Cell enlargement drives aging-associated proteome remodeling and shortens replicative lifespan.

Feb 27, 2026bioRxiv : the preprint server for biology

Cell growth changes protein makeup and shortens cell lifespan during aging

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

The majority of aging-associated proteome changes can be replicated by genetically enlarging young yeast cells.

Cell enlargement may accelerate proteome aging and shorten replicative lifespans.
Smaller yeast cells are associated with longer lifespans.
Aging-specific molecular markers influencing lifespan were identified, though they are less prominent than cell enlargement.
Cell enlargement is a major factor affecting proteome remodeling during aging.
Established aging factors, such as extrachromosomal rDNA circles, do not influence lifespan in the same way.

AI simplified

The molecular and cellular basis of aging and its associated functional decline remains poorly understood. Even free-living microorganisms age and, in yeast, replicative aging shares key hallmarks with human cellular senescence, including progressive cell enlargement. Recent work has shown that chemical and genetic manipulations that increase cell size promote the onset of senescence in both yeast and human cells, suggesting that cell enlargement can drive some of the physiological changes associated with aging. Here, we quantitatively determined how cell enlargement contributes to age-associated physiology in yeast by combining automated aging technologies with quantitative proteomics. We find that the majority of aging-associated proteome remodeling can be recapitulated by genetically enlarging young proliferating cells. These enlarged cells exhibit accelerated proteome aging and shortened replicative lifespans, while smaller cells are longer-lived. While cell enlargement is the predominant factor driving proteome remodeling during aging, we also identified a minority of aging-specific molecular markers whose expression influences lifespan. Together, our results demonstrate that cell enlargement is a major driver of aging-associated proteome remodeling and influences lifespan independently of established aging factors such as extrachromosomal rDNA circles.

Featured in

Longevity & AgingIssue #26

Quantum sensors could detect organ aging before symptoms appear

↗

Cell enlargement drives aging-associated proteome remodeling and shortens replicative lifespan.

Abstract

Featured in

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief