A naturally occurring peptide called PEPITEM could rejuvenate the immune response in older individuals and protect against ‘inflammageing’, which is widely believed to be the root cause of many age-related diseases. Inflammageing, a term combining “inflammation” and “ageing,” refers to the chronic, low-grade inflammation that naturally increases as people age (1^✔ ✔Trusted Source
Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention

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What is PEPITEM

PEPITEM (Peptide Inhibitor of Trans-Endothelial Migration) is a naturally occurring peptide initially identified at the University of Birmingham in 2015. While its role has already been demonstrated in immune-mediated diseases, recent studies suggest PEPITEM could increase healthspan in aging populations by mitigating age-related inflammation and restoring normal immune function.

A study published in the journal npj Aging explores the potential of PEPITEM as a protective agent against inflammageing. Researchers led by Drs. Myriam Chimen, Asif Iqbal, and Helen McGettrick investigated how aging influences the inflammatory response and how it can be rescued by PEPITEM.

The Role of PEPITEM in a Healthy Immune System

In a healthy immune system, PEPITEM regulates the trafficking of immune cells between the blood and body tissues, ensuring the immune response is not exaggerated. In immune-mediated diseases such as rheumatoid arthritis, type 1 diabetes, and lupus, the PEPITEM pathway is dysregulated, leading to chronic inflammation.

The researchers used an animal model to study the effect of an immune challenge in young and older mice. They examined the extent to which PEPITEM influences leukocyte (white blood cell) trafficking in both groups. Findings revealed that older mice exhibited an exaggerated immune response, which could be reduced by administering PEPITEM. This suggests a decline in PEPITEM pathway activity with age.

Investigating the Cause of Decline in PEPITEM Activity

The second part of the study examined the potential cause of this decline in PEPITEM activity using B-cells harvested from younger (under 45 years) and older (over 60 years) human donors. PEPITEM originates from a larger protein secreted by B-cells, triggered by a circulating hormone called adiponectin. In the bloodstream, PEPITEM acts on receptors on cells lining blood vessel walls.

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). This age-related decline in the PEPITEM-adiponectin pathway influences T-cell trafficking, contributing to inflammageing.

Potential Implications of PEPITEM

Dr. Chimen stated, “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 inflammageing. 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.”

The findings indicate that PEPITEM could serve as a novel therapeutic agent to combat age-related diseases by restoring immune balance and reducing chronic inflammation. Further research and clinical trials will be necessary to develop effective PEPITEM-based therapies for human use, but the potential benefits are promising.

In summary, PEPITEM represents a significant advancement in understanding and potentially managing age-related immune decline and inflammageing. With further research, it could become a cornerstone in geriatric medicine, offering older adults improved healthspan and protection against a variety of age-related diseases.

Reference:

1. Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention – (https://rdcu.be/dOiTl )

Source-Medindia