Abstract

A diet known as caloric restriction is known to extend longevity of chronologically aging yeast. In studies described in this thesis, I elucidated how this longevity-extending dietary regimen influences differentiation of a population of chronologically aging yeast cells into subpopulations of quiescent and non-quiescent cells. My studies have identified two differentiation programs that define longevity of chronologically aging yeast. One of these differentiation programs progresses in yeast cultured under caloric restriction conditions, whereas another program functions in yeast not limited in calorie supply. My findings imply that each of the two differentiation programs defines longevity of chronologically aging yeast by linking cellular aging to cell cycle regulation, maintenance of a quiescent state, and entry into and progression through a non-quiescent state. I also investigated how lithocholic acid (a potent natural anti-aging compound), the pro-aging Ras family GTPase/cAMP/protein kinase A signaling pathway (one of the key regulators linking carbon source availability to cell growth and metabolism) and trehalose (a non-reducing disaccharide) regulate the two longevity-defining differentiation programs that I have discovered in studies described here. Based on my findings, here I propose a model of how lithocholic acid, the Ras family GTPase/cAMP/protein kinase A signaling pathway and trehalose define longevity of chronologically aging yeast by regulating various stages of the two differentiation programs linking cellular aging to cell cycle regulation, maintenance of a quiescent state, and entry into and progression through a non-quiescent state.