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Genes & Dev. 14 (15): 1872-1885

Copyright © 2000 by Cold Spring Harbor Laboratory Press.

Vol. 14, No. 15, pp. 1872-1885, August 1, 2000

RESEARCH PAPER
Sip2p and its partner Snf1p kinase affect aging in S. cerevisiae

Kaveh Ashrafi, Stephen S. Lin, Jill K. Manchester, and Jeffrey I. Gordon1

Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110 USA

For a number of organisms, the ability to withstand periods of nutrient deprivation correlates directly with lifespan. However, the underlying molecular mechanisms are poorly understood. We show that deletion of the N-myristoylprotein, Sip2p, reduces resistance to nutrient deprivation and shortens lifespan in Saccharomyces cerevisiae. This reduced lifespan is due to accelerated aging, as defined by loss of silencing from telomeres and mating loci, nucleolar fragmentation, and accumulation of extrachromosomal rDNA. Genetic studies indicate that sip2Delta produces its effect on aging by increasing the activity of Snf1p, a serine/threonine kinase involved in regulating global cellular responses to glucose starvation. Biochemical analyses reveal that as yeast age, hexokinase activity increases as does cellular ATP and NAD+ content. The change in glucose metabolism represents a new correlate of aging in yeast and occurs to a greater degree, and at earlier generational ages in sip2Delta cells. Sip2p and Snf1p provide new molecular links between the regulation of cellular energy utilization and aging.

[Key Words: Aging; Saccharomyces cervisiae; N-myristoylproteins; Snf1p kinase interacting protein-2; glucose metabolism; cellular energy storage]


1 Corresponding author.


GENES & DEVELOPMENT 14:1872-1885 © 2000 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/00 $5.00

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