Cellular senescence is a biological process involved in aging and neurodegenerative disease progression, characterized by cell-cycle arrest, oxidative stress, persistent DNA damage, and development of a pro-inflammatory senescence-associated secretory phenotype (SASP). While replicative senescence results from exhaustion of cellular proliferative capacity, stress-induced premature senescence (SIPS) can be induced by multiple triggers, contributing to various pathological conditions. Among compounds reported to modulate cellular senescence, quercetin (QUE), a dietary flavonoid with antioxidant and anti-inflammatory properties, has emerged as a promising modulator of senescence-related pathways. This study investigated the protective effects of QUE against oxidative stress-induced senescence in SH-SY5Y neuronal-like cells. Cells were exposed to H2O2 (25 μM) to trigger early SIPS and subsequently treated with QUE (2.5 and 5 μM) for 24 h. H2O2 induced a senescence-like phenotype characterized by increased senescence-associated β-galactosidase (SA-β-gal) activity, lamin-B1 depletion, activation of p53/p21 pathway, modulation of Bcl-2/Bax ratio, and upregulation of SASP mediators, including NF-κB, MCP-1 and PAI-1. QUE treatment significantly attenuated these markers in a dose-dependent manner. These effects were associated with the enhancement of Nrf2-linked antioxidant responses, indicating a potential contribution to QUE senescence-modulating properties. These findings support the potential of QUE as a senescence-modulating compound against oxidative stress-induced neuronal senescence through the modulation of key molecular pathways, along with the enhancement of Nrf2-associated antioxidant defenses.
Salamone et al. (Fri,) studied this question.