Determining the genetic and metabolic relationship between the major longevity pathways in mammals

2012 senior Scholar Award in aging

Aging research in model organisms has revealed three major biochemical pathways that influence longevity across species. These three pathways (insulin/IGF1, AMPK, and mTOR) have the shared features that they are controlled by the nutrient status of the organism, which can likewise impact the aging process, and that they regulate local and systemic metabolism. However, the link between these pathways, as it relates to aging, is poorly understood, especially in mammals. Our project makes use of novel mouse genetic models to critically test the hypothesis that these three pathways converge to influence aging through the same mechanisms. Furthermore, we will identify shared and distinct connections between these pathways and cell, tissue, and organismal metabolism, which we believe underlie their control of the aging process and their effects on aging-related diseases. These studies will provide a deeper understanding of how dietary interventions and chemical compounds that are known to prolong lifespan in mammals exert their beneficial effects. Our ultimate goal in defining pro-longevity mechanisms is to reveal novel, and perhaps more focused, therapeutic approaches to attenuate the aging process and prevent aging-related diseases, such as cancer and diabetes.

Brendan Manning Ph.D.
Harvard School of Public Health