Pursuing healthy aging and longevity through natural product and stem cell-driven rejuvenation.

Abstract

Aging is an inevitable biological process associated with progressive physiological decline and increased disease susceptibility. Cellular senescence stands as a key mechanism among the hallmarks of aging, which is characterized by irreversible cell-cycle arrest, chromatin remodeling, and a pro-inflammatory senescence-associated secretory phenotype (SASP). Importantly, SASP drives inflammaging and propagates senescence via a bystander effect, exacerbating tissue dysfunction. Recent advances in senolytic therapies and senostatics offer promising strategies to eliminate or rejuvenate senescent cells, improving physiological function in aged and disease models. Notably, panobinostat has emerged as an effective post-chemotherapy senolytic, mitigating chemoresistance. However, current senolytics face challenges, including off-target effects and limited clinical applicability. Growing evidence highlights natural products (e.g., polyphenols, flavonoids) and stem cell therapies as potential anti-aging interventions, with demonstrated efficacy in age-related disease models and ovarian rejuvenation. Despite progress, key hurdles remain in developing personalized, multi-target therapies that safely modulate aging trajectories. This review explores the mechanisms of cellular senescence, anti-aging mechanisms of phytochemicals, and phytochemicals and stem cell-therapy in ovary rejuvenation. We further discuss the challenges in developing "tailor-made" anti-aging interventions that rewire the aging trajectory, which will be critical for achieving healthy aging.