title: Time line of redox events in aging postmitotic cells.
abstract: The precise roles that oxidants play in lifespan and aging are still unknown. Here, we report the discovery that chronologically aging yeast cells undergo a sudden redox collapse, which affects over 80% of identified thiol-containing proteins. We present evidence that this redox collapse is not triggered by an increase in endogenous oxidants as would have been postulated by the free radical theory of aging. Instead it appears to be instigated by a substantial drop in cellular NADPH, which normally provides the electron source for maintaining cellular redox homeostasis. This decrease in NADPH levels occurs very early during lifespan and sets into motion a cascade that is predicted to down-regulate most cellular processes. Caloric restriction, a near-universal lifespan extending measure, increases NADPH levels and delays each facet of the cascade. Our studies reveal a time line of events leading up to the system-wide oxidation of the proteome days before cell death.DOI:http://dx.doi.org/10.7554/eLife.00306.001.
authors: Department of Molecular, Cellular, and Developmental Biology ,  University of Michigan ,  Ann Arbor ,  United States.
authors: Nicolas
authors: N
authors: Brandes
authors: Heather
authors: H
authors: Tienson
authors: Antje
authors: A
authors: Lindemann
authors: Victor
authors: V
authors: Vitvitsky
authors: Dana
authors: D
authors: Reichmann
authors: Ruma
authors: R
authors: Banerjee
authors: Ursula
authors: U
authors: Jakob
mesh_terms: D000375:Aging / Q000378:metabolism; D016000:Cluster Analysis; D015536:Down-Regulation; D006706:Homeostasis; D008938:Mitosis; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020543:Proteome; D040901:Proteomics / Q000379:methods; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013997:Time Factors
chemical_list: D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; D009249:NADP; D013880:Thioredoxin-Disulfide Reductase
keywords: Aging; Metabolism; Oxidative Stress; Redox Proteomics; Redox Regulation; S. cerevisiae
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