Cell volume as a factor limiting the replicative lifespan of the yeast Saccharomyces cerevisiae

Abstract

The number of cell divisions of the yeast Saccharomyces cerevisiae is limited, referred to as "replicative lifespan" of this organism and believed to be due to aging mechanisms similar to those of mammalian cells. We demonstrate, using three pairs of isogenic yeast strains (standard and a mutant deficient in an antioxidant defense protein) that although the lifespan differs significantly, the final volume attained after the last division is similar within each pair of strains. In a population, cells cease to bud after various number of cell cycles but attaining a similar final volume. These results indicate that the increase in the mother cell volume, intrinsic to the asymmetric cell division in S. cerevisiae, may be the main mechanism limiting the reproductive capacity of in this organism.

Cell size and growth rate are major determinants of replicative lifespan

“…Thus, the simplest model would predict that large cells are short-lived predominately because they are born In addition, several recent reports support the conclusion that increasing cell size limits lifespan. 26,27,42,43,47 Conceptually similar experiments have shown that increasing the size of human or chicken fibroblasts also shortens lifespan. 9,38 In addition, a mutation in the yeast ATP2 gene that eliminates age asymmetry (e.g., daughter cells are born old) also produces abnormally large cells.…”

“…Attempts to directly determine if increasing cell size shortens longevity have had conflicting results. 20,26,27 In order to clarify this discrepancy, we used two alternative approaches to artificially enlarge the size of long-lived ssf1Δ cells. Asynchronous log-phase cultures of ssf1Δ cells are dramatically smaller (MCV 66.6 fL) and longer-lived that was independent of birth size.…”

“…2,20,[39][40][41] Our results and the work of others have caused us to re-evaluate this conclusion. [26][27][28][42][43][44] The deletion of at least 16 single or double gene deletions that result in abnormally large cells, produce short-lived cells. [29][30][31][32]45 The possibility that abnormally large cells die young due to growth or proliferation defects is unlikely.…”

“…20 Nevertheless, since symmetric budding was only observed in very old mother cells and because increasing the size of daughter via alpha-factor treatment did not shorten lifespan, it was concluded cell size did not directly modulate lifespan. 20 However, given that recent attempts to repeat these experiments have yielded the opposite result, [26][27][28] we have re-examined the relationship between cell size and lifespan.…”

“…[26][27][28] In addition, many genes that modulate longevity also concomitantly affect cell size. For example, deletion of SCH9, RPL31a, GPA2 and many other genes reduces cell size and extends lifespan.…”