Mukesh K. Jain, MD

Dean of Medicine and Biological Sciences

Frank L. Day Professor of Biology

Aging and age-associated disorders constitute some of the greatest unmet medical challenges facing society today. Current paradigms suggest that dysfunction of the immune and metabolic systems contribute to aging and age-associated disorders, but the molecular underpinnings controlling these processes remain incompletely understood. Our work has identified a family of genetic factors termed Krüppel-like factors (KLFs) as nodal regulators of immunity and metabolism. Studies in C. elegans demonstrate that KLFs are necessary and sufficient to control lifespan and healthspan. Mammalian studies demonstrate an essential role for KLFs in immunometabolism and the development of age-associated metabolic, cardiovascular, and neurocognitive dysfunction. Collectively these findings support an essential role for KLFs in aging and age-related disorders across metazoan phylogeny. Here these insights will be reviewed and therapeutic implications discussed.