The study shows that a skin‑secreted peptide called CLSP can lower a common aging marker in skin cells that have been damaged by peroxide or UV light, suggesting it might help keep skin cells from becoming senescent.

Calmodulin-like skin protein (CLSP) is a secreted peptide that is produced by skin keratinocytes and some related epithelial cells. It has previously been shown that CLSP is recruited via the bloodstream into the central nervous system where it likely exerts a neuroprotective effect against toxicity related to Alzheimer's disease (AD) by binding to the heterotrimeric humanin receptor and activating intracellular survival signaling. However, it remains to be elucidated whether secreted CLSP shows a protective effect in the skin tissues. In the current study, using primary keratinocytes treated with hydrogen peroxide (H₂ O₂ ) or exposed to ultraviolet (UV) irradiation as senescence models of keratinocytes, we addressed whether CLSP affects senescence in skin keratinocytes. We found that CLSP expression was upregulated by H₂ O₂ or UV in keratinocytes. Furthermore, co-incubation with recombinant CLSP reduced the increase in senescence-associated β-galactosidase-positivity in keratinocytes that were induced by H₂ O₂ or UV. These results suggest that CLSP may function as a senescence-suppressing factor in keratinocytes.