Autophagy in ageing and ageing-related neurodegenerative diseases

Autophagy is a catabolic mechanism that allows cells to deliver cytoplasmic contents to lysosomes for degradation to maintain energy homeostasis and to protect cells against stress. Autophagy has been directly linked to neurodegeneration and ageing by an extensive body of research. It has become evident that disruption of autophagy contributes significantly to age-related pathologies and to the cognitive and motor declines associated with “healthy” ageing. Autophagic dysfunction causes the accumulation of many of the toxic, aggregate-prone proteins that are responsible for neurodegenerative diseases, including mutant huntingtin, alpha-synuclein, tau, and others. Since upregulation of autophagy has been found to reduce levels of such protein species, the therapeutic potential of autophagy induction as a strategy against age-related diseases and a method for modulating longevity has been widely studied. Here we review the evidence supporting a role for autophagy dysfunction in the progression of the age-associated functional decline in the brain and age-related brain pathologies and discuss the available evidence that upregulation of autophagy may be a valuable therapeutic strategy.