A body of evidence supports the view that the signaling pathways governing
cellular aging - as well as mechanisms of their modulation by
longevity-extending genetic, dietary and pharmacological interventions - are
conserved across species. The scope of this review is to critically analyze
recent advances in our understanding of cell-autonomous mechanisms of
chronological aging in the budding yeast Saccharomyces
cerevisiae. Based on our analysis, we propose a concept of a
biomolecular network underlying the chronology of cellular aging in yeast. The
concept posits that such network progresses through a series of lifespan
checkpoints. At each of these checkpoints, the intracellular concentrations of
some key intermediates and products of certain metabolic pathways - as well as
the rates of coordinated flow of such metabolites within an intricate network of
intercompartmental communications - are monitored by some checkpoint-specific
ʺmaster regulatorʺ proteins. The concept envisions that a synergistic action of
these master regulator proteins at certain early-life and late-life checkpoints
modulates the rates and efficiencies of progression of such processes as cell
metabolism, growth, proliferation, stress resistance, macromolecular
homeostasis, survival and death. The concept predicts that, by modulating these
vital cellular processes throughout lifespan (i.e., prior to an arrest of cell
growth and division, and following such arrest), the checkpoint-specific master
regulator proteins orchestrate the development and maintenance of a pro- or
anti-aging cellular pattern and, thus, define longevity of chronologically aging
yeast.