Nicotinamide Mononucleotide alleviates aging defects of Hutchinson-Gilford progeria syndrome
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder characterized by mutations in the LMNA gene, resulting in progerin accumulation and accelerated aging, with limited therapeutic options currently available. This study demonstrates the significant therapeutic potential of nicotinamide mononucleotide (NMN) in alleviating HGPS phenotypes at both cellular and organismal levels. Using patient-derived induced pluripotent stem cell-mesenchymal stem cells (iPSC-MSCs), we demonstrated that enhancing NAD+ biosynthesis through NMN supplementation effectively restored mitochondrial function, reduced DNA damage and inflammatory markers, and mitigated oxidative stress. Furthermore, in G608G transgenic mouse models receiving NMN administration over four months, we observed significant improvements in fertility and gonadal function, enhanced cardiovascular parameters, ameliorated skin pathology, and extended lifespan. These comprehensive findings establish NMN supplementation as a promising therapeutic strategy for HGPS and potentially other aging-related disorders. Overall design: To compare the different genes expression between G608G MSCs and G608G MSCs treated with NMN.