Two of the features of aging thought to be unavoidable are brittle bones and increased visceral fat, both of which (alone or in combination) are a major contributing factor for the increased mortality seen with aging. As it turns out, both these features are apparently driven by decline in metabolism/OXPHOS, which is driven primarily by a relative NAD+ deficiency (i.e. low NAD+/NADH ratio), and supplementation with NAD+ precursors such as niacinamide may be able to stop/reverse them.
https://www.xiahepublishing.com/2835-6357/FIM-2023-00046
https://www.eurekalert.org/news-releases/1054674
“…Recent studies indicate that oxidative phosphorylation plays a critical role in osteogenesis, the process by which new bone is formed. During osteogenic induction, cells shift their energy metabolism from glycolysis to mitochondrial oxidative phosphorylation, increasing respiratory enzymes, mitochondrial DNA copy number, oxygen consumption, and intracellular ATP content. Bone morphogenetic protein 2 (BMP2) has been shown to trigger metabolic adaptations in mesenchymal stem cells (MSCs), characterized by successive activation of glycolysis and oxidative phosphorylation. NAD+ levels and the NAD+/NADH ratio are crucial for mitochondrial function, linking cellular metabolism to transcriptional events and signaling pathways. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, promotes osteogenesis and reduces adipogenesis in MSCs, protecting bone from aging and damage.”
