Protein restriction reprograms the multi-organ proteomic landscape of mouse aging.

Abstract

Population aging is accelerating, yet the multi-organ aging process and the geroprotective effects of dietary protein restriction (PR) remain poorly understood. Here, we conducted comprehensive proteomic analyses on 41 mouse tissues during male mouse aging and PR. Our findings identified tissue-specific aging hallmarks, including widespread changes in immunoglobulins and serine protease inhibitors across multiple tissues. PR mitigated age-related tissue-specific protein expression, epigenomic states, and protein phosphorylation patterns, and it significantly improved adipose tissue functions. These findings were supported by independent reduced representation bisulfite sequencing (RRBS), phosphoproteomics, and pathological analyses. Furthermore, analysis of plasma samples from mice and humans confirmed the cardiovascular benefits of PR. We identified sexual and temporal variations in the impact of PR, with middle age being the optimal intervention period. Overall, our study depicts the multi-organ aging process and provides valuable insights into the geroprotective potential of PR.