TARGETING SELECTIVE AUTOPHAGY AGAINST PROTEOTOXICITY IN AGING AND AGE-RELATED DISEASES

Autophagy is an important component of the proteostasis networks that assure maintenance of a healthy proteome in all our cells. Autophagy malfunction is a common feature in aging organism and in many severe age-related diseases such as neurogenerative conditions. The several autophagic systems that co-exist in most cells are affected in a different manner by age. We have identified the molecular defect in a form of selective autophagy responsible for its diminished activity in aging. Genetic approaches to mimic this defect in young organism have revealed organ-specific changes in proteostasis and different degrees of proteotoxicity, that depend on the ability of each tissue to compensate for the autophagic failure. In this talk I will discuss our current efforts to prevent the decline or to restore normal selective autophagic activity using genetic and chemical interventions and the impact that these manipulations have in physiological aging and in neurodegenerative conditions.