Articles

Introduction to NAD+: Essential for Cellular Health

Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme found in all living cells, responsible for energy production and numerous cellular processes. NAD+ plays a central role in redox reactions, helping convert nutrients into energy within mitochondria. It also regulates DNA repair, gene expression, and immune responses. As we age, NAD+ levels decline, leading to reduced mitochondrial function and increased susceptibility to age-related diseases.

1. NAD+ and Aging

NAD+ levels naturally decrease with age, contributing to various age-related conditions. Supplementing with NAD+ precursors can help replenish its levels, improving mitochondrial function and overall cellular health. Studies suggest that restoring NAD+ may promote longevity by enhancing the body’s resilience to multiple diseases.

1） Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002. Epub 2014 Apr 29. PMID: 24786309; PMCID: PMC4112140.

https://pubmed.ncbi.nlm.nih.gov/24786309/

2） Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018 Mar 6;27(3):529-547. doi: 10.1016/j.cmet.2018.02.011. PMID: 29514064; PMCID: PMC6342515.

https://pubmed.ncbi.nlm.nih.gov/29514064/

2. NAD+ and Neurodegenerative Diseases 

NAD+ plays a protective role in neurodegenerative diseases such as Alzheimer's and Parkinson’s. Increasing NAD+ levels supports brain health by boosting mitochondrial function, reducing oxidative stress, and potentially slowing neurodegeneration. Preclinical studies have shown positive effects on memory and cognitive function.

3）Lautrup S, Sinclair DA, Mattson MP, Fang EF. NAD+ in Brain Aging and Neurodegenerative Disorders. Cell Metab. 2019 Oct 1;30(4):630-655. doi: 10.1016/j.cmet.2019.09.001. PMID: 31577933; PMCID: PMC6787556.

https://pubmed.ncbi.nlm.nih.gov/31577933/

4）Hou Y, Wei Y, Lautrup S, Yang B, Wang Y, Cordonnier S, Mattson MP, Croteau DL, Bohr VA. NAD+ supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer's disease via cGAS-STING. Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2011226118. doi: 10.1073/pnas.2011226118. PMID: 34497121; PMCID: PMC8449423.

https://pubmed.ncbi.nlm.nih.gov/34497121/

3. NAD+ and Immune Function

NAD+ regulates immune responses and inflammation. Low NAD+ levels are associated with chronic inflammation, which can worsen conditions like diabetes and cardiovascular disease. Enhancing NAD+ supports a healthy immune system, potentially reducing inflammation and improving immune resilience.

5）Myakala K, Wang XX, Shults NV, Krawczyk E, Jones BA, Yang X, Rosenberg AZ, Ginley B, Sarder P, Brodsky L, Jang Y, Na CH, Qi Y, Zhang X, Guha U, Wu C, Bansal S, Ma J, Cheema A, Albanese C, Hirschey MD, Yoshida T, Kopp JB, Panov J, Levi M. NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease. J Biol Chem. 2023 Aug;299(8):104975. doi: 10.1016/j.jbc.2023.104975. Epub 2023 Jul 8. PMID: 37429506; PMCID: PMC10413283.

https://pubmed.ncbi.nlm.nih.gov/37429506/

6）Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141. doi: 10.1038/s41580-020-00313-x. Epub 2020 Dec 22. PMID: 33353981; PMCID: PMC7963035.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963035/

4. NAD+ and DNA Repair

NAD+ is crucial for DNA repair processes. It activates enzymes that repair damaged DNA, and declining NAD+ levels can lead to impaired DNA repair, accelerating aging. Supplementation has shown promise in improving the body’s ability to fix DNA damage, especially in older cells.

7）Navas LE, Carnero A. NAD+ metabolism, stemness, the immune response, and cancer. Signal Transduct Target Ther. 2021 Jan 1;6(1):2. doi: 10.1038/s41392-020-00354-w. PMID: 33384409; PMCID: PMC7775471.

https://pubmed.ncbi.nlm.nih.gov/33384409/

8）Navas LE, Carnero A. NAD+ metabolism, stemness, the immune response, and cancer. Signal Transduct Target Ther. 2021 Jan 1;6(1):2. doi: 10.1038/s41392-020-00354-w. PMID: 33384409; PMCID: PMC7775471.

https://pubmed.ncbi.nlm.nih.gov/33384409/

5.Liver Function Improvement

Recent studies have shown that NAD+ supplementation may have beneficial effects on liver health. By increasing NAD+ levels, NMN helps enhance fat metabolism in the liver disease (NAFLD). This improvement in fat metabolism helps protect the liver from damage, potentially reversing the progression on fatty liver conditions and supporting overall liver function. NAD+ could play a crucial roⅼe in maintaining healthy liver function as we age.

9）Aggarwal S, Trehanpati N, Nagarajan P, Ramakrishna G. The Clock-NAD+ -Sirtuin connection in nonalcoholic fatty liver disease. J Cell Physiol. 2022 Aug;237(8):3164-3180. doi: 10.1002/jcp.30772. Epub 2022 May 26. PMID: 35616339.

https://pubmed.ncbi.nlm.nih.gov/35616339/

10）Zhou CC, Yang X, Hua X, Liu J, Fan MB, Li GQ, Song J, Xu TY, Li ZY, Guan YF, Wang P, Miao CY. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol. 2016 Aug;173(15):2352-68. doi: 10.1111/bph.13513. Epub 2016 Jun 27. PMID: 27174364; PMCID: PMC4945761.

https://pubmed.ncbi.nlm.nih.gov/27174364/