The Spatiotemporal Proteome Landscape of Aging: Structural determinants of age-sensitive proteome remodeling
Abstract
Aging is marked by a decline in cellular functions accompanied by widespread changes in mRNA and protein abundance, yet whether aging broadly remodels subcellular protein localization and concentration, and why some proteins change while others remain stable, remains unclear. This gap matters because cellular function depends not only on expression levels but also on correct spatial organization. Using yeast replicative aging as a model, we built a robotic pipeline to enrich old cells from 5,661 strains, acquired 90 million single-cell 3D images, and applied machine learning to map proteome-wide changes in localization, concentration, and aggregation throughout aging. This age-resolved single-cell atlas uncovers widespread proteome remodeling and rewiring of protein interaction networks. Moreover, structural analysis reveals biophysical determinants of age-sensitive proteome remodeling across ages and species. Together, these results reveal a structure-encoded intrinsic principle underlying spatial proteome breakdown during aging and provide a resource to dissect mechanistic links among aging hallmarks. Keywords: aging, protein localization, protein concentration, protein structure.
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Research summary
The paper claims that structural determinants underlie age-sensitive proteome remodeling, revealing intrinsic principles of spatial proteome breakdown during aging. This research addresses fundamental mechanisms of aging by exploring how protein localization and concentration change, which is crucial for understanding the biological processes that contribute to aging and potential interventions.
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