Sarcopenia is a degenerative skeletal muscle disease closely associated with aging, characterized by the gradual loss of muscle mass and function, significantly affecting the quality of life of elderly individuals. Overall, the severity of sarcopenia varies among patients and muscle groups, increasing the complexity and challenges of treating the condition. Based on the core pathological mechanism of sarcopenia, which involves mitochondrial dysfunction induced by nicotinamide adenine dinucleotide (NAD(+)),This study developed a novel energy-replenishing hydrogel microsphere (NMN@Lipo-s@AHM) for targeted delivery to muscle cells via local injection. Encapsulation in liposomes enhanced the stability of NMN, the SS-31 peptide was used for mitochondrial targeting, and sustained local release was achieved through aldehyde hyaluronic acid methacrylate hydrogel microspheres (AHM). In vitro and in vivo experiments demonstrated that the energy-supplementing hydrogel microspheres significantly alleviated dexamethasone-induced mitochondrial dysfunction and cellular senescence in muscle cells. Transcriptomic and proteomic analyses revealed that the hydrogel microspheres regulate mitochondrial function by activating the "AMPK-SIRT1-PGC1α" signaling pathway, synergistically improving mitochondrial energy metabolism and cellular aging. This study not only provides an efficient strategy for targeted NAD⁺ supplementation but also offers new directions for the mechanistic study and clinical intervention of sarcopenia.

Original link

Energy-replenishing, mitochondria-targeted hydrogel microspheres mitigate sarcopenia via cellular senescence amelioration

Pub Date : 2026-01-07

DOI: 10.1016/j.jconrel.2025.114595

Wei Bao,  Senrui Liu,  Chengcheng Du,  Junyan Liu,  Xuefeng Luo,  Yao he,  Denghua Huang,  Wei Xu,  Yiting Lei,  Wei Huang,  Junyi Liao