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M olecular G enetics of   A ging

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Aging is a fundamental mystery in biology. Although a number of genetic and environmental factors that affect aging have been discovered, the mechanisms by which these factors influence aging are poorly understood. This is mainly due to the difficulty in studying complex aging processes at the organismal level. The roundworm C. elegans is an excellent model animal to overcome these complications because of its genetic tractability, ease of culture in controlled environments and very short lifespan. In our laboratory we have been elucidating the molecular mechanisms by which these genetic and environmental factors regulate lifespan using C. elegans as a main model organism.

1. How can we dissect complex interactions between genetic and environmental factors that affect aging?

We are working on how two important environmental factors, glucose-enriched diets and food cues, influence the lifespan of C. elegans. Our findings suggest that the effects on lifespan of both diets rich in glucose and food-derived cues act through endocrine signaling pathways. Our discoveries represent novel departures from previously existing beliefs about how these two factors influence longevity. We are currently further investigating the interactions between each of these environmental factors and the endocrine signaling pathways that regulate lifespan.

2. What are the genes that regulate lifespan in response to environmental changes?

Despite the generally accepted notion that environmental factors can influence lifespan, the identification of genes that mediate such effects remain incomplete. Therefore, we have been conducting large scale gene discovery efforts by employing RNA sequencing analysis, RNAi screening and chemical mutagenesis screening. We will determine the functional significance of candidate genes obtained from these experiments and mechanistically characterize these genes.

3. Are our findings in C. elegans conserved in vertebrates?

One important long-term goal of aging research using C. elegans is to provide more information to help understand general aging processes including those of human aging. Therefore, we plan to test whether our findings in C. elegans are conserved in other complex organisms. Currently, our laboratory is setting up a vertebrate model to address this quest.

Because many findings regarding the regulation of aging in C. elegans have already been shown to be amazingly well conserved in other species, including mammals, we believe our research will eventually help us understand the secrets of human aging and improve the quality of old age.