Autophagy and aging: Diet, exercise, and the link with the target of rapamycin complex 1 (TORC)
Abstract
Autophagy maintains the proteome, which is key in the aging process, as deleterious accumulation of cellular components occurs as humans advance in age. This is mediated by a decline in autophagy with age. The inhibition of autophagy precipitates degeneration and the aging phenotype while augmentation extends lifespan and delays age-related degeneration including neurodegeneration in a number of model organisms. Target of rapamycin complex 1 (TORC1), a kinase involved in protein synthesis, promotes aging and neuropathology in part by inhibiting autophagy. The inhibition of TORC1 extends lifespan through autophagy-dependent and autophagy-independent mechanisms. In neurodegenerative disease, autophagy is dysfunctional and an accrual of protein aggregates occurs leading to neuropathology. Enhancement of autophagy attenuates neurodegeneration and provides neuroprotective effects. Behavioral strategies, such as nutrition, to augment autophagy activity and promote neuroprotection and longevity are of interest. Caloric restriction and intermittent fasting may hold promise in the ability to achieve such effects.