Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice - PubMed (original) (raw)

Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice

William A Banks et al. Proc Natl Acad Sci U S A. 2010.

Abstract

Both deficiency and excess of growth hormone (GH) are associated with increased mortality and morbidity. GH replacement in otherwise healthy subjects leads to complications, whereas individuals with isolated GH deficiency such as Laron dwarfs show increased life span. Here, we determined the effects of treatment with the GH-releasing hormone (GHRH) receptor antagonist MZ-5-156 on aging in SAMP8 mice, a strain that develops with aging cognitive deficits and has a shortened life expectancy. Starting at age 10 mo, mice received daily s.c. injections of 10 μg/mouse of MZ-5-156. Mice treated for 4 mo with MZ-5-156 showed increased telomerase activity, improvement in some measures of oxidative stress in brain, and improved pole balance, but no change in muscle strength. MZ-5-156 improved cognition after 2 mo and 4 mo, but not after 7 mo of treatment (ages 12, 14 mo, and 17 mo, respectively). Mean life expectancy increased by 8 wk with no increase in maximal life span, and tumor incidence decreased from 10 to 1.7%. These results show that treatment with a GHRH antagonist has positive effects on some aspects of aging, including an increase in telomerase activity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Effects of MZ-5-156 on life expectancy. (A) Effects on fraction survival for all mice. (B) Surviving mice before change in proportional hazards at about day 55.

Fig. 2.

Effects of MZ-5-156 on cognition. (A) Improvement in acquisition (learning) but not retention (memory) at age 12 mo after 2 mo of treatment. (B) Improvement in learning as measured by lever press in 12-mo-old mice after 2 mo of treatment. (C) Improvement in memory in the step-down passive avoidance in 14-mo-old mice after 4 mo of treatment. (D) Improvement in memory as measured by object recognition in 14-mo-old mice (4 mo of treatment) but not at 17 mo (7 mo of treatment).

Fig. 3.

Effects of MZ-5-156 on measures of brain oxidative stress. Increased GSH (A) and decreased GPx (B) indicate decreased oxidative stress. MDA (C) and GR (D) were unchanged.

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Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice - PubMed (original) (raw)