Abstract
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.
Highlights
The budding yeast S. cerevisiae is an advantageous model organism for unveiling fundamental mechanisms and biological principles underlying the inherent complexity of cellular aging in multicellular eukaryotes [1,2,3,4,5,6]
Emergent evidence supports the view that the processes of cell metabolism, growth, proliferation, stress resistance, macromolecular homeostasis, survival and death in chronologically aging yeast are integrated into a biomolecular network of cellular aging
Recent findings imply that a stepwise progression of this network through a series of the early-life and late-life checkpoints is monitored by some checkpoint-specific master regulator proteins; these proteins act in synergy to orchestrate the development and maintenance of a pro- or anti-aging cellular pattern and, to define longevity of chronologically aging yeast
Summary
The budding yeast S. cerevisiae is an advantageous model organism for unveiling fundamental mechanisms and biological principles underlying the inherent complexity of cellular aging in multicellular eukaryotes [1,2,3,4,5,6].
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