It was recently reported that Sir2 protein levels decline in aging haploid cells after only 7-9 generations, a relatively early point in their life span [36]. Our findings are consistent with this earlier work: Sir2 protein levels in aging diploid cells show a precipitous decline by 24 hours. However, this occurs at a time in which LOH rates have not yet increased and ∼95% of cells remain viable. Furthermore, when Sir2 was over expressed, no suppression of age-associated LOH rates was observed. Taking all these results together, we interpret these data to indicate that declining Sir2 protein levels do not correlate with the increase in age-associated LOH and offer further evidence that Sir2 is unlikely to be responsible for the age-associated increase in LOH. One potential caveat to our interpretation is that if there is significant cell-to-cell heterogeneity in levels of Sir2 over-expression, then LOH may occur in a subpopulation of cells with lower Sir2 levels.
