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.
- Schneider A, Zhi X, Bartke A, Kopchick JJ, Masternak MM. Effect of growth hormone receptor gene disruption and PMA treatment on the expression of genes involved in primordial follicle activation in mice ovaries. Age (Dordr). 2014 Aug;36(4):9701. doi: 10.1007/s11357-014-9701-9. Epub 2014 Aug 7. PMID:25099774 [PubMed – in process]
- Stout MB, Tchkonia T, Pirtskhalava T, Palmer AK, List EO, Berryman DE, Lubbers ER, Escande C, Spong A, Masternak MM, Oberg AL, LeBrasseur NK, Miller RA, Kopchick JJ, Bartke A, Kirkland JL. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging (Albany NY). 2014 Jul;6(7):575-86. PMID:25063774 [PubMed – in process]
- Menon V, Zhi X, Hossain T, Bartke A, Spong A, Gesing A, Masternak MM. The contribution of visceral fat to improved insulin signaling in Ames dwarf mice. Aging Cell. 2014 Jun;13(3):497-506. doi: 10.1111/acel.12201. Epub 2014 Feb 12. PMID: 24690289
- List EO, Berryman DE, Funk K, Jara A, Kelder B, Wang F, Stout MB, Zhi X, Sun L, White TA, LeBrasseur NK, Pirtskhalava T, Tchkonia T, Jensen EA, Zhang W, Masternak MM, Kirkland JL, Miller RA, Bartke A, Kopchick JJ. Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles. Endocrinology. 2014 May;155(5):1793-805. doi: 10.1210/en.2013-2086. Epub 2014 Feb 11. PMID: 24517230
- Zhi X, Lamperska K, Golusinski P, Schork NJ, Luczewski L, Golusinski W, Masternak MM. Expression levels of insulin-like growth factors 1 and 2 in head and neck squamous cell carcinoma. Growth Horm IGF Res. 2014 Aug;24(4):137-41. doi: 10.1016/j.ghir.2014.04.003. Epub 2014 Apr 22. PMID:24802266
- Gesing A, Wang F, List EO, Berryman DE, Masternak MM, Lewinski A, Karbownik-Lewinska M, Kopchick JJ, Bartke A. J Gerontol. Expression of Apoptosis-Related Genes in Liver-Specific Growth Hormone Receptor Gene-Disrupted Mice Is Sex Dependent. A Biol Sci Med Sci. 2014 Feb 18. [Epub ahead of print] PMID: 24550353 [PubMed – as supplied by publisher]
- A.Gesing, A.Bartke, F.Wang, M.Karbownik-Lewinska, M.M.Masternak (2011). Key regulators of mitochondrial biogenesis are increased in kidneys of growth hormone receptor knockout (GHRKO) mice. Cell Biochem.Funct.
- J.G.Miquet, J.F.Giani, C.S.Martinez, M.C.Munoz, L.Gonzalez, A.I.Sotelo, R.K.Boparai, M.M.Masternak, A.Bartke, F.P.Dominici, D.Turyn (2011). Prolonged exposure to growth hormone impairs insulin signaling in the heart. J.Mol.Endocrinol.
- M.Kucia, D.M.Shin, R.Liu, J.Ratajczak, E.Bryndza, M.M.Masternak, A.Bartke, M.Z.Ratajczak (2011). Reduced number of VSELs in the bone marrow of growth hormone transgenic mice indicates that chronically elevated Igf1 level accelerates age-dependent exhaustion of pluripotent stem cell pool: a novel view on aging. Leukemia.
- A.Gesing, M.M.Masternak, F.Wang, M.Karbownik-Lewinska, A.Bartke (2011). Deletion of growth hormone receptor gene but not visceral fat removal decreases expression of apoptosis-related genes in the kidney-potential mechanism of lifespan extension. Age (Dordr.).
- A.Gesing, A.Bartke, F.Wang, M.Karbownik-Lewinska, M.M.Masternak (2011). Renal pro-apoptotic proteins are reduced by growth hormone resistance but not by visceral fat removal. Biol.Chem. 392, 475-481.
- A.Gesing, M.M.Masternak, F.Wang, A.Lewinski, M.Karbownik-Lewinska, A.Bartke (2011). Decreased expression level of apoptosis-related genes and/or proteins in skeletal muscles, but not in hearts, of growth hormone receptor knockout mice. Exp.Biol.Med.(Maywood.) 236, 156-168.
- J.Ratajczak, D.M.Shin, W.Wan, R.Liu, M.M.Masternak, K.Piotrowska, B.Wiszniewska, M.Kucia, A.Bartke, M.Z.Ratajczak (2011). Higher number of stem cells in the bone marrow of circulating low Igf-1 level Laron dwarf mice–novel view on Igf-1, stem cells and aging. Leukemia 25, 729-733.
- K.A.Greer, L.M.Hughes, M.M.Masternak (2010). Connecting serum IGF-1, body size, and age in the domestic dog. Age (Dordr.).
- J.A.Panici, J.M.Harper, R.A.Miller, A.Bartke, A.Spong, M.M.Masternak (2010). Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice. FASEB J. 24, 5073-5079.
- A.Louis, A.Bartke, M.M.Masternak (2010). Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice. J.Gerontol. A Biol.Sci.Med.Sci. 65, 344-352.