Growing Old Together: Yeast, Worms, And People May Age By Similar Mechanisms
While nearly all organisms experience aging, the underlying mechanisms have eluded geneticists and evolutionary biologists. Many different theories have been suggested, yet experimental evidence strongly suggests that aging is modulated, at least in part, by genetic factors. Previous studies have implicated a number of conserved genes in model organisms as regulators of aging, such as the Sirtuins and insulin/IGF1 receptors. However, no investigations to date have quantified the degree to which aging-related genes are conserved across the genome among distantly related species.
In the study published today, a group of researchers led by Drs. Matt Kaeberlein and Brian Kennedy of the University of Washington conducted a genome-wide analysis of the yeast Saccharomyces cerevisiae and the nematode worm Caenorhabditis elegans, to identify genes that may regulate aging in humans. "Nematodes and humans are more similar to each other on an evolutionary scale than nematodes and yeast," explains Dr. Erica Smith, primary author of the study. "We reasoned that if a particular gene modulates aging in both yeast and nematodes, there is a good chance that gene plays a similar role in people."
The researchers compiled a set of 276 C. elegans genes that were known to modulate aging, and scanned the yeast genome for genes with highly similar sequences. The highly similar yeast genes were then individually analyzed for a potential role in longevity by measuring the life span of yeast cells lacking each gene. "Our study identified 25 genes that regulate aging in both yeast and nematodes, 22 of which were not previously known to be conserved modulators of aging," says Kaeberlein. As 15 of the 25 yeast genes are highly similar to known human genes, Kaeberlein adds that this work is readily applicable to human aging research. "It is reasonable to speculate that many of the genes identified in our study also regulate longevity in humans."
In addition to identifying related pairs of aging-associated genes in yeast and nematodes, the group also investigated whether these genes are involved in common functional pathways. "We find that there is significant overlap between nematode and yeast aging genes, particularly those in nutrient-response pathways," describes Kennedy. Signaling pathways involved in the response to nutrients have previously been implicated in the regulation of aging. "This finding indicates that two very different species age through overlapping mechanisms and suggests that these mechanisms are likely to also contribute to human aging."
The genes identified in this study now provide a foundation for extending this research to a higher model organism, and ultimately for understanding human aging. "It will be important to determine how each of these genes modulate aging at the molecular level, and to test whether they also modulate aging in a mammalian model, such as mice," says Kaeberlein. "In principle, any of these genes could be a useful therapeutic target for treating age-associated diseases."
Scientists from the University of Washington (Seattle, WA) and the University of Georgia (Athens, GA) contributed to this study.
This work was supported by grants from the Ellison Medical Foundation and the National Institutes of Health.
"Quantitative evidence for conserved longevity pathways between divergent eukaryotic species."
Smith, E.D., Tsuchiya, M., Fox, L.A., Dang, N., Hu, D., Kerr, E.O., Johnston, E.D., Tchao, B.N., Pak, D.N., Welton, K.L., Promislow., D.E.L., Thomas, J.H., Kaeberlein, M., and Kennedy, B.K.
Genome Res. doi:10.1101/gr.074724.107.
About Genome Research
Genome Research is an international, continuously published, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics. Genome Research
About Cold Spring Harbor Laboratory Press
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Dezvoltãm împreunã veche: drojdie, viermi, ºi de cãtre persoane pot vârstã similar de mecanisme - Growing Old Together: Yeast, Worms, And People May Age By Similar Mechanisms - articole medicale engleza - startsanatate