A comprehensive multi-organ proteomic atlas of human aging across 50 years

Multi-organ map of aging by proteomicsAging leads to a progressive decline in tissue function and structure across all organ systems, underlying the risk of various chronic diseases. 1 Although studies in animals have shown that different organs have distinct aging rates, the molecular trajectories of aging across different human organs remain largely unexplored. 2 In a recent landmark study, Ding and colleagues constructed the most comprehensive proteomic atlas of human aging, profiling over 12,771 proteins in 516 samples across 13 tissues from donors aged 14 to 68. 3 This extensive dataset of diverse organs, such as heart, lung, liver, spleen, muscle, intestine, skin, and blood vessels, provides an unprecedented "proteome blueprint" of the dynamic aging process of our organs over five decades (Figure 1).Using state-of-the-art mass spectrometry, Ding et al. quantified thousands of proteins per tissue and paired this with transcriptomics data from the same sample.An interesting finding was a widespread dissociation between mRNA and protein expression during the aging process.This transcriptome-proteome decoupling phenomena has also been identified by many studies in individual human organ. [4]5][6] The decoupling identified in various human organ suggests that aged tissue starts to lose control over translating original genetic information into functional proteins.Notably, many proteins critical for fundamental tissue maintenance showed this decoupling in aged tissues (for example, proteins regulating B-cell activation in the spleen), underscoring that the proteomic level of aging should be directly examined, rather than only at the transcriptomics level.This finding aligns with the decline in proteostasis observed during aging, including decreased levels of protein synthesis machinery (ribosomal proteins and tRNA synthetases).