Researchers from the University of Birmingham have discovered that a naturally occurring peptide called PEPITEM could potentially rejuvenate the immune response in older individuals and protect against “inflammaging,” which is widely believed to be the root cause of many age-related diseases.
The findings are published in npj Aging in an article titled, “Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention.”
PEPITEM (Peptide Inhibitor of Trans-Endothelial Migration) was initially identified at the University of Birmingham in 2015. While the role of the PEPITEM pathway has already been demonstrated in immune-mediated diseases, this is the first data showing that PEPITEM has the potential to increase healthspan in an aging population.
“Inflammaging leads to uncontrolled leukocyte trafficking in response to inflammatory insults,” the researchers wrote. “Here, we used a zymosan-induced peritonitis mouse model on inflammation to investigate the role of the PEPITEM pathway on leukocyte migration in aging. We then analyzed whether PEPITEM could modulate leukocyte migration in older adults. We observed a loss of functionality in the PEPITEM pathway, which normally controls leukocyte trafficking in response to inflammation, in older adults and aged mice and show that this can be rescued by supplementation with PEPITEM.”
The study raises the possibility of a protective agent that could dampen age-related inflammation and restore normal immune function in older adults.
The researchers used an animal model to study the effect of an immune challenge in young and older mice and the extent to which PEPITEM influences leukocyte (white blood cell) trafficking in both groups.
Their findings revealed that older mice exhibited an exaggerated response in terms of the number, subtype, and migration of immune cells (including T cells), which could be reduced by administering PEPITEM.
The second aspect of the study examined the potential cause for this decline in PEPITEM activity with age by using B cells harvested from younger (under 45 years) and older (over 60 years) human donors.
The researchers found that B cells from older adults had a deficit in the signaling pathway that triggers the production of the parent protein for PEPITEM (14-3-3ζ).
One of the article’s authors, Myriam Chimen, PhD, said, “We have shown an age-related decline in the PEPITEM-adiponectin pathway and demonstrated the influence this has on T-cell trafficking, as seen in inflammaging. These truly exciting results raise the possibility of developing a geroprotective agent that not only reduces excessive inflammation in old age but also supports good immune function in older people.”
