Boosting NAD+ Levels for Healthy Aging 

In the quest for eternal youth, scientists have long sought after the elusive key to slowing down the aging process. While the fountain of youth may remain a mythical concept, recent research has uncovered a promising candidate: nicotinamide adenine dinucleotide, or NAD+. This molecule, found in every cell of our bodies, plays a crucial role in various cellular processes, including energy production, DNA repair, and gene expression [1]. However, as we age, NAD+ levels decline, which may contribute to various age-related diseases and conditions [2].

NAD+ is a coenzyme found in all living cells, playing a crucial role in transferring electrons during metabolic reactions. It exists in two forms: NAD+ and its reduced form, NADH. NAD+ is essential for the function of enzymes like sirtuins and PARPs, which regulate key cellular processes, including DNA repair, inflammation, and mitochondrial function. As we age, NAD+ levels decline due to various factors, including decreased biosynthesis, increased consumption by enzymes, and impaired recycling pathways. This decline in NAD+ has been implicated in age-related diseases such as neurodegenerative disorders, metabolic dysfunction, and cardiovascular diseases [1]. Therefore, strategies to boost NAD+ levels have garnered significant interest in the field of aging research.

To address this decline, researchers have investigated various strategies to boost NAD+ levels. One promising approach is through Nicotinamide Riboside (NR). NR is a precursor to NAD+ and has been shown to effectively raise NAD+ levels in various preclinical and clinical studies [3]. NR supplementation can enhance NAD+ biosynthesis pathways, thereby replenishing cellular NAD+ levels [4].

Additionally, both fasting and caloric restriction have been shown to increase NAD+ levels. These dietary interventions activate pathways like AMPK and SIRT1, which stimulate NAD+ biosynthesis and promote cellular health [5].

Moreover, regular physical activity has been linked to increased NAD+ levels [6]. Exercise activates the NAD+- dependent enzyme, sirtuin 1 (SIRT1), which plays a role in mitochondrial biogenesis, energy metabolism, and stress resistance [7,8].

Furthermore, certain foods contain precursors or compounds that can support NAD+ production. For example, foods rich in niacin (vitamin B3), such as yeast, meat, fish, and nuts, provide substrates for NAD+ synthesis [9].

While natural strategies such as supplementation with NAD+ precursors, fasting, exercise, and dietary modifications offer promising approaches to boost NAD+ levels, further research is needed to elucidate their long-term effects and optimal dosages. Understanding the intricacies of NAD+ metabolism and its role in aging and disease is essential for developing effective interventions to promote healthy aging and longevity.

Author: Frida Matiyevskaya

The Fountain of Youth by Lucas Cranach the Elder (1546).


References:

  1. Covarrubias, A.J., Perrone, R., Grozio, A. et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol 22, 119–141 (2021).
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  5. Poljsak, B., Kovač, V., Milisav, I. Healthy Lifestyle Recommendations: Do the Beneficial Effects Originate from NAD+ Amount at the Cellular Level? Oxid Med Cell Longev. 2020 Dec 12;2020:8819627. doi: 10.1155/2020/8819627. PMID: 33414897; PMCID: PMC7752291.
  6. Chubanava, S., Treebak, J.T. Regular exercise effectively protects against the aging-associated decline in skeletal muscle NAD content. Experimental Gerontology, Volume 173, 2023,112109, ISSN 0531-5565.
  7. Juan, C.G., Matchett, K.B. & Davison, G.W. A systematic review and meta-analysis of the SIRT1 response to exercise. Sci Rep 13, 14752 (2023).
  8. Mouchiroud, L., Houtkooper, R.H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y.S., Viswanathan, M., Schoonjans, K., Guarente, L., Auwerx, J. The NAD+/Sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154.2 (2013): 430-441.
  9. Jacob R, Swenseid M. Niacin. In: Ziegler E, Filer L, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:185-190.

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