title: Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice.
abstract: Hypopituitary Ames dwarf mice were injected either with growth hormone (GH) or thyroxine for a 6-wk period to see whether this intervention would reverse their long life span or the resistance of their cells to lethal stresses. Ames dwarf mice survived 987 ± 24 d (median), longer than nonmutant control mice (664 ± 48), but GH-injected dwarf mice did not differ from controls (707 ± 9). Fibroblast cells from Ames dwarf mice were more resistant to cadmium than cells from nonmutant controls (LD(50) values of 9.98 ± 1.7 and 3.9 ± 0.8, respectively), but GH injections into Ames dwarf mice restored the normal level of cadmium resistance (LD(50)=5.8 ± 0.9). Similar restoration of normal resistance was observed for fibroblasts exposed to paraquat, methyl methanesulfonate, and rotenone (P<0.05 in each case for contrast of GH-treated vs. untreated dwarf mice; P<0.05 for dwarf vs. nonmutant control mice.) T4 injections into Ames dwarf mice, in contrast, did not restore normal life span. We conclude that the remarkable life-span extension of Ames dwarf mice, and the stress resistance of cells from these mice, depends on low levels of GH exposure in juvenile and very young adult mice.
authors: Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
authors: Jacob A
authors: JA
authors: Panici
authors: James M
authors: JM
authors: Harper
authors: Richard A
authors: RA
authors: Miller
authors: Andrzej
authors: A
authors: Bartke
authors: Adam
authors: A
authors: Spong
authors: Michal M
authors: MM
authors: Masternak
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004392:Dwarfism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D013974:Thyroxine / Q000494:pharmacology
chemical_list: D013006:Growth Hormone; D013974:Thyroxine