Overview of Research Interests
Mechanisms of Aging
Determining the pathways and mechanisms that hormones utilize may suggest potential therapeutic interventions that could lead to strategies to delay aging, treat aging-related disorders and extend life span in humans. The somatotropic axis plays a major role in aging and longevity. Mice with hereditary dwarfism (Ames dwarf, df/df) and growth hormone (GH) deficiency exhibit delayed aging, living 49-68% longer (males and females, respectively) than normal siblings and differences in their antioxidant defense capacity, mitochondrial function, metabolism, stress resistance and DNA methylation patterns. In contrast, mice with high plasma GH concentrations live half as long as normal, wild type siblings and exhibit depressed antioxidative defense capacity and reduced stress resistance. The overall hypothesis is that reduced somatotropic signaling confers a biologic advantage (increased health span and delayed aging) to mammals with better enzymatic scavenging of toxic metabolic byproducts, less mitochondrial membrane leakage, and enhanced stress resistance. Our current studies are designed to understand the relationship between cellular metabolism, hormones, mitochondrial activities and aging in various mouse strains of extended and shortened life spans. The epigenetic signature of long-living mice also differs from normal animals in terms of DNA methylation patterns and the underlying mechanisms that promote methylation. We are investigating the interplay between hormone levels, methylation and gene expression in terms of aging and age-related disease.