• Senescent cells are those that have stopped dividing and are unable to perform their
usual functions. As we become older, they build up in many tissues and are suspected
to have a role in age-related illnesses like cancer, arthritis, and cardiovascular disease.
• Senescent cells may contribute to the deterioration in tissue function that comes with
aging, which is another way in which they are considered to be connected to the
ageing process itself.
• Immune cells known as cytotoxic CD4+ T cells have the ability to identify and eliminate
diseased or abnormal cells. Cytotoxic CD4+ T cells destroy their target cells directly, in
contrast to most CD4+ T cells, which often aid in the activation of other immune cells.
• Senescent cells can be destroyed by cytotoxic CD4+ T lymphocytes by focusing
on cytomegalovirus (CMV) antigen. A common virus called CMV has the ability to infect
cells and make them age.
• The study may have discovered that cytotoxic CD4+ T cells may identify and eliminate
these senescent cells by focusing on the CMV antigen, lowering the buildup of
senescent cells, and perhaps postponing or avoiding age-related illnesses.
• Additionally, the researchers discovered that senescent cells produce a CMV antigen,
which suggests that CMV may contribute to the buildup of senescent cells as well as
the ageing process in general.
• According to the research, using cytotoxic CD4+ T lymphocytes to target senescent
cells may be a potential strategy for postponing or avoiding age-related illnesses.
More information:
Methods:
• To investigate how CMV contributes to the buildup of senescent cells, the researchers
employed mice that expressed the CMV antigen (pp89) in their senescent cells.
• They also tested whether cytotoxic CD4+ T cells might eradicate senescent cells in
vitro using human senescent fibroblasts.
Results:
• A subgroup of cytotoxic CD4+ T cells that could recognise and eliminate senescent
cells in vitro was discovered by the researchers.
• In vivo, they discovered that these cytotoxic CD4+ T cells could target senescent cells
with high specificity, preventing their buildup in tissues and enhancing tissue function.
• Senescent cells contain a CMV antigen, which suggests that CMV may contribute to
the buildup of senescent cells. Cytotoxic CD4+ T cells were selectively targeting this
antigen.
• Additionally, the researchers discovered that compared to senescent cells from mice
that did not express the CMV antigen, cells from animals that did express the antigen
had greater amounts of DNA damage and were more resistant to apoptosis
(programmed cell death).
Discussion:
• According to the research, using cytotoxic CD4+ T lymphocytes to target senescent
cells may be a potential strategy for postponing or avoiding age-related illnesses.
• The researchers point out that while CMV could contribute to the buildup of senescent
cells, it is not the sole element at play, and more investigation is required to
comprehend the mechanisms at play.
• The researchers further hypothesise that cytotoxic CD4+ T cells may one day be
employed as a therapeutic for conditions like cancer that are linked to an overgrowth of
senescent cells.
Conclusion:
• The article offers proof that cytotoxic CD4+ T lymphocytes can destroy senescent cells
by specifically attacking a CMV antigen that these cells produce.
• According to the research, CMV could contribute to the accumulation of senescent
cells as well as the ageing process in general.
• The results of the study might inspire novel methods for postponing or avoiding age-
related disorders, but further studies are required to verify their usefulness and safety in
people.
Evidence based articles and links:
• “Cytotoxic CD4+ T cells eliminate senescent cells by targeting cytomegalovirus
antigen”: https://pubmed.ncbi.nlm.nih.gov/37001502/
• “Senescence and Cancer: A Review of Clinical Implications of Senescence and
Senotherapies”: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464619/
• “T-cell immunity against cytomegalovirus in HIV infection and aging: relationships with
inflammation, immune activation, and frailty”: https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC6635075/
• “Impact of CMV upon immune aging: facts and fiction”: https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC6635032/
• “Targeting senescent cells: approaches, opportunities, challenges”: https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC6949083/