Chinese Academy of Sciences Key Laboratory for Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Proc Natl Acad Sci U S A. 2012 May 8;109(19):E1201-9. doi: 10.1073/pnas.1119304109. Epub 2012 Apr 16.
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.
饮食干预是延长或缩短寿命的有效方法。通过检查不同饮食条件下小鼠中年期肝脏的基因表达，这些饮食条件导致了不同的寿命和与衰老相关的表型，我们能够鉴定出调节衰老过程的基因和途径。我们发现，与饮食调节寿命和生理变化转录相关的途径富含寿命修饰基因。有趣的是，线粒体基因表达与寿命相关，与与衰老相关的病理变化呈负相关，而过氧化物酶体基因表达则呈现相反的趋势。这两个细胞器都产生活性氧，这是衰老的一个潜在原因。这一发现暗示了过氧化物酶体对衰老的贡献。与这一假设一致的是，降低过氧化物酶体增殖基因的表达水平降低了细胞内的过氧化物水平，并延长了黑腹果蝇和秀丽隐杆线虫的寿命。这些发现表明，饮食干预引起的转录变化可以有效地反映衰老的因果因素，并确定以前未知或被低估的长寿途径，如过氧化物酶体途径。
