The novel nano-selenium supplement extends lifespan and delays multi-organs aging by regulating the Sik1 pathway through maintaining calcium homeostasis

While selenium regulates redox homeostasis and aging, its therapeutic use is limited by bioavailability and toxicity. We developed diselenide-bridged mesoporous silica nanoparticles (SeMSNs) as a novel delivery system.

SeMSNs delayed cellular senescence in fibroblasts and H₂O₂-induced models by reducing oxidative stress and senescence markers (p16, p21). In aged mice, SeMSNs extended lifespan, reduced frailty, and improved multiple age-related conditions including muscle atrophy, renal dysfunction, cognitive decline, and hepatic steatosis while restoring metabolic balance. Mechanistically, SeMSNs upregulated selenoproteins (GPx1, SelK), restored calcium homeostasis, attenuated ER stress, and inhibited NFATc2-mediated Sik1 transcription.