Neuronal rejuvenation through restoration of autophagy

Aging affects all humans and is the most critical parameter for quality and length of life.

Aging is also by far the most critical risk factor for several neurodegenerative disorders, including Parkinson’s, Alzheimer’s and Huntington’s disease.

Accumulating evidence are pointing at impairments in autophagy, a lysosomal degradation pathway, as playing a critical role in ageing and ageing related neurodegenerative diseases.

However, a clear mechanistic understanding of how autophagy declines with age and causes cellular dysfunction and neuronal death, is currently lacking.The overall aim of this study is to i) establish a cohort of fibroblasts from donors of different age ii) shed light on ageing related impairments of autophagy in neurons, ii) restore these defects for neuronal rejuvenation and iii) validate the best candidates.

This will be achieved by using models that we have recently developed specifically to study autophagy impairments in ageing and ageing related diseases.

The model is based on direct neuronal reprogramming of adult human fibroblasts that contain the ageing signature of the donor cells.

This approach will allow to tackle the vulnerability of neurons to ageing in a system that is not only of human origin but is also carrying the aging signature of the donor.This information will be instrumental to develop novel treatment strategy for ageing related diseases including Parkinson’s, Alzheimer’s disease and Huntington’s disease.