Abstract：
:Although genetic mutations that alter organisms' average lifespans have been identified in aging research, our understanding of the dynamic changes during aging remains limited. Here, we integrate single-cell imaging, microfluidics, and computational modeling to investigate phenotypic divergence and cellular heterogeneity during replicative aging of single S. cerevisiae cells. Specifically, we find that isogenic cells diverge early in life toward one of two aging paths, which are characterized by distinct age-associated phenotypes. We captured the dynamics of single cells along the paths with a stochastic discrete-state model, which accurately predicts both the measured heterogeneity and the lifespan of cells on each path within a cell population. Our analysis suggests that genetic and environmental factors influence both a cell's choice of paths and the kinetics of paths themselves. Given that these factors are highly conserved throughout eukaryotes, divergent aging might represent a general scheme in cellular aging of other organisms.
journal_name
Cell Systjournal_title
Cell systemsauthors
Jin M,Li Y,O'Laughlin R,Bittihn P,Pillus L,Tsimring LS,Hasty J,Hao Ndoi
10.1016/j.cels.2019.02.002subject
Has Abstractpub_date
2019-03-27 00:00:00pages
242-253.e3issue
3eissn
2405-4712issn
2405-4720pii
S2405-4712(19)30036-5journal_volume
8pub_type
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