Characterization of widespread proteome aggregation through aging in mammals

Abstract

Proteome and proteostasis network disruptions accompany proteostasis alterations, leading to accumulation of protein aggregates, characteristic of several age-related diseases. Previous work in Caenorhabditis elegans and zebrafish unveiled asymptomatic protein aggregation (ARPA), characterized by generalized increased accumulation of insoluble proteins through aging. However, the consequences of protein homeostasis imbalances in the context of healthy aging in mammals remains mostly unexplored. To elucidate if accumulation of insoluble proteins also occurs through aging in mammals, C57BL/6 mice with different ages corresponding to young (6 months old), adult (13 months old), and old stages (18 and 24 months old) were used. Detergent-insoluble fractions were isolated from total protein extracts of tissues, followed by characterization of both total and detergent-insoluble protein profiles. Our results show tissue-specific proteome alterations through aging. For example, the insoluble fractions increase through aging in brain-derived tissues, but muscular tissues do not display significant alterations until 18 months old. We are now performing SWATH-MS analysis to identify differential proteome signatures of aging and which proteins are more prone to aggregate to further elucidate the functions and biological processes affected by ARPA.