| First Author | Khan NA | Year | 2026 |
| Journal | Cell Rep | Volume | 45 |
| Issue | 9 | Pages | 117849 |
| PubMed ID | 42669151 | Mgi Jnum | J:393367 |
| Mgi Id | MGI:8406862 | Doi | 10.1016/j.celrep.2026.117849 |
| Citation | Khan NA, et al. (2026) NAD(+) precursor treatment prevents cardiomyopathy but disrupts erythroid maturation in mitochondrial progeria. Cell Rep 45(9):117849 |
| abstractText | Nicotinamide adenine dinucleotide (NAD(+)) plays a central role in energy metabolism, and its decline is linked to various degenerative diseases. While NAD(+) restoration holds therapeutic promise, its long term, tissue-specific consequences remain poorly understood. We investigated effects of nicotinamide riboside (NR) supplementation for "mutator" mice manifesting mitochondrial progeria. Our results reveal strikingly divergent outcomes: in proliferative bone marrow, NR-treated mutators show reductive stress with accumulation of NADH/NADPH, altered amino acid, nucleotide, folate levels, and impaired heme biosynthesis. In blood, erythrocyte maturation defects are aggravated, exacerbating anemia. Conversely, in postmitotic cardiac tissue, NR enhanced contractility, reduces stress response markers and normalized metabolic profile. These findings indicate that while beneficial for heart, chronic NAD(+) boosting can compromise erythrocyte maturation in the context of mitochondrial disease. The data emphasize importance of evaluating systemic effects of NAD(+) boosting therapies beyond the primary affected tissues and development of tissue-specific metabolic interventions for degenerative diseases. |
