Anti-viral immune response may eliminate aging cells - Study

LONDON: Senescent cells, or cells that stop reproducing but do not die, can collect in the body over time and fuel chronic inflammation, which leads to illnesses including cancer and degenerative disorders. Eliminating senescent cells from aged tissues in mice can restore tissue homeostasis and enhance healthy longevity. Today, researchers at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), have discovered that the immune response to a virus that is widespread in human tissues may identify and remove senescent cells in the skin.

For the study, which is published in Cell, the scientists analyzed young and old human skin samples to learn more about the clearance of senescent cells in human tissue. The researchers found more senescent cells in the old skin compared with young skin samples. However, in the samples from old individuals, the number of senescent cells did not increase as individuals got progressively older, suggesting that some type of mechanism kicks in to keep them in check.

Experiments suggested that once a person becomes elderly, certain immune cells called killer CD4+ T cells are responsible for keeping senescent cells from increasing. Indeed, higher numbers of killer CD4+ T cells in tissue samples were associated with reduced numbers of senescent cells in old skin. When they assessed how killer CD4+ T cells keep senescent cells in check, the researchers found that aging skin cells express a protein, or antigen, produced by human cytomegalovirus, a pervasive herpesvirus that establishes lifelong latent infection in most humans without any symptoms. By expressing this protein, senescent cells become targets for attack by killer CD4+ T cells.

"Our study has revealed that immune responses to human cytomegalovirus contribute to maintaining the balance of aging organs," senior author Shawn Demehri, MD, PhD, director of the High-Risk Skin Cancer Clinic at MGH and an associate professor of Dermatology at Harvard Medical School said. He said, "Most of us are infected with human cytomegalovirus, and our immune system has evolved to eliminate cells, including senescent cells, that upregulate the expression of cytomegalovirus antigens."

These findings, which highlight the beneficial function of viruses living in our body, could have a variety of clinical applications. "Our research enables a new therapeutic approach to eliminate aging cells by boosting the anti-viral immune response," Demehri said. "We are interested in utilizing the immune response to cytomegalovirus as a therapy to eliminate senescent cells in diseases like cancer, fibrosis and degenerative diseases," he added.