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• W2056845036 startingPage "e69178" @default.
• W2056845036 abstract "There is increasing evidence that nutrient-sensing machinery is critically involved in the regulation of aging. The insulin/insulin-like growth factor-1 signaling pathway is the best-characterized pathway with an influence on longevity in a variety of organisms, ranging from yeast to rodents. Reduced expression of the receptor for this pathway has been reported to prolong the lifespan; however, the underlying mechanisms are largely unknown. Here we show that haploinsufficiency of Akt1 leads to an increase of the lifespan in mice. Akt1+/– mice had a lower body weight than their littermates with less fat mass and normal glucose metabolism. Ribosomal biogenesis and the mitochondrial DNA content were significantly reduced in these mice, along with a decrease of oxidative stress. Consistent with the results obtained in mice, inhibition of Akt-1 promoted longevity in nematodes (Caenorhabditis elegans), whereas activation of Akt-1 shortened the lifespan. Inhibition of Akt-1 led to a decrease of ribosomal gene expression and the mitochondrial DNA content in both human cells and nematodes. Moreover, deletion of ribosomal gene expression resulted in a decrease of the mitochondrial DNA content and normalized the lifespan shortened by Akt-1 activation in nematodes. These results suggest that an increase of mitochondrial amount and energy expenditure associated with enhanced protein synthesis accelerates both aging and the onset of age-associated diseases." @default.
• W2056845036 created "2016-06-24" @default.
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• W2056845036 date "2013-07-30" @default.
• W2056845036 modified "2023-10-17" @default.
• W2056845036 title "Haploinsufficiency of Akt1 Prolongs the Lifespan of Mice" @default.
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• W2056845036 doi "https://doi.org/10.1371/journal.pone.0069178" @default.
• W2056845036 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3728301" @default.
• W2056845036 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23935948" @default.
• W2056845036 hasPublicationYear "2013" @default.
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