Overexpression of EGL-27 Extends Life in Nematodes

Many of the alterations found to extend life in lower animals like the nematode species Caenorhabditis elegans involve changes in the response to cellular stresses such as heat, starvation, and rising levels of oxidative damage due to cellular and other dysfunctions in aging. Stress response mechanisms such as increased cellular housekeeping and repair activities are important determinants of longevity in short-lived animals, but evolution has not optimized their operation for the longest possible life span. Thus a range of genetic changes can make these systems work more effectively from that perspective. Here is another example:

Stress is a fundamental aspect of aging, but it is unclear whether the molecular mechanisms underlying stress response become altered during normal aging and whether these alterations can affect the aging process. In this study, we found a GATA transcription factor called egl-27, whose targets are significantly enriched for age-dependent genes and stress response genes, and whose expression increases with age.

In contrast to previous work describing factors that are causal for aging, we found that egl-27 activity is likely beneficial for survival since egl-27 overexpression extends lifespan. egl-27 promotes longevity by enhancing stress response; specifically, increased levels of egl-27 protect animals against heat stress, while reduced egl-27 activity impairs survival following heat and oxidative stress. These results suggest that aging is not simply a process of constant decline. Some factors, such as egl-27, are more active in old animals, working to restore organismal function and to improve survival. Our work offers novel insight into the interplay between stress and aging, and suggests that aging is not simply a process of moving from an ideal young transcriptome to an inadequate old transcriptome. Rather, age-dependent changes in gene expression are likely comprised of a mix of beneficial, detrimental, and neutral changes.

Link: http://dx.doi.org/10.1371/journal.pgen.1003108


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