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Researchers at Cedars-Sinai have discovered that growth hormone in the colon increases as the colon ages-a discovery that helps guide the development of new anti-aging therapies.
The results of the study, published in the peer-reviewed journal Cell Reports, provide important clues about how local non-pituitary growth hormone (npGH) is activated in aging colon tissue, thereby starting the first step in tumor development.
We are trying to determine the mechanism of aging and what measures can be taken to prevent or improve aging-related diseases. We showed for the first time how npGH affects the aging process and how its signals can be used as a potential therapy to improve cancer and other age-related diseases. ”
Shlomo Melmed, MB, ChB, co-author, Executive Vice President of Academic Affairs and Dean of Cedars-Sinai School of Medicine
Aging is a complicated process. One of the signs is excessive damage to DNA. Many biological and environmental factors (such as ultraviolet light, smog, and chemotherapy) can damage an individual’s DNA. Although the body has a mechanism to repair part of the damage, continuous damage can interfere with the process of DNA self-repair.
Damaged DNA usually activates a core protein called ATM, which is responsible for repairing the strands that create the molecular structure of DNA. This process relies on several additional proteins, including a protein called p53, a tumor suppressor that plays an important role in DNA self-repair.
Although the protein p53 acts as a protective mechanism for DNA, it can also trigger the activation of growth hormone.
Researchers at Cedars-Sinai set out to study the relationship between proteins and hormones. “The results of the study are amazing,” said Dr. Vera Chesnokova, an associate professor of medicine and the study’s first author. “We have seen that DNA damage triggers growth hormone in colon cells, which in turn causes more DNA damage, leading to huge changes in the microenvironment of the epithelial tissue.”
These changes in the microenvironment provide a favorable environment for the rapid growth, division and transformation of cells-this is the initial step of tumor development.
To study DNA repair in the colon, the researchers used human intestinal organoids, which are tiny three-dimensional cultures derived from stem cells similar to human colon tissue. These organoids were developed by Dr. Robert Barrett, an assistant professor of medicine at Cedars-Sinai and a co-author of the study.
When studying these organoids, the researchers found that the growth hormone npGH prevented p53 from exerting its effects, leading to further DNA damage.
The team was surprised by this discovery. Unlike circulating pituitary growth hormone, which decreases with age, colon tissue growth hormone npGH increases with age.
The study suggests that using available drugs designed to block growth hormone receptors to disrupt npGH signaling may be used as an anti-aging treatment. It can also potentially help cancer patients undergoing DNA damage treatments such as chemotherapy and radiation therapy.
Chesnokova said: “The results of this study provide an innovative method that may extend human lifespan and open up new ways to understand the accumulation mechanism of age-related DNA damage.”
Labels: aging, cancer, cells, chemotherapy, DNA, DNA damage, drugs, endocrine, growth hormone, hormones, laboratory, medicine, molecules, organoids, proteins, radiotherapy, receptors, research, stem cells, tumors
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Post time: Dec-22-2021