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Analysis of Gene Expression and Longevity is Forging Ahead

The process of gene expression, in which a gene is used as a blueprint to construct a protein, is anything but static. Levels of gene expression for individual genes rise and fall with environmental circumstances, health, injury, and over the course of aging. It's a tremendously complex system, with a lot of feedback loops and switches, but fortunately the cost of analyzing gene expression profiles over a whole genome is falling rapidly. It is now feasible to run hundreds of such profiles over the course of a study. At the same time the tools of analysis are starting to catch up with the amount of data being generated: researchers are able to more rapidly and effectively draw conclusions from the mountainous databases they construct.

So, for example, see this study on flies, which compares groups of flies selected for their longevity versus a control group of average length lives. It demonstrates that systematically sweeping the whole genome for changes in gene expression with age is a viable way to evaluate the importance of other lines of research and find new avenues for future study:

We evaluated the gene expression profile in young, middle-aged, and old male flies, finding that 530 genes were differentially expressed between selected and control flies when measured at the same chronological age. The longevity-selected flies consistently showed expression profiles more similar to control flies one age class younger than control flies of the same age. This finding is in accordance with a younger gene expression profile in longevity-selected lines.

Among the genes down-regulated in longevity-selected lines, we found a clear over-representation of genes involved in immune functions, supporting the hypothesis of a life-shortening effect of an overactive immune system, known as inflammaging.

We judged the physiological age as the level of cumulative mortality. Eighty-four genes were differentially expressed between the control and longevity-selected lines at the same physiological age, and the overlap between the same chronological and physiological age gene lists included 40 candidate genes for increased longevity. Among these candidates were genes with roles in starvation resistance, immune response regulation, and several that have not yet been linked to longevity. Investigating these genes would provide new knowledge of the pathways that affect life span in invertebrates and, potentially, mammals.

Many research groups around the world are capable of running this sort of study. As the work shows value, more groups will do just that. We are a few years away from an avalanche of knowledge on the fine details of aging and existing differences in longevity: how it all works right down to the lowest biochemical levels in the body.

ResearchBlogging.orgSarup P, Sørensen P, & Loeschcke V (2010). Flies selected for longevity retain a young gene expression profile. Age (Dordrecht, Netherlands) PMID: 20607427

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