Xu Yuyan, Wu Mengchen, Fan Yuhang, Zhang Jia, Xue Dixuan, Zhang Ming, Shao Rouyi, Cai Limeng, Liao Xufeng, Zhang Ling, Zhang Jin
Bone Marrow Transplantation Center of the First Affiliated Hospital, and Center for Stem Cell and Regenerative Medicine, Department of Basic Medical Sciences, and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Center for Reproductive Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FASEB J. 2025 Aug 15;39(15):e70875. doi: 10.1096/fj.202500469RR.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by mutations in the LMNA gene, leading to progerin accumulation and accelerated aging. Current therapeutic interventions remain limited. Here, we demonstrate that supplementation with nicotinamide mononucleotide (NMN) markedly ameliorates HGPS-associated phenotypes at both the cellular and organismal levels. In patient-derived induced pluripotent stem cell-mesenchymal stem cells, NMN supplementation enhanced NAD biosynthesis, restored mitochondrial function, reduced DNA damage, and mitigated oxidative stress. Furthermore, 4 months of NMN administration in G608G transgenic mouse models resulted in significant improvements in gonadal function, cardiovascular parameters, skin pathology, and lifespan extension. These comprehensive findings establish NMN supplementation as a promising therapeutic approach for HGPS and potentially other age-related disorders.
哈钦森-吉尔福德早衰综合征（HGPS）是一种由LMNA基因突变引起的罕见遗传疾病，导致早老素积累和加速衰老。目前的治疗干预措施仍然有限。在这里，我们证明补充烟酰胺单核苷酸（NMN）在细胞和机体水平上均能显著改善与HGPS相关的表型。在患者来源的诱导多能干细胞-间充质干细胞中，补充NMN可增强NAD生物合成、恢复线粒体功能、减少DNA损伤并减轻氧化应激。此外，在G608G转基因小鼠模型中给予4个月的NMN可使性腺功能、心血管参数、皮肤病理学和寿命延长得到显著改善。这些全面的研究结果表明，补充NMN是一种有前景的针对HGPS以及潜在其他与年龄相关疾病的治疗方法。
