagy (4, 52, 128, 146).”

CR reduces markers of apoptosis in aged rat skeletal muscle.

“CR has also been shown to reduce markers of apoptosis in aged rat skeletal muscle (Wohlgemuth et al., 2010).”

In healthy cells, autophagy is essential for the removal of damaged or energy-deficient mitochondria that would otherwise accumulate and induce mitochondrion-mediated cell death.

“In healthy cells, autophagy is essential for the removal of damaged or energy-deficient mitochondria that would otherwise accumulate and induce mitochondrion-mediated cell death (Wohlgemuth et al., 2010).”

Reduced lysosomal degradation capacity and autophagy have been reported in aged hepatocytes and in skeletal muscle from aged Fischer 344 rats.

“Indeed, reduced lysosomal degradation capacity and autophagy have been reported in aged hepatocytes (Donati et al., 2001; Terman, 1995) and, more recently, have been observed in skeletal muscle from aged Fischer 344 rats (Wohlgemuth et al., 2010).”

Autophagy is negatively correlated with oxidative damage and apoptosis in skeletal muscle from aged rodents.

“This idea is further corroborated by results of a recent study demonstrating that autophagy is negatively correlated with oxidative damage and apoptosis in skeletal muscle from aged rodents (Wohlgemuth et al., 2010).”

The lysosomal-autophagy system declines in a variety of tissues with age.

“Although there is conflicting evidence regarding the effect of aging on various proteolytic pathways (for reviews, see Attaix et al., 2005; Combaret et al., 2009), it has been reported that the lysosomal-autophagy system declines in a variety of tissues with age (Cuervo and Dice, 2000; Donati et al., 2001; Wohlgemuth et al., 2010).”

Exercise training restores age-associated deficits in autophagy, which translates into effective removal of damaged and dysfunctional organelles, including mitochondria.

“Moreover, exercise training restores age-associated deficits in autophagy (22), which translates into effective removal of damaged and dysfunctional organelles, including mitochondria.”