Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice.
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.
Panici
Jacob A
JA
Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Harper
James M
JM
Miller
Richard A
RA
Bartke
Andrzej
A
Spong
Adam
A
Masternak
Michal M
MM
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
D013006:Growth Hormone; D013974:Thyroxine