Scientists have long known that genetic variation contributes to differences in aging among individuals, populations, and species. Less clear are the specific genes that drive the aging process. New York University Biologist Matthew Rockman aims to uncover these genes under a $400,000 New Scholar award from the Ellison Medical Foundation.
Rockman and his colleagues will study the worm Caenorhabditis elegans (C. elegans) to understand the mechanisms by which genetic differences influence aging. C. elegans is the first animal species whose genome was completely sequenced. It is therefore a model organism for studying genetics. The NYU team will also test alternative models for the evolutionary basis of age-related genetic effects.
In conducting this research, Rockman will examine wild strains of C. elegans, which differ from one another at tens to hundreds of thousands of genetic locations. Many of these genetic differences have effects on the biology of the worms. He and his colleagues will study strains that carry random combinations of genetic variants from the wild worms and will estimate the effect of each variant on age-related traits by averaging across all the random combinations. The natural biological variation revealed by these randomizations will permit inferences about the molecular networks that connect genetic variation to variation in observable traits.
“By simultaneously tracking which worms carry which variants, we can identify the causal genes and infer whether they act directly on age-related physical attributes or whether their actions at one stage of a worm’s life indirectly influence the condition of the worm later,” Rockman explained.
Rockman added that, at the same time, the pool of genetic variants present in this population can provide insights into the evolutionary causes of aging.
“A central question in evolutionary analysis of aging is whether genetic variants that negatively influence health during aging have influences restricted to post-reproductive life or have beneficial impacts in early life,” he said. “Our systematic study of the aging gene pool in worms will allow us to analyze this question.”