Is NAD+ the future of longevity?

Is NAD+ the future of longevity?

Dr. Nandana Bhardwaj

Aging is associated with changes in biological and physiological processes, with some reports suggesting that aging and metabolism are strongly interconnected. Crucial metabolic changes associated with aging include less efficient cellular regeneration, DNA repair defects, and decline in mitochondrial number and functions

Longevity researchers are focusing on NAD+ (nicotinamide adenine dinucleotide), as it fuels various biological processes, and declines gradually with age.

Various nutrients and supplements such as collagen, fisetin, nicotinamide riboside (a precursor of NAD+ and NADH), polyphenols, whey protein, curcumin, and various vitamins are reported to play a significant role in delaying aging, and support longevity. 

NAD+ (nicotinamide adenine dinucleotide) is a cofactor in all living cells, and is needed for biological processes such as DNA repair, metabolic functions, cellular senescence, boosting immune function, gene expression, maintaining circadian rhythm (sleep-wake up cycle), controlling inflammation, and improving longevity. All above-mentioned processes are indispensable for metabolic balance and healthy ageing. 

The first report demonstrating the medical importance of NAD+ was in the treatment of pellagra, with niacin (vitamin B3), a NAD+ precursor. Research has highlighted the role of NAD and its deterioration is linked to various chronic illnesses such as heart disease, diabetes, obesity, vision loss, neurodegenerative diseases and several cancers. In contrast, dietary supplementation that supports  NAD levels, upregulates NAD resulting in beneficial effects against conditions associated with aging.

NAD+ markedly declines with age, with the concentration of NAD+ within the cells of newborns being around three times more compared to young adults, and around eight times that of the elderly, over 71 years of age. As such, maintaining sufficient NAD+ levels may be a solution for age related conditions, and extending lifespan. The main functions of NAD+ include promotion of DNA repair, modulation of immune response and chromosome stability

As cells are unable to absorb NAD directly, dietary supplementation with NAD+ precursors such as nicotinamide riboside (NR), nicotinamide (NAM), nicotinic acid (NA), tryptophan and nicotinamide mononucleotide (NMN) are used to efficiently increase NAD levels. Among these precursors, much focus has been placed on NMN and NR to increase cellular NAD levels

Recent human trials show health benefits of supplementation of NAD+ precursors, such as NMN or NR. The recommended dose of NMN and NR in humans ranges between 1000-2000 mg per day, without any side effects. Though both precursors show beneficial health effects, there are significant differences in them.

  • A study conducted by University of Pennsylvania, USA, oral supplementation of 200 mg/kg NR demonstrated raised NAD+ levels in the liver only but not in other body tissues. In contrast, NMN supplementation reported raised NAD levels in multiple body tissues such as skeletal muscle, blood vessels, kidneys, pancreas, adipose tissues, and even the heart.
  • Previously,  it was unclear whether NMN crosses the blood brain barrier, however, a study whereby NMN was administered via the abdominal cavity showed a rapid increase in  NAD+ levels in the brain, within 15 minutes. This suggests that NMN does cross the blood brain barrier.
  • Various reports show improvement in cognition and memory with NMN administration in mouse and rat models of Alzheimer’s disease
  • Dose-response studies using NMN supplementation indicate the beneficial role of NMN, even at lower doses (100 mg/kg) in terms of neuronal outcomes and physical activity
  • In a recent report, NMN supplementation has demonstrated improvement in vascular aging by stimulating anti-aging micro-RNA gene expression in aged mice with restoration of NAD levels

Currently, there are several major human clinical trials looking at NMN supplementation to increase NAD levels. Institutions running these trials include Washington School of Medicine in St. Louis, USA, Keio University Medical School in Tokyo, Japan and Brigham and Women's hospital in Boston under Harvard longevity scientists. The initial data from phase I and phase II clinical trials results are very encouraging, and support its beneficial health benefits related to aging. 

Maintaining optimal levels NAD+ is essential for maintaining metabolic health in the elderly, and may potentially improve lifespan and healthspan. Dietary measures combined with NMN supplementation, are potential therapeutic strategies to alleviate age-related decline and support longevity.

Dr. Nandana Bhardwaj

Dr.  Bhardwaj is currently working as Senior Research Scientist with STANVAC group. She has received her Ph. D and Post-doctoral research in Biomedical Engineering from Indian Institute of Technology (IIT) Kharagpur, India and School of Materials Science and Engineering, Nanyang Technological University (NTU), Singapore. Her research interests stretching from Biomaterials, Tissue Engineering, Stem cells, drug delivery, wound healing, 3D bioprinting, disease tissue/organ models to regenerative medicine. She has published 35+ articles in top tier journals of biomedical engineering and multiple awards in her name with ~6000 citations and H-index of 19. She has also been featured in “Top 2% Scientist” globally and in biomedical engineering research in a list prepared by Stanford University (published in PLoS Biology, October16, 2020).

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