Extrachromosomal rDNA circles--a cause of aging in yeast.
Although many cellular and organismal changes have been described in aging individuals, a precise, molecular cause of aging has yet to be found. A prior study of aging yeast mother cells showed a progressive enlargement and fragmentation of the nucleolus. Here we show that these nucleolar changes are likely due to the accumulation of extrachromosomal rDNA circles (ERCs) in old cells and that, in fact, ERCs cause aging. Mutants for sgs1, the yeast homolog of the Werner's syndrome gene, accumulate ERCs more rapidly, leading to premature aging and a shorter life span. We speculate on the generality of this molecular cause of aging in higher species, including mammals.
Sinclair
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DA
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Guarente
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D000375:Aging / Q000235:genetics; D002466:Cell Nucleolus / Q000737:chemistry; D016922:Cellular Senescence; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology; D004270:DNA, Circular / Q000235:genetics / Q000502:physiology*; D004271:DNA, Fungal / Q000235:genetics / Q000502:physiology*; D004275:DNA, Ribosomal / Q000235:genetics / Q000502:physiology*; D053484:RecQ Helicases; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D015003:Yeasts / Q000235:genetics* / Q000502:physiology
D004270:DNA, Circular; D004271:DNA, Fungal; D004275:DNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; C090472:SGS1 protein, S cerevisiae; D004265:DNA Helicases; D053484:RecQ Helicases