Lessons in Aging From a Single-celled Eukaryote: Unveiling Mechanisms of Chronological Lifespan Extension in Saccharomyces Cerevisiae
Wierman, Margaret, Biochemistry and Molecular Genetics - Graduate School of Arts and Sciences, University of Virginia
Smith, Jeffrey, Biochemistry and Molecular Genetics, UVA
As an increasingly older population, aging-related diseases have become one of the largest health threats to our society. Although the pathologies vary in their specific manifestations, encompassing everything from arthritis to Alzheimer’s, research has revealed that most aging degeneration begins at the cellular level. The features of this cellular degeneration are fairly conserved across eukaryotes, and several common molecular aging pathways have been elucidated through work in model organisms. Many of these pathways were first discovered in the budding yeast, Saccharomyces cerevisiae. Through studying and identifying genetic and environmental factors that effect the chronological lifespan of yeast, specifically the amount of time a yeast cell can survive in a post-mitotic state, we too discovered novel aging factors as well as further elucidated the role of known aging pathways in mediating lifespan. A functional genomic study comparing gene expression data from several long-lived yeast populations identified several genetic biomarkers of extended chronological lifespan, revealed previously unknown genetic factors with biological aging relevance, and led to the characterization of two distinct long-lived phenotypes. One of these phenotypes is induced by caloric restriction, a nearly universal method of extending lifespan, and is characterized by the efficient consumption of alternative carbon sources. Further genetic studies revealed that this lifespan extension is mediated by several transcriptional events precipitated and sustained by the hyperactivation of Snf1. As the yeast homolog of mammalian AMPK, this finding supports the highly conserved AMPK signaling pathways as universal regulators of aging.
PHD (Doctor of Philosophy)
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