title: Early manifestations of replicative aging in the yeastSaccharomyces cerevisiae.
abstract: The yeastSaccharomyces cerevisiaeis successfully used as a model organism to find genes responsible for lifespan control of higher organisms. As functional decline of higher eukaryotes can start as early as one quarter of the average lifespan, we asked whetherS. cerevisiaecan be used to model this manifestation of aging. While the average replicative lifespan ofS. cerevisiaemother cells ranges between 15 and 30 division cycles, we found that resistances to certain stresses start to decrease much earlier. Looking into the mechanism, we found that knockouts of genes responsible for mitochondria-to-nucleus (retrograde) signaling,RTG1orRTG3,significantly decrease the resistance of cells that generated more than four daughters, but not of the younger ones. We also found that even young mother cells frequently contain mitochondria with heterogeneous transmembrane potential and that the percentage of such cells correlates with replicative age. Together, these facts suggest that retrograde signaling starts to malfunction in relatively young cells, leading to accumulation of heterogeneous mitochondria within one cell. The latter may further contribute to a decline in stress resistances.
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Moscow State University, Vorobyevy Gory 1, Moscow, Russia. ; Institute of Mitoengineering, Moscow State University, Vorobyevy Gory 1, Moscow, Russia.
authors.forename: Maksim I
authors.initials: MI
authors.lastname: Sorokin
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Moscow, Russia. ; Institute of Mitoengineering, Moscow State University, Vorobyevy Gory 1, Moscow, Russia.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Knorre
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Moscow, Russia. ; Institute of Mitoengineering, Moscow State University, Vorobyevy Gory 1, Moscow, Russia.
authors.forename: Fedor F
authors.initials: FF
authors.lastname: Severin
keywords: aging; retrograde signaling; stress resistance; yeast