Grant: Project Grant

Aging is a complex process characterized by a progressive decline of the ability of tissues to retain their functional integrity. At the cellular level, aging has been associated to a reduced capacity to maintain the integrity of the proteome (which is the ensemble of proteins present in the cell). This decline has been associated to the accumulation and aggregation (i.e., clumping) of several proteins in age-related pathologies like Alzheimer's, Parkinson's, Huntington's and prion diseases. In this project, we will specifically identify which proteins become misshapen and tend to clump in brain tissues of aging mice. Our hypothesis is that clumping proteins share similar characteristics that make them more susceptible. We will employ a computational approach to identify these features and thereby rationalize why the identified proteins are more affected upon aging. This study will lead to unique and novel fundamental knowledge that could potentially reveal how proteostasis (i.e., maintenance of a balanced proteome) is affected upon aging, and provide a first glimpse of how the cell landscape is affected when things "start to go wrong". With the current ageing society, it becomes critical that we address this knowledge gap, and identify biomarkers related to cellular aging. These age-related biomarkers could be used in the future to guide studies aiming at delaying cellular aging and stop the progression of age-related diseases.