Senolytic potential of shea-derived amyrins in senescent fibroblasts
Mikako Hirose1, Shimpei Watanabe2, Yasunori Fujita3
1Department of Cellular Pathology, Research Institute, National Center for Geriatrics and Gerontology, Aichi, Japan.
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.
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