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The Spatiotemporal Proteome Landscape of Aging: Structural determinants of age-sensitive proteome remodeling

Yoo, S.; Vannur, L.; Li, L.; Young, C.; Liu, Q.; Wen, Z.; Zhang, Y.; Florens, L.; Si, K.; Zhuang, J.; Zheng, F.; Zhou, C.

2026-03-01 systems biology
10.64898/2026.02.26.708310 bioRxiv
Show 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.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.