Endocrine hormones impact aging and aging processes in multiple ways. Circulating growth hormone (GH) affects not only somatic growth but also drives many aspects of metabolism and stress resistance. We have shown that GH modulates methionine metabolism and longevity in GH mutant mice. Our current studies focus on delineating the relationships between dietary methionine, methionine metabolism and plasma GH levels as they relate to DNA methylation and potential epigenetic stability. We have conducted short and long term dietary methionine studies in GH mutant mice (Ames dwarf, GH receptor knock out, GH transgenic mice). Methionine metabolism, plasma IGF1, body weights, food consumption, end of life pathology and lifespan were examined in respective studies. Methionine conserving and catabolizing enzymes were differentially affected by dietary methionine level. Underlying GH status also influenced the metabolic responses to alterations of this amino acid. We observed that long-living GH signaling deficient (Ames, GHRKO) mice were not able to discriminate differences in dietary methionine in terms of lifespan, food consumption and body weight. GH transgenic mice and the wild type mice from each line lived longer when fed methionine-restricted but not methionine-supplemented diets. In addition, we have examined DNA methylation differences between Ames dwarf and wild type mice. The data thus far suggests that the Ames mice maintain their epigenome better (from young to old) than wild type mice supporting the notion that epigenetic stability contributes to longevity. These studies indicate that GH status affects the ability to respond to dietary methionine, and downstream aspects of metabolism including DNA methylation, health and lifespan.
Dr. Holly Brown-Borg is a Chester Fitz Distinguished Professor at the University of North Dakota.