It is anticipated that the aging population will pose an increasingly serious health and financial challenge globally. Age-related diseases such as cancer, metabolic disorders, and skeletal conditions not only afflict the elderly but also concern younger generations like us, who are the offspring of aging parents. Among these, mobility issues in the elderly are a paramount concern.
Osteoporosis is a chronic condition characterized by decreased bone strength, making individuals more susceptible to fractures and bone microstructure damage. Osteoporosis can be categorized into two main types: primary and secondary. Primary osteoporosis is mainly influenced by factors such as gender and age, while secondary osteoporosis is associated with long-term high-dose glucocorticoid therapy.
NMN Alleviates Skeletal Issues
NMN Stimulates Osteogenic Differentiation and Reduces Bone Loss
In 2019, a research team at Sun Yat-sen University in Guangzhou published a study in “Cell Death & Disease” that demonstrated how Nicotinamide Mononucleotide (NMN) regulates mesenchymal stromal cells in aging bone marrow through the SIRT1 pathway, promoting osteogenesis and reducing fat production.
Mesenchymal stromal cells (MSCs) can differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes. This cell flexibility is essential for the widespread clinical application of mesenchymal stem cells in tissue repair. The research team conducted studies on adult mice, aging mice, and irradiated mice to confirm the impact and potential mechanisms of NMN on MSC proliferation and differentiation in vitro and in vivo.
The results of the research showed that NMN effectively promotes MSC proliferation both in vivo and in vitro in adult, aging, and irradiated mice. This minimizes the issue of heterogeneity during in vitro culture and avoids long-term subculture. Additionally, NMN enhances bone-fat balance in aging and irradiated mice.
The experiments conducted by this research team provide evidence for NMN’s novel role in regulating bone-fat imbalance during the bone aging process through the SIRT1 pathway. It highlights NMN as a valuable therapy to counteract bone loss during the aging process.
NMN Mitigates Glucocorticoid-Induced Osteogenic Inhibition
In 2020, a research team at Nanchang University published a study in “Molecular Medicine Reports” which showed that Nicotinamide Mononucleotide (NMN) mitigates glucocorticoid-induced osteogenic inhibition by regulating the SIRT1/PGC-1α signaling pathway.
Glucocorticoids (Dex) are widely used for treating inflammation and immune rejection reactions. However, their side effects, including glucocorticoid-induced osteogenic inhibition, are considered one of the most severe consequences of this particular type of treatment. Building on previous research, the Nanchang University research team conducted further investigations to explore NMN’s protective effects against another major contributor to osteoporosis.
The study results indicate that glucocorticoids significantly suppress the osteogenic capacity of mouse bone mesenchymal stem cells. NMN, however, mitigates the osteogenic inhibition induced by Dex. Several pieces of evidence also confirm the close association between intracellular NAD+ and bone diseases, with NMN administration significantly increasing intracellular NAD+ levels, showing a favorable response to age-related osteoporosis. NMN also regulates the SIRT1/PGC-1α signaling pathway, affecting SIRT1 protein expression and lowering PGC-1α expression levels.
The experiments conducted by this research team provide evidence for NMN’s potential as a therapeutic target for glucocorticoid-induced osteoporosis through the regulation of the SIRT1/PGC-1α signaling pathway.
References
[1] : 2019 Song, J., Li, J., Yang, F. et al. Nicotinamide mononucleotide promotes osteogenesis and reduces adipogenesis by regulating mesenchymal stromal cells via the SIRT1 pathway in aged bone marrow. Cell Death Dis 10, 336 (2019). https://doi.org/10.1038/s41419-019-1569-2
[2] : 2020 Huang RX, Tao J. Nicotinamide mononucleotide attenuates glucocorticoid‑induced osteogenic inhibition by regulating the SIRT1/PGC‑1α signaling pathway. Mol Med Rep. 2020 Jul;22(1):145-154. doi: 10.3892/mmr.2020.11116. Epub 2020 May 4. PMID: 32377728; PMCID: PMC7248519.
[3]: 2023 Huang Y, Dou Y, Yang B, He B, Zhang X, Zhang K, Yang X. Nicotinamide mononucleotide supplementation mitigates osteopenia induced by modeled microgravity in rats. Cell Stress Chaperones. 2023 Jul;28(4):385-394. doi: 10.1007/s12192-023-01356-7. Epub 2023 May 17. PMID: 37195399; PMCID: PMC10352228.
[4] : 2023 Aobulikasimu, A., Liu, T., Piao, J. et al. SIRT6-PAI-1 axis is a promising therapeutic target in aging-related bone metabolic disruption. Sci Rep 13, 7991 (2023).