Aged or senescent cells, which stop dividing but do not die, can accumulate in the body over the years, fueling chronic inflammation that contributes to conditions such as cancer and degenerative disorders.
In mice, removing senescent cells from aged tissues can restore tissue balance and increase life expectancy. Now, a team led by researchers at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), has discovered that the immune response to a virus ubiquitous in human tissues can detect and kill senescent skin cells. .
For the study, which is published in Cell , the scientists analyzed samples of young and old human skin to better understand the removal of senescent cells in human tissues.
The researchers found more senescent cells in the old skin compared to the young skin samples. However, in samples from older people, the number of senescent cells did not increase as they aged, suggesting that there is some kind of mechanism to keep them in check.
The experiments suggested that once a person ages, certain immune cells called killer CD4+ T cells are responsible for preventing senescent cells from increasing. In fact, increased numbers of killer CD4+ T cells in tissue samples were associated with reduced numbers of senescent cells in aged skin.
When they assessed how killer CD4+ T cells kept senescent cells at bay, the researchers discovered that aging skin cells express a protein, or antigen, produced by human cytomegalovirus, a ubiquitous herpesvirus that establishes a lifelong latent infection. in most humans without symptoms. By expressing this protein, senescent cells become targets for killer CD4+ T cell attack.
“Our study has revealed that immune responses to human cytomegalovirus help maintain the balance of aging organs,” says study lead author Shawn Demehri, MD, director of the MGH High-Risk Skin Cancer Clinic and Associate Professor of Dermatology at Harvard Medical School. “Most of us are infected with human cytomegalovirus, and our immune systems have evolved to eliminate cells, including senescent cells, that upregulate the expression of cytomegalovirus antigens.”
These findings, which highlight a beneficial role for viruses living in our bodies, could have various clinical applications. “Our research enables a new therapeutic approach to kill aging cells by enhancing the antiviral immune response,” says Demehri. “We are interested in using the immune response to cytomegalovirus as a therapy to kill senescent cells in diseases such as cancer, fibrosis, and degenerative diseases.”
Demehri notes that the work may also lead to advances in cosmetic dermatology, for example in the development of new treatments to make skin appear younger.