Senescent cells, or cells that stop reproducing but do not die, can accumulate in the body over time and fuel chronic inflammation that leads to diseases including cancer and degenerative disorders.
Removal of senescent cells from aging tissues in mice can restore tissue homeostasis and increase healthy longevity. Today, researchers at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), discovered that the immune response to a virus that is widespread in human tissues can identify and eliminate senescent cells in the skin.
For the study, which is published in Cell, researchers analyzed samples of young and old human skin to learn more about the clearance of senescent cells in human tissue.
The researchers found more senescent cells in old skin compared to young skin samples. However, in samples from old individuals, the number of senescent cells did not increase as the individuals progressively aged, suggesting that some type of mechanism is triggered to keep them in check.
The experiments suggested that as a person ages, certain immune cells called killer CD4+ T cells are responsible for preventing the growth of senescent cells. Indeed, higher numbers of killer CD4+ T cells in tissue samples were associated with reduced numbers of senescent cells in aged skin.
When investigating how killer CD4+ T cells keep senescent cells in check, the researchers discovered that senescent skin cells express a protein or antigen produced by human cytomegalovirus, a ubiquitous herpesvirus that establishes a lifelong latent infection in most people without any symptoms. By expressing this protein, senescent cells become targets for attack by killer CD4+ T cells.
“Our study revealed that the immune response to human cytomegalovirus contributes to maintaining the balance of aging organs,” said lead author Shawn Demehri, MD, PhD, director of the high-risk skin cancer clinic at MGH and associate professor of dermatology at Harvard Medical. The 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 regulate the expression of cytomegalovirus antigens.”
These findings, which highlight the beneficial function of viruses living in our bodies, could have a number of clinical applications. “Our research enables a new therapeutic approach to eliminate senescent cells by enhancing the antiviral immune response,” said Demehri. “We are interested in using the immune response to cytomegalovirus as a therapy to eliminate senescent cells in diseases such as cancer, fibrosis and degenerative diseases,” he added.
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