Growth Hormone-releasing Hormone Antagonist Exhibits Benefits on Some Aspects of Aging

A University of Miami Miller School of Medicine researcher and collaborators at other institutions have developed an antagonist to growth hormone that seems to reverse some of the signs of aging. The just published finding appears to overturn recent thinking that growth hormones could prolong youth.

It’s a well-known fact that the aging process brings on a decrease in mental capacity and physical functioning. The human body, as it ages, also displays an increased tendency toward tumor development, both benign and malignant. Researchers have proposed that a number of factors play a role in the physical and mental breakdown, including oxidative stress, variation in hormonal levels and telomerase activity – an enzyme at the end of chromosomes which protects DNA. The search lies in determining what will slow down, if not reverse, this aging process.

Growth hormone (GH) is one of the hormones associated with aging, since it dramatically decreases as people get older. This led scientists to propose replacing growth hormone in the hopes of slowing the aging process, but several clinical trials have proven the opposite — that replacing GH is associated with adverse conditions such as additional heart disease and increased cancer incidence, along with overall accelerated aging. In essence, too much or too little growth hormone leads to increased mortality.

A group of scientists, including Andrew V. Schally, Ph.D., M.D.h.c., D.Sc.h.c., the 1977 Nobel Prize winner for Physiology or Medicine, Distinguished Medical Research Scientist of the Miami Department of Veterans Affairs, Distinguished Professor in the Department of Pathology at the Miller School of Medicine and professor in the Division of Hematology-Oncology, have taken another approach. Led by William A. Banks, M.D., Geriatrics Research Education and Clinical Center at the Veterans Affairs Puget Sound Health Care System and Professor of Internal Medicine and Geriatrics at the University of Washington School of Medicine in Seattle, and co-author John E. Morley, M.D., Professor of Internal Medicine at St. Louis University School of Medicine, these scientists examined the effects of inhibiting the secretion of growth hormone.

Knowing that excess levels of GH can accelerate aging, Banks, Schally and Morley led a team in testing an antagonist of GH-releasing hormone (MZ-5-156) made in Schally’s laboratory. They examined its effects on life span and found that it had a positive impact. Their findings are published in the December 6 online edition of the Proceedings of the National Academy of Sciences.
Morley points out that many older people have been taking growth hormone to rejuvenate themselves. He says “these results strongly suggest that growth hormone when given to middle aged and older persons may be hazardous.”

Schally, Banks and their colleagues used the SAMP8 mouse model, a strain with a natural mutation that makes it a natural model in Alzheimer’s work. This team examined the effects of the GHRH antagonist MZ-5-156 on various aspects of aging and found that there was a beneficial effect on most of the critical markers: oxidative stress, telomerase activity, median life expectancy, tumor incidence and memory.

“These results tell us that not only can GHRH antagonists have a positive effect on aging,” says Schally, “but we also discerned some of the mechanisms involved.”

In other studies, antagonist MZ-5-156, like many GHRH antagonists, was able to inhibit several human cancers, including prostate, breast, brain and lung cancers. In the present study, it similarly decreased the number of tumors in animals. It also had positive effects on learning, and showed a short-term improvement in memory. The antioxidant actions led to less oxidative stress which decreased amyloid proteins, a hallmark of Alzheimer’s disease, thus reversing cognitive impairment in the aging mouse.

Overall, the researchers found that MZ-5-156 had positive effects on oxidative stress in the brain, improving cognition, telomerase activity and life span, while decreasing tumor activity. Banks says that the study “determined that antagonists of growth hormone-releasing hormone have beneficial effects on aging.”

Future studies are expected to confirm and expand these findings using the new GHRH antagonists made in Schally’s laboratory in the VA and the Miller School.

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