Comparative Genetics of Aging

Overview

Virtually every cell and tissue type displays functional decline as we age. The aging process, in turn, is influenced by a wide range of molecular and physiological processes. Determining the range of genes and molecular processes that are capable of influencing aging and understanding how they interact in the context of an aging organism is an important step to identifying key intervention points to treat age-associated disease. To this end, a primary goal of our laboratory is to identify and characterize novel genetic determinants of longevity.

We use a combination of systems and comparative genetics to study evolutionarily conserved mechanisms of aging, leveraging the unique strengths of three model organisms: humans (Homo sapiens), mice (Mus musculus), and nematodes (Caenorhabditis elegans). We employ an experimental pipeline that (1) applies systems genetics to select candidate aging gene sets in humans and mice, (2) employs longevity screening in worms to select the subset of genes capable of directly affecting longevity or other age-associated phenotypes, and (3) uses molecular tools in worms and mice to characterize selected genes and build mechanistic models describing their interaction with aging. Ultimately, we will use these models to identify molecular targets to treat age-associated disease.