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• W2050037370 abstract "Background Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown, and the involvement of the TOR and sirtuin pathways (which regulate aging in simpler organisms) remain controversial. Additionally, females of most mammals appear to live longer than males within species; and, although it remains unclear whether this holds true for mice, the relationship between sex-biased and CR-induced gene expression remains largely unexplored. Methodology/Principal Findings We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the sirtuin pathway. Using western analysis we confirmed post-translational inhibition of the TOR pathway. Conclusions Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of females." @default.
• W2050037370 created "2016-06-24" @default.
• W2050037370 creator A5013290989 @default.
• W2050037370 creator A5064230419 @default.
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• W2050037370 date "2009-04-16" @default.
• W2050037370 modified "2023-10-18" @default.
• W2050037370 title "Short-Term Calorie Restriction in Male Mice Feminizes Gene Expression and Alters Key Regulators of Conserved Aging Regulatory Pathways" @default.
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• W2050037370 doi "https://doi.org/10.1371/journal.pone.0005242" @default.
• W2050037370 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2667255" @default.
• W2050037370 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19370158" @default.
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