Midlife gene expressions identify modulators of aging through dietary interventions

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 lifespanmodifying 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.systems biology | diet-induced obesity

A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction

“…DR is known to induce systemic changes in a whole organism (Lee et al, 1999; Pletcher et al, 2002; Zhou et al, 2012), and is therefore a good paradigm to learn how regulation of aging can be achieved at the systems level. Previously we compared the midlife liver transcriptome changes induced by caloric restriction or exercise on high-fat or low-fat diet mice, and identified molecular pathways that correlate with the mean lifespans across different regimens (Zhou et al, 2012).…”

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Identification of peculiar and common effects of histone modifications on transcription

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