Preadaptation to efficient respiratory maintenance is essential both for maximal longevity and the retention of...

Only recently have the studies of yeast ageing started to focus on the S288c-derived strains used extensively in genomics and on the longest lifespans. Chronological longevity (stationary (G(0)) survival) of such strains is greater when cells are pre-grown on a respiratory carbon source, as compared to when they are pre-grown on glucose (the latter a respiration-repressing sugar). Prior adaptation to efficient respiratory maintenance also ensures that such chronologically aged yeast cells still display a full replicative lifespan should they reenter the cell cycle. In contrast, cells that are pre-grown on glucose exhibit marked and progressive losses of replicative potential as they age chronologically in stationary phase. Increasing the respiratory activity in glucose-grown cultures by HAP4 gene overexpression increased survival and reversed the loss of replicative potential during a subsequent stationary phase. Adaptation to efficient respiratory maintenance is therefore important, not just for maximal longevity, but also for the maintenance of a full replicative lifespan by chronologically ageing cultures of yeast. In such respiration-adapted cultures, losses of the Sch9 protein kinase or Yca1 caspase both shortened lifespan. In contrast loss of Yap1, the major transcriptional regulator of the oxidative stress response, generated a small increase in chronological lifespan in certain strain backgrounds. It would appear, therefore, that any induction of oxidative stress response genes in chronologically ageing yeast is not operating to generate an increase in longevity, even though such protective effects might be expected from the increased proxidant status of these cells over time.