Cell Cycle Regulation of Replicative Life Span

By: Joe Delaney

Dietary restriction has been shown to extend life span in a manner which is dependent on the transcription factor Gcn4.  Mutants in ribosomal biogenesis are also able to extend lifespan in a Gcn4 dependent manner.  We have previously shown that many long lived mutants, including these ribosome biogenesis mutants, delay in the G1 phase of the cell cycle.  We formed the hypothesis that this G1 delay is important for lifespan extension.  To test this hypothesis, we are utilizing the deletion mutant of WHI5, which is the primary regulator of G1/s phase transition.  Without Whi5, cells progress into S phase much sooner, which abrogates the G1 delay.  We are testing if this annulment of the G1 delay also shortens the long life span of G1 delayed mutants.  Once this question is answered, we also hope to ascertain what transcriptional programs are activated during the G1 phase of the cell cycle which may be causal for life span extension.