The reagent nicotinamide mononucleotide (NMN) docks onto the nucleosome assembly protein 1 like-2 (NAP1L2) to reinvigorate the “stemness” of bone mesenchymal stem cells.
The breakdown and generation of new bone cells (osteogenesis) declines as people age. The disarray of bone regeneration stems from depleted stem cells in their original, youthful state (stemness). The bone stem cells’ stemness declines due to the accumulation of mutations in the stem cells as they progress through the cell cycle to maturity as osteoblasts.
In other words, as stem cells become osteoblasts, bones harden, may fracture easily, and develop pores (osteoporosis), leading to frailty. Clinicians can measure frailty using the Frailty Index, a number that is a proxy to the state of an elderly individual’s overall fitness and health. For these reasons, research has been geared toward finding ways to maintain stemness of bone mesenchymal stem cells (BMSCs), the stem cells that produce osteoblasts and, concomitantly, bone tissue.
NMN Genetically Refurbishes Elderly Human Bone Stem Cells
Previous research has shown that the immediate precursor to nicotinamide adenine dinucleotide (NAD+), nicotinamide mononucleotide (NMN), restores bone tissue health in rodents like mice and rats. With that being said, Liu and colleagues from Tianjin Medical University utilized BMSCs from young and old patients to test whether administering NMN restores the epigenetic code, the youthful pattern of gene expression, in these cells. In doing so, the Tianjin-based research team found that the BMSCs undergoing chemotherapeutic treatment and oxidative stress showed enhanced stemness after being treated with NMN. Interestingly enough, the China-based team reported further data showing that NMN binds to DNA to potentially rejuvenate gene expression profiles.
Increased expression of the protein nucleosome assembly protein 1-like 2 (NAP1L2) correlates with aging. Liu and colleagues hypothesized that with increased NAP1L2 levels, this protein, a nucleosome chaperone, removes molecular tags called acetyl groups from proteins that DNA wraps around (nucleosomes). NAP1L2 also recruits the deacetylase protein Sirtuin1 (SIRT1) that removes acetyl groups from promoter regions of genes that drive osteogenesis.