New peptide PEPITEM shows promising results in the fight against ‘inflammaging’

A naturally occurring peptide called PEPITEM could potentially rejuvenate the immune response in older people and protect against ‘inflammaging’, which is widely believed to be the root cause of many age-related diseases.

The study, published today in the journal npj Aging, raises the interesting possibility of a protective agent that could dampen age-related inflammation and restore normal immune function in the elderly.

PEPITEM (Peptide Inhibitor of Trans-Endothelial Migration) was first identified at the University of Birmingham in 2015. Although the role of the PEPITEM pathway has already been demonstrated in immune-mediated diseases, these are the first data to show that PEPITEM has the potential to increase health span in an ageing population.

Researchers led by Drs Myriam Chimen, Asif Iqbal and Helen McGettrick investigated how aging negatively impacts the inflammatory response and how PEPITEM can help address this.

In a healthy immune system, PEPITEM regulates the trafficking of immune cells between blood and body tissues, preventing the immune response from becoming exaggerated. In immune-mediated diseases such as rheumatoid arthritis, type 1 diabetes and lupus, the PEPITEM pathway is dysregulated, leading to increased trafficking of immune cells to tissues and resulting in chronic inflammation.

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 affects leukocyte (white blood cell) trafficking in both groups.

Their findings revealed that older mice showed an exaggerated response in terms of the number, subtype and migration of immune cells (including T cells), which could be reduced by administration of PEPITEM. This indicates a decline in the activity of the PEPITEM pathway with age.

The second aspect of the study investigated the possible cause for this decline in PEPITEM activity with age, using B cells derived from younger (less than 45 years) and older (more than 60 years) human donors.

PEPITEM comes from a larger protein secreted by B cells (white blood cells) and its production is activated by a circulating hormone called adiponectin. In the bloodstream, PEPITEM acts on receptors on cells that line the walls of blood vessels.

The researchers found that B cells from older adults were deficient in the signaling pathway that initiates production of the parent protein for PEPITEM (14-3-3ζ).

Dr Chimen said: “We have demonstrated an age-related decline in the PEPITEM-adiponectin pathway and its impact on T cell trafficking, as seen in inflammaging. These really 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.”

University of Birmingham Enterprise has filed several patent families relating to PEPITEM and the components of the PEPITEM molecule responsible for maintaining a normal immune response. The team is seeking collaboration partners, licensees and/or investors. For commercial enquiries, please contact Helen Dunster at University of Birmingham Enterprise.