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

Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22272-7. doi: 10.1073/pnas.1016369107. Epub 2010 Dec 6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cognition / drug effects
  • Cognition Disorders / genetics
  • Cognition Disorders / metabolism
  • Growth Hormone-Releasing Hormone / antagonists & inhibitors*
  • Growth Hormone-Releasing Hormone / genetics
  • Growth Hormone-Releasing Hormone / metabolism
  • Laron Syndrome / genetics
  • Laron Syndrome / metabolism
  • Longevity / drug effects*
  • Mice
  • Oxidative Stress / drug effects*
  • Sermorelin / analogs & derivatives*
  • Sermorelin / pharmacology
  • Telomerase / genetics
  • Telomerase / metabolism*

Substances

  • MZ 5-156
  • Sermorelin
  • Growth Hormone-Releasing Hormone
  • Telomerase