Abstract
Increasing genomic instability is associated with aging in eukaryotes, but the connection between genomic instability and natural variation in life span is unknown. We have quantified chronological life span and loss-of-heterozygosity (LOH) in 11 natural isolates of Saccharomyces cerevisiae. We show that genomic instability increases and mitotic asymmetry breaks down during chronological aging. The age-dependent increase of genomic instability generally lags behind the drop of viability and this delay accounts for ∼50% of the observed natural variation of replicative life span in these yeast isolates. We conclude that the abilities of yeast strains to tolerate genomic instability co-vary with their replicative life spans. To the best of our knowledge, this is the first quantitative evidence that demonstrates a link between genomic instability and natural variation in life span.
Highlights
Accumulation of oxidative damage and loss of genomic integrity likely contribute to the finite life spans of organisms from yeast to humans
Ability of natural isolates to tolerate genomic instability during chronological aging co-varies with replicative life spans Above we showed a striking increase in genomic instability as measured by LOH during chronological aging in both mother cells, indicated by the full-black colonies, and the daughter cells, indicated by the half-black colonies
We provide the first quantitative study on genomic instability and natural life span variation and we report a striking increase in genomic instability during chronological aging in the form of LOH in both mother and daughter cells
Summary
Accumulation of oxidative damage and loss of genomic integrity likely contribute to the finite life spans of organisms from yeast to humans. Daughter cells of aging mother cells are generally born rejuvenated due, in part, to the partition of damaged proteins to mother cells [7]. This mitotic asymmetry breaks down in very old mother cells [8]. Daughter cells of older mother cells are relatively shorter-lived than those of younger mother cells [9] and their genomes become increasingly unstable, as measured by lossof-heterozygosity (LOH) [10,11]. Mutations that disrupt mitotic asymmetry are known to shorten the replicative life spans of both mother and daughter cells [7,12]
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