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Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention
Sophie J Hopkin1, Poppy Nathan1, Laleh Pezhman1
1Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Abstract:
Inflammageing leads to uncontrolled leukocyte trafficking in response to inflammatory insults. Here, we used a zymosan-induced peritonitis mouse model on inflammation to investigate the role of the PEPITEM pathway on leukocyte migration in ageing. We then analysed 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. Thus, leading to the exciting possibility that PEPITEM supplementation may represent a potential pre-habilitation geroprotective agent to rejuvenate immune functions.
Insights
Aging impairs the PEPITEM pathway, affecting leukocyte migration during inflammation. Supplementing with PEPITEM rejuvenated immune functions in aged mice and older adults, suggesting a potential geroprotective strategy.
Area of Science:
- Immunology
- Gerontology
- Inflammation Research
Background:
- Inflammageing, or chronic low-grade inflammation associated with aging, disrupts normal immune responses.
- Leukocyte trafficking is crucial for immune surveillance and response but becomes dysregulated with age.
- The PEPITEM pathway's role in age-related leukocyte migration deficits is not well understood.
Purpose of the Study:
- To investigate the role of the PEPITEM pathway in leukocyte migration during aging.
- To determine if PEPITEM pathway functionality is altered in aged mice and older adults.
- To explore the potential of PEPITEM supplementation as a therapeutic strategy to counteract age-related immune dysfunction.
Main Methods:
- Utilized a zymosan-induced peritonitis mouse model to study inflammation and leukocyte migration.
- Assessed PEPITEM pathway functionality in aged mice and older adult human subjects.
- Administered PEPITEM supplementation to evaluate its effect on leukocyte migration and immune function.
Main Results:
- A loss of PEPITEM pathway functionality was observed in aged mice and older adults.
- This pathway dysfunction was linked to uncontrolled leukocyte trafficking during inflammatory insults.
- PEPITEM supplementation successfully rescued the impaired PEPITEM pathway functionality and restored normal leukocyte migration.
Conclusions:
- The PEPITEM pathway plays a critical role in regulating leukocyte migration in response to inflammation, and its function declines with age.
- PEPITEM supplementation demonstrates potential as a geroprotective agent to rejuvenate immune functions in aging individuals.
- Further research into PEPITEM supplementation could lead to novel interventions for age-related immune decline.
