Nicotinamide Mononucleotide Alleviates Aging Defects in Hutchinson-Gilford Progeria Syndrome.

Abstract

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 NADbiosynthesis, 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.