Targeting Pro-Inflammatory Cytokine IL-17 to Slow Skin Aging

Researchers here report that a few cell types in aged skin begin to generate large amounts of IL-17, an inflammatory signal molecule. While the obvious suspect here is cellular senescence, as we know that senescent cells accumulate with age and energetically secrete pro-inflammatory signal molecules, this data suggests that this may not be the case, at least for this particular signal molecule in this particular tissue. The researchers show that blocking IL-17 slows the manifestations of skin aging. The challenge in this sort of approach is that inflammatory signal molecules are needed for the normal immune response to function correctly. The treatment of autoimmune conditions via blockade of various inflammatory signals has meaningful side-effects that include suppression of necessary immune responses. This is less of a concern if treatments target only the skin, but we should hope that researchers can identify more targeted, subtle ways to eliminate only excess inflammatory signaling in the rest of the aging body.

During aging, tissue-specific alterations in the stem cell niche synergize with stem cell-intrinsic changes to contribute to the development of age-associated traits. Aging has been proposed to drive a tissue-dependent proinflammatory microenvironment that perturbs adult stem cell behavior. Infiltration of immune cells into the stem cell niche, or a transcriptional switch of stem cells, contributes to this proinflammatory environment that negatively feeds back to their own fitness. Here we have characterized the effects of the proinflammatory cytokine IL-17 on skin aging.

Our results show that elevated IL-17 signaling, secreted by aged dermal CD4+ T-helper cells, γδ T cells, and innate lymphoid cells, orchestrated many of the age-associated tissue dysfunctions by exertion of pleiotropic effects. IL-17-mediated signaling is heavily linked to the development of chronic inflammatory and autoimmune diseases. In the skin, these diseases include psoriasis, pemphigus, and alopecia areata. Even if none of the clinical signs of these diseases are common with physiological aging, they share an increased aberrant IL-17-based signaling that impedes correct skin function.

Our results strongly suggest that, intriguingly, the local environment of the aged skin resembles a low-level but persistent state of chronic inflammation, with deficient permeability and impaired wound healing that is reminiscent of what occurs in serious skin diseases such as psoriasis. Consequently, anti-IL-17 therapies, already approved for treatment of psoriasis, might be repositioned to other age-associated ailments such as excessive skin dryness or difficulty in repairing damaged skin in the elderly.



There are three IL-17 blocking drugs available: secukinumab, ixekizumab and brodalumab. Probably not worth side effects. Can't find many natural blockers that might lessen IL-17 but the flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit . Could it slow skin aging. Available as a supplement or from eating lots of red berries.

Posted by: august33 at June 17th, 2023 10:37 PM

The black berry with the highest level of cyanidin is probably black crowberry. This grows wild in the arctic/subarctic but is difficult to find commercially.
Close behind are elderberries, aronia berries and blueberries, all much more easily available.They all have that charcteristic tart/sweet taste.
Actual blackberries are pretty good too.
Better than bothering with those ghastly monoclonal antibodies.

Posted by: JLH at June 18th, 2023 4:47 AM
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