Academic Interests
Our laboratory is exploring the genetic control of aging in mammals and endocrine mechanisms responsible for the effects of longevity genes. We reported the first evidence that mutation of a single gene can significantly extend lifespan in a mammal, and have extensively characterized the phenotype of long-lived Ames dwarf (Prop1df) mice, identifying several mechanisms that are likely to explain or contribute to their delayed aging and greatly prolonged longevity. We have performed similar studies of long-lived growth hormone receptor knockout (GHR-KO or “Laron dwarf”) mice and demonstrated numerous similarities in the characteristics related to aging and longevity in the two mutant animals. Our findings, along with results from other laboratories, firmly establish the physiological role of the somatotropic axis (GH and IGF-1) in the control of aging in mammals.
We are also examining interactions of mouse longevity genes with calorie restriction. We have demonstrated that a 30% dietary reduction leads to further, significant extension of the average and maximal lifespan in Ames dwarf mice, but has little if any effect on the longevity of GHR-KO animals. Studies of the expression of genes related to GH, IGF-1 and insulin signaling, as well as analysis of broad profiles of gene expression, suggest that Prop1df and GHR-KO animals have prolonged lives by mechanisms that are overlapping but definitely not identical to the effects of caloric restriction.