Senolytic Potential of Shea-Derived Amyrins in Senescent Fibroblasts.

Abstract

Senescent cells contribute to tissue dysfunction and the progression of age-related diseases. Senolytic therapies, which selectively eliminate these cells, have demonstrated beneficial effects in preclinical models by restoring tissue function and delaying age-related decline. Naturally occurring compounds are gaining attention due to their structural diversity and low toxicity. Among these, triterpenes, plant-derived molecules with anti-inflammatory and protective properties, are emerging as therapeutic candidates for targeting cellular senescence. Here, we aimed to evaluate the senolytic activity of β-amyrin, a plant-derived triterpene, in established fibroblast models. Using senescent cells of murine and human origin, we found that β-amyrin selectively induced cell death in senescent cells. Mechanistic analyses suggest that this effect involves cannabinoid receptor 2 signaling and proceeds independently of caspase activation. These findings highlight β-amyrin as a promising senolytic compound with a potentially unique mechanism of action.