Greek endemic oregano species Origanum calcaratum, analyzed via LC-MS across methanolic and hydromethanolic extracts, yielded 27 constituents dominated by phenolic compounds. Both extracts and isolated rosmarinic acid demonstrated noncytotoxicity in healthy cells while exhibiting concentration-dependent senolytic activity in Li-Fraumeni syndrome fibroblasts — a p53-mutant cell line prone to accelerated senescence. The hydromethanolic extract and rosmarinic acid showed significant senolytic effects at low concentrations; the methanolic extract required higher doses for comparable activity.
Senolytics — compounds that selectively eliminate dysfunctional senescent cells — represent one of geroscience's most active therapeutic frontiers. The selective toxicity profile here is the critical signal: killing senescent cells without harming healthy tissue is precisely the challenge that has limited clinical translation of earlier senolytic candidates like navitoclax. Rosmarinic acid is already well-characterized as an antioxidant and anti-inflammatory polyphenol found in rosemary, sage, and various Lamiaceae species, but its senolytic mechanism remains underexplored. The use of Li-Fraumeni cells is methodologically reasonable for senescence modeling but limits generalizability — these are genetically aberrant human cells, not primary aged tissue. This is early-stage in vitro work: no animal data, no mechanistic pathway confirmed, no dosing equivalence to human intake established. That said, the selectivity finding and low-concentration efficacy of the hydromethanolic extract make this incrementally valuable, warranting follow-up studies identifying the precise bioactive fractions and upstream senescence pathways involved.
