About Dr. Michal Masternak’s Work
The goal of our laboratory is to study the genetic mechanism in mutant mice that help them to live much longer than their normal littermates. Our current research is focused on relating somatotropic and insulin signaling to metabolic alterations in adipose tissue and their effects on longevity and aging.
It was previously reported that mutation of a single gene can significantly extend lifespan in Ames dwarf mice. There was similar life extension in growth hormone receptor knockout (GHRKO or “Laron dwarf”) mice produced by Zhou et al. in the laboratory of Dr. John Kopchick. These results, along with results from other laboratories, firmly establish the physiological role of the somatotropic axis (growth hormone and IGF-1) in the control of aging in mammals.
Studies conducted by me and my colleagues on molecular mechanisms related to GH, IGF-1 and insulin signaling suggest that Ames dwarfism and GHR knockout prolong life by mechanisms that are overlapping but definitely are not identical to the effects of calorie restriction (CR).
Presently we investigate the role of fat on longevity in Ames dwarf, GHRKO and normal mice. Our newest findings indicated that visceral fat affects insulin signaling differently in long-living Ames dwarf and GHRKO mice in comparison to their normal littermates. This suggests that lack of activation of the GH signaling pathway in visceral fat tissue alters the function of adipocytes in a way that acts positively on whole-body insulin sensitivity. Better understanding of this mechanism could help in developing therapeutic interventions to improve humans health.