Abstract: 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.Keywords: Aging/*genetics/metabolism/physiology; Animals; Caenorhabditis elegans/genetics/metabolism/physiology; Cluster Analysis; *Diet; Drosophila melanogaster/genetics/metabolism/physiology; Energy Metabolism; Female; *Gene Expression Profiling; Hydrogen Peroxide/metabolism; Longevity/*genetics/physiology; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Mitochondria, Liver/genetics/metabolism/ultrastructure; Oligonucleotide Array Sequence Analysis; Peroxisomes/genetics/metabolism; RNA Interference; Reactive Oxygen Species/metabolism
Journal: Proceedings of the National Academy of Sciences of the United States of America
Date: April 18, 2012
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Zhou B, Yang L, Li S, Huang J, Chen H, Hou L, Wang J, Green CD, Yan Z, Huang X, Kaeberlein M, Zhu L, Xiao H, Liu Y, Han JD (2012) Midlife gene expressions identify modulators of aging through dietary interventions. Proceedings of the National Academy of Sciences of the United States of America 109: E1201-9.