IL-15 as an Exercise Mimetic that Improves Wound Healing in Old Mice

Researchers here demonstrate that providing the cytokine IL-15 to older mice improves wound healing. The surrounding context suggests that this is a part of the stress response systems that link exercise to health benefits, acting through at least mitochondrial function, and no doubt other pathways as well. Since the mitochondria in cells throughout the body undergo a series of detrimental changes with age, faltering in their ability to deliver energy store molecules to power cellular processes, most methods of intervening in this decline might be expected to produce some degree of benefit. This is the case even when, as here, the intervention is essentially compensatory, addressing only a proximate cause rather than the underlying accumulation of damage that drives the manifestations of aging.

Impaired wound healing in elderly individuals increases infection risk and prolongs surgical recovery, but current treatment options are limited. Low doses of interleukin 15 (IL-15) that mimic exercise responses in the circulation improve skin structure and increase mitochondria in uninjured aged skin, suggesting that IL-15 is an essential mitochondrial signal for healing that is lost during aging.

Here we used gene microarray analysis of old and young murine epidermal stem cells and demonstrate that aging results in a gene signature characteristic of bioenergetic dysfunction. Intravenous IL-15 treatment rescued chronological aging-induced healing defects and restored youthful wound closure in old, sedentary mice. Additionally, exercise-mediated improvements in the healing of aged skin depend upon circulating IL-15. We show that IL-15 induces signal transducer and activator of transcription 3 (STAT3) signaling characteristic of young animals, reduces markers of growth arrest, and increases keratinocyte and fibroblast growth. Moreover, exercise or exercise-mimicking IL-15 treatment rescued the age-associated decrease in epidermal mitochondrial complex IV activity.

Overall, these results indicate that IL-15 or its analogs represent promising therapies for treating impaired wound healing in elderly patients.

Link: https://doi.org/10.1074/jbc.RA119.010740

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