Genetic Health Aging Gatekeeper Genes

Are we wired from birth to reach a certain age in life? If we are, is there anything we can do to change that wiring? Genetic researchers believe it is possible to change our bodies on a genetic level so that we may have longer life spans and healthier lives than ever before.

Genetics is the scientific study of the specific traits and characteristics we inherit from birth. Our genes make up the “wiring” that creates the “circuit board” that determines our genetic traits. But what happens when our genes misfire or become damaged? Researchers estimate that hundreds of genes function as repair mechanisms. The two major “repair-mechanism” genes are known as caretaker and gatekeeper genes.

Gatekeeper Genes: What They Are and What They Do

DNA, found within each gene, forms our genetic code that controls the growth, development and function of each cell in our body. Normally, cells grow, divide and eventually die. When something damages the cells’ DNA, caretaker genes repair the damage.

As remarkable as caretaker genes are, they are not always successful. Sometimes DNA is beyond repair. When this happens, gatekeeper genes move in. Gatekeeper genes either inhibit cell division or promote cell death to eliminate damaged cells from the population. This is important because damaged cells will continue to multiply themselves, creating more and more cells that are similarly damaged. One theory is that gatekeeper genes can block the triggers for diseases we are more susceptible to as we age, such as cancer, Alzheimer’s and heart disease.

The Role Gatekeeper Genes Play in Tumor Development and Cancer

The term “gatekeeper gene” was first used in connection with the APC gene, a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of damaged cells, which can develop into cancerous tumors. Today, the term is used for more than the APC gene, and is specific to the tissues in which the gatekeeper gene resides.

Recently, Singapore scientists discovered a gatekeeper gene (RUNX3) that has a role in gastric, breast, lung and bladder cancer. In follow-up research, those same researchers found that the absence or inactivation of RUNX3 may be responsible for the start and growth of colon cancer.

Prior to this discovery, researchers had determined that in most colon cancer cases, the APC gene was disrupted. When this occurs, a protein complex that plays a key role in the development of cancer is activated. This activation has long been thought to be the foundation for the inducement of colon cancer. What this new discovery revealed is that the gatekeeper gene, RUNX3, inhibits the activity of that protein complex.

Gatekeeper Genes and Aging

Researchers have been studying gatekeeper genes that are common to mice and humans. The scientists know that a group of genes known as sirtuins are involved in the aging process. Sirtuins guard against the activation of genes that should not be activated. They do this by protecting the chromatin that directs cell function.

The researchers found that as the mice aged, the chromatin would unwrap and lose its function in directing cells. This made the mice more susceptible to damage to DNA and cancer. The researchers then decided to put more sirtuin back into the mice, which reactivated the protection and extended the lifespan of the subjects.

The hope is to find new approaches to protecting cells against the negative effects of aging by finding drugs that can stabilize genes over time. Gatekeeper genes may hold the key.

Resources

Sierra, Felipe. (n.d.).Is your cellular response to stress killing you? The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61:557-561 (2006). Retrieved from Biomed Gerontology Journals database.

Advantage Business Media. (2008). Gatekeeper gene plays key role in colon cancer. Retrieved June 26, 2009, from the Drug Discovery