Polyphenol-Rich Extracts from Annurca Apple Differentially Modulate Oxidative Stress-Induced Senescence in Human...

Cellular senescence of dermal fibroblasts is a central mechanism underlying skin aging and is closely linked to oxidative imbalance and mitochondrial dysfunction. In this study, we investigated the senotherapeutic effects of polyphenol-rich extracts obtained from peel and flesh of Malus pumila Mill. cv. Annurca at different ripening stages. Senescence was induced in human dermal fibroblasts by oxidative stress, and the biological activity of unripe and ripe apple extracts was comparatively evaluated. The effects of the treatments were assessed by analyzing cell viability, apoptotic response, oxidative stress levels, mitochondrial functionality, and established molecular and functional markers of cellular senescence. All extracts were well tolerated by young fibroblasts and selectively promoted apoptosis in senescent cells. However, marked differences in biological activity were observed depending on fruit tissue and ripening stage. Unripe peel extract consistently reduced senescence-associated markers, attenuated oxidative stress, and restored mitochondrial homeostasis, indicating a combined senomorphic and senolytic activity. In contrast, ripe peel extract displayed a predominantly senolytic profile associated with increased oxidative stress, while flesh-derived extracts exerted weaker or incomplete effects on senescence pathways. These results demonstrate that Annurca apple polyphenols modulate cellular senescence depending on fruit part and ripening stage. Peel extracts, particularly from unripe fruits, represent potent and sustainable natural senotherapeutics, highlighting the potential of agro-food by-products for anti-aging and skin rejuvenation applications.