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Publication : Midlife gene expressions identify modulators of aging through dietary interventions.

First Author  Zhou B Year  2012
Journal  Proc Natl Acad Sci U S A Volume  109
Issue  19 Pages  E1201-9
PubMed ID  22509016 Mgi Jnum  J:356449
Mgi Id  MGI:7762541 Doi  10.1073/pnas.1119304109
Citation  Zhou B, et al. (2012) Midlife gene expressions identify modulators of aging through dietary interventions. Proc Natl Acad Sci U S A 109(19):E1201-9
abstractText  Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. We found that pathways transcriptionally correlated with diet-modulated lifespan and physiological changes were enriched for lifespan-modifying genes. Intriguingly, mitochondrial gene expression correlated with lifespan and anticorrelated with aging-related pathological changes, whereas peroxisomal gene expression showed an opposite trend. Both organelles produce reactive oxygen species, a proposed causative factor of aging. This finding implicates a contribution of peroxisome to aging. Consistent with this hypothesis, lowering the expression levels of peroxisome proliferation genes decreased the cellular peroxide levels and extended the lifespan of Drosophila melanogaster and Caenorhabditis elegans. These findings show that transcriptional changes resulting from dietary interventions can effectively reflect causal factors in aging and identify previously unknown or under-appreciated longevity pathways, such as the peroxisome pathway.
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