Key Pointers
- Different functions of NAD+ in cellular function and metabolic pathways
- NAD+ is an anti-aging molecule.
- NAD+ is a multifaceted molecule with different roles in different pathologies.
NAD+ is an essential molecule in cellular function and metabolic pathways and is a co-substrate to multiple enzymes. To understand the importance of NAD+, we must identify its crucial role in a variety of functionalities and how its levels affect them. When NAD+ levels decrease with age, functional metabolism decreases as well. This translates into accelerated aging, metabolic disorders, heart dysfunction, and neurodegeneration.
Studies, where boosting NAD+ availability was investigated in rodents, either by diet or by supplementing precursors of NAD+ biosynthesis, have shown promising physiological results. These results included promoted neurosensory function, lipogenesis, increased insulin secretion and sensitivity, decreased insulin resistance, lipogenesis in adipose tissues, kidney protection, and promoted endothelial cell production which prevented cardiovascular diseases.
NAD+ levels have been proven to decrease with aging because of reduced NAMPT expression, excessive PARP activation, DNA damage, and inflammatory changes with age. Targeting NAD+ homeostasis as a means to combat aging has been hypothesized and studied.
Supplementation of NAD+; either as boosting production or reducing breakdown, in rodents has proven to ameliorate and slow down the age-related decline, such as weight gain, insulin resistance, sight and hearing functions, vascular function, and bone density. There’s also evidence of muscle mass and endurance preservation when NAD+ supplementation was administered in rodents.
It is well established that cardiovascular diseases are the most prevalent disorders in the aging population. NAD+ being an essential substrate of Sirtuins, which is a class of enzymes with proven cardiovascular benefits, has been investigated repeatedly.
A recent clinical trial in humans has studied the supplementation of NAD+ in middle-aged and older patients. The results were optimistic physiological outcomes, such as lower systolic blood pressure (SBP) and reduced aortic stiffness, while being well-tolerated with no serious effects. The mean decrease in SBP was 10 mmHg, which has been evidenced to reduce up to 25% the risk of cardiovascular events. This exploratory trial has opened the possibility for future studies to investigate the effects of supplemented NAD+ on a larger scale.
Given its multifaceted abilities, NAD+ also has a role in neurocognitive function. This role can be described as neuroprotective, as it can impede neurodegenerative processes that accelerate with age such as dementia, Alzheimer’s disease, or Parkinson’s. Several studies that investigated models with Parkinson’s disease, found that NAD enhancement was able to improve motor function that was previously compromised by the disease and reduce the risk of developing Parkinson’s altogether.
Other studies in rodents with Alzheimer’s disease have proven that the supplementation of NAD+ had a positive impact on cognitive function and synaptic activity. Other NAD+ enhancing treatments and diets were evidenced to improve age-related neuron degeneration, neuropathy, brain injury, and ischemia, as well as hearing and sight decline.
Conclusion
NAD+ can maintain cellular health and hence has the potential to show anti-aging effects in an increasing world population that is advancing in age. Given its multitude of functions in cellular metabolism, anti-inflammatory pathways, and physiopathology, NAD+ is considered a miracle molecule that can be deployed in fighting aging and different pathologies, due to its multitude of functions throughout the human body.
References
- Sultani G, Samsudeen AF, Osborne B, Turner N. NAD+: A key metabolic regulator with great therapeutic potential. J Neuroendocrinol. 2017;29(10):10.1111/jne.12508. doi:10.1111/jne.12508
- Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547. doi:10.1016/j.cmet.2018.02.011
- Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. Published 2018 Mar 29. doi:10.1038/s41467-018-03421-7