Sip2p and its partner Snf1p kinase affect aging in S-cerevisiae

For a number of organisms, the ability to withstand periods of nutrient dep rivation correlates directly with lifespan. However, the underlying molecul ar mechanisms are poorly understood. We show that deletion of the N-myristo ylprotein, Sip2p, reduces resistance to nutrient deprivation and shortens l ifespan in Saccharomyces cerevisiae. This reduced lifespan is due to accele rated aging, as defined by loss of silencing from telomeres and mating loci , nucleolar fragmentation, and accumulation of extrachromosomal rDNA. Genet ic studies indicate that sip2 Delta produces its effect on aging by increas ing the activity of Snf1p, a serine/threonine kinase involved in regulating global cellular responses to glucose starvation. Biochemical analyses reve al that as yeast age, hexokinase activity increases as does cellular ATP an d NAD(+) content. The change in glucose metabolism represents a new correla te of aging in yeast and occurs to a greater degree, and at earlier generat ional ages in sip2 Delta cells. Sip2p and Snf1p provide new molecular links between the regulation of cellular energy utilization and aging.