Date Published: June 29, 2011
Publisher: Impact Journals LLC
Author(s): Michael Antosh, David Fox, Stephen L. Helfand, Leon N Cooper, Nicola Neretti.
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.
Aging is a very complex phenotype: it can assume different forms in different species, individuals, and tissues, and its mechanisms are multiple, complex and stochastic in nature. Several interventions that extend life span in many organisms have been identified, including environmental factors, genetic manipulations and drugs. It is thought that these diverse interventions share some common pathways through which they extend life span.