title: Decreased levels of proapoptotic factors and increased key regulators of mitochondrial biogenesis constitute new potential beneficial features of long-lived growth hormone receptor gene-disrupted mice.
abstract: Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results suggest new features of GHRKO mice that may positively affect longevity-decreased levels of proapoptotic factors and increased levels of key regulators of mitochondrial biogenesis. The alterations in levels of the proapoptotic factors and key regulators of mitochondrial biogenesis were not further improved by two other potential life-extending interventions-calorie restriction and visceral fat removal. This may attribute the primary role to GH resistance in the regulation of apoptosis and mitochondrial biogenesis in GHRKO mice in terms of increased life span.
authors.affiliation: Department of Oncological Endocrinology, Medical University of Lodz, Lodz, Poland. adges7@wp.pl
authors.forename: Adam
authors.initials: A
authors.lastname: Gesing
authors.forename: Michal M
authors.initials: MM
authors.lastname: Masternak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lewinski
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Karbownik-Lewinska
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D063269:Mitochondrial Turnover / Q000235:genetics*; D023421:Models, Animal; D011986:Receptors, Somatotropin / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D011986:Receptors, Somatotropin