Aging, or senescent cells, which stop dividing but don’t die, can accumulate in the body over the years and fuel chronic inflammation that contributes to conditions such as cancer and degenerative disorders.
In mice, eliminating senescent cells from aging tissues can restore tissue balance and lead to an increased healthy lifespan.
A team led by investigators at Massachusetts General Hospital (MGH), has found that the immune response to a virus that is ubiquitously present in human tissues can detect and eliminate senescent cells in the skin.
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.
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. 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,” says senior author Shawn Demehri, MD, PhD.
“Our research enables a new therapeutic approach to eliminate aging cells by boosting the anti-viral immune response,” says Demehri. “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.”
Tatsuya Hasegawa, Tomonori Oka, Heehwa G. Son, Valeria S. Oliver-García, Marjan Azin, Thomas M. Eisenhaure, David J. Lieb, Nir Hacohen, Shadmehr Demehri. Cytotoxic CD4+ T cells eliminate senescent cells by targeting cytomegalovirus antigen. Cell, 2023; 186 (7): 1417 DOI: 10.1016/j.cell.2023.02.033
Massachusetts General Hospital. “Boosting the body’s anti-viral immune response may eliminate aging cells: Strategy could restore tissue balance and target cells that contribute to aging-related diseases.” ScienceDaily. ScienceDaily, 30 March 2023. <www.sciencedaily.com/releases/2023/03/230330172112.htm>.
Photo by Rod Long