Nicotinamide Riboside (NR) and Nicotinamide MonoNucleotide (NMN) are NAD+ precursors that can be used to increase NAD+ levels in the body and are being used in hundreds of studies for treating a wide range of age related diseases and have shown some benefit on increased lifespan.
Other NAD+ precursors such as Nicotinic Acid (Niacin), or Nicotinamide (NAM) are also quite effective at elevating NAD+ levels (at least in the liver), and are effective at treating some health conditions.
However, numerous studies have also found Niacin and NAM are quite often not as effective for treating health conditions and have not shown the same benefit for increased lifespan.
This study is one such example.
NMN doubled the Sirt1 in stem cells and this increased Sirt1 activity resulted in significantly increased bone growth and decreased fat.
Adding NAM actually prevents the increase in Sirt1 from NMN.
In this study, 300 mg/kg of NMN a day in the drinking water for 3 months resulted in:
- Promotes osteogenesis (bone growth)
- Decreases adipogenesis (growth of fat cells)
- Increased Sirt1 expression required
- Increased MSC (Stem cells)
- Nicotinamide inhibits Sirt1 increase
Nicotinamide mononucleotide (NMN), a key NAD+ intermediate which decreases with age in mammals8, is an efficient therapy against age-associated diseases.
NMN increases osteogenesis and reduces adipogenesis of MSCs via upregulating SIRT1 in aged mice.
NMN Increased Bone Growth
These results indicate that NMN stimulates osteogenesis in aged mice.
Our findings reveal a potential connection between NMN treatment and remedy in osteoporotic and aging mice.
NMN is a valuable therapy for rescuing bone loss during aging.
NMN Decreased Fat Growth
These data suggest that NMN inhibits adipogenesis in aged mice.
NMN Increased Stem cells
NMN promoted MSC self-renewal with strengthened osteogenesis and reduced adipogenesis via upregulating SIRT1 in aged mice.
Our results show that anti-aging agent NMN, can efficiently promote MSCs (stem cells) expansion in vivo.
Our study establishes NMN as a promising potential therapy for MSCs expansion and rejuvenation of aged MSCs.
NMN increases Sirt1
Mechanistically, we found that NMN treatment upregulated SIRT1.
We have further demonstrated that NMN activates Sirtuin1 (SIRT1), which is an NAD+-dependent deacetylase.
Mechanistically, SIRT1 protein upregulation plays an essential role in NMN’s regulation of bone-fat balance.
We demonstrate that SIRT1 protein is essential for NMN to control the osteoblast and adipogenic lineage differentiation.
NAM inhibits Sirt1
It has been known for several years that excess Nicotinamide (NAM) can act to inhibit Sirtuin activity. However it is unclear what impact excess NAM has in vivo, as it is either metabolized to NMN and NAD+ through the salvage pathway, or, methylated to MeNAM and excreted in the urine.
This study doesn’t really answer the question of whether NAM inhibits Sirtuins in vivo. But it is striking how completely the addition of NAM along with NMN shuts down the increased Sirt1 activation.
Previous studies have shown that SIRT1 plays an important role in regulating osteogenesis and adipogenesis in human embryonic stem cells.
These results confirm that the SIRT1 is required for NMN to control osteogenesis and adipogenesis
In summary, we provide evidence for the novel role of NMN in regulating bone-fat imbalance through SIRT1 during skeletal aging.