Antosh Michael, Fox David, Helfand Stephen L, Cooper Leon N, Neretti Nicola
Department of Molecular Biology, Cell Biology and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA.
Aging (Albany NY). 2011 Jun;3(6):576-83. doi: 10.18632/aging.100342.
Environmental and genetic interventions extend health span in a range of organisms by triggering changes in different specific but complementary pathways. We investigated the gene expression changes that occur across species when health span is extended via different interventions. To perform this comparison using heterogeneous datasets from different measurement platforms and organisms, we developed a novel non-parametric methodology that can detect statistical significance of overlaps in ranked lists of genes, and estimate the number of genes with a common expression profile. By comparing genetic and environmental interventions that consistently lead to increased health span in invertebrates and vertebrates we built a conserved health span signature and described how such a signature depends on tissue type. Furthermore, we examined the relationship between calorie restriction and resveratrol administration and for the first time, identified common gene and pathway changes in calorie restriction and resveratrol in both invertebrates and mammals. Our approach can thus be used to explore and better define the relationships between highly complex biological phenomena, in this case those that affect the health and longevity.
环境和基因干预通过触发不同特定但互补途径的变化，延长了一系列生物体的健康寿命。我们研究了通过不同干预延长健康寿命时跨物种发生的基因表达变化。为了使用来自不同测量平台和生物体的异质数据集进行这种比较，我们开发了一种新颖的非参数方法，该方法可以检测基因排名列表中重叠的统计显著性，并估计具有共同表达谱的基因数量。通过比较在无脊椎动物和脊椎动物中持续导致健康寿命增加的基因和环境干预，我们构建了一个保守的健康寿命特征，并描述了这种特征如何依赖于组织类型。此外，我们研究了卡路里限制和白藜芦醇给药之间的关系，并首次确定了无脊椎动物和哺乳动物中卡路里限制和白藜芦醇的共同基因和途径变化。因此，我们的方法可用于探索和更好地定义高度复杂的生物现象之间的关系，在这种情况下，这些现象会影响健康和寿命。
