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Nicotinamide Adenine Dinucleotide (NAD): Difference between revisions
Nicotinamide Adenine Dinucleotide (NAD) (view source)
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NAD exists in two main forms: NAD+ and NADH. NAD+ is the oxidized form of the compound and is essential for various cellular processes, including DNA repair, gene expression, and calcium signaling. When NAD+ accepts electrons during metabolic reactions, it becomes reduced and transforms into NADH. NADH, the reduced form, primarily functions in the production of ATP, the cell's primary energy currency, through the electron transport chain. The dynamic interconversion between these two forms, NAD+ and NADH, is fundamental to the cell's energy production and overall function. | NAD exists in two main forms: NAD+ and NADH. NAD+ is the oxidized form of the compound and is essential for various cellular processes, including DNA repair, gene expression, and calcium signaling. When NAD+ accepts electrons during metabolic reactions, it becomes reduced and transforms into NADH. NADH, the reduced form, primarily functions in the production of ATP, the cell's primary energy currency, through the electron transport chain. The dynamic interconversion between these two forms, NAD+ and NADH, is fundamental to the cell's energy production and overall function. | ||
== The Role of NAD+ in the Cell == | |||
NAD+ is involved in several crucial biological processes: | NAD+ is involved in several crucial biological processes: | ||
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[[File:nihms790132f7.jpg|thumb|[[CD38]]/[[NADase]] increases during aging, and causes NAD decline and subsequent mitochondrial dysfunction.]] | [[File:nihms790132f7.jpg|thumb|[[CD38]]/[[NADase]] increases during aging, and causes NAD decline and subsequent mitochondrial dysfunction.]] | ||
== NAD+ Decline with Age == | |||
A significant finding in the field of aging research is that NAD+ levels naturally decline as we age. This reduction has been associated with: | A significant finding in the field of aging research is that [[NAD+]] levels naturally decline as we age. This reduction has been associated with: | ||
* A decrease in mitochondrial function, leading to reduced energy output. | * A decrease in mitochondrial function, leading to reduced energy output. | ||
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* Enhanced vulnerability of DNA to damage. | * Enhanced vulnerability of DNA to damage. | ||
* Increased susceptibility to age-related diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. | * Increased susceptibility to age-related diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. | ||
A gradual increase in CD38 has been implicated in the decline of | A gradual increase in CD38 has been implicated in the decline of NAD+ with age.<ref>Camacho-Pereira J, Tarragó MG, Chini CC, Nin V, Escande C, Warner GM, Puranik AS, Schoon RA, Reid JM, Galina A, Chini EN (June 2016). "CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism". ''Cell Metabolism''. '''23''' (6): 1127–1139. doi:10.1016/j.cmet.2016.05.006. PMC 4911708. PMID 27304511.</ref><ref>Schultz MB, Sinclair DA (June 2016). "Why NAD(+) Declines during Aging: It's Destroyed". ''Cell Metabolism''. '''23''' (6): 965–966. doi:10.1016/j.cmet.2016.05.022. PMC 5088772. PMID 27304496.</ref> Treatment of old mice with a specific [[CD38]] inhibitor, [[78c]], prevents age-related NAD+ decline.<ref>Tarragó MG, Chini CC, Kanamori KS, Warner GM, Caride A, de Oliveira GC, Rud M, Samani A, Hein KZ, Huang R, Jurk D, Cho DS, Boslett JJ, Miller JD, Zweier JL, Passos JF, Doles JD, Becherer DJ, Chini EN (May 2018). "A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline". ''Cell Metabolism''. '''27''' (5): 1081–1095.e10. doi:10.1016/j.cmet.2018.03.016. PMC 5935140. PMID 29719225.</ref> CD38 knockout mice have twice the levels of NAD+ and are resistant to age-associated NAD+ decline,<ref name="pmid32595066">Cambronne XA, Kraus WL (2020). "Location, Location, Location: Compartmentalization of NAD + Synthesis and Functions in Mammalian Cells". ''Trends in Biochemical Sciences''. '''45''' (10): 858–873. doi:10.1016/j.tibs.2020.05.010. PMC 7502477. PMID 32595066.</ref> with dramatically increased NAD+ levels in major organs (liver, muscle, brain, and heart).<ref name="pmid32594513">Kang BE, Choi J, Stein S, Ryu D (2020). "Implications of NAD + boosters in translational medicine". ''European Journal of Clinical Investigation''. '''50''' (10): e13334. doi:10.1111/eci.13334. PMID 32594513. S2CID 220254270.</ref> On the other hand, mice overexpressing CD38 exhibit reduced NAD+ and mitochondrial dysfunction.<ref name="pmid32595066" /> | ||
== Boosting NAD+ Levels == | |||
Given the importance of NAD+ in various cellular functions and its decline with age, researchers have been exploring ways to replenish or boost NAD+ levels in the body. Several methods are under investigation: | Given the importance of NAD+ in various cellular functions and its decline with age, researchers have been exploring ways to replenish or boost NAD+ levels in the body. Several methods are under investigation: | ||
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{{See|NAD+ Booster}} | {{See|NAD+ Booster}} | ||
== Safety and Implications for Longevity == | |||
While initial studies, primarily on animal models, have shown promise in boosting NAD+ levels for promoting health and extending lifespan, it's essential to approach the findings with caution. Comprehensive human trials are needed to understand: | While initial studies, primarily on animal models, have shown promise in boosting NAD+ levels for promoting health and extending lifespan, it's essential to approach the findings with caution. Comprehensive human trials are needed to understand: | ||
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* [[NAD+ Precursor]] | * [[NAD+ Precursor]] | ||
* [[NADase]] | * [[NADase]] | ||
* | * {{SeeWikipedia|Nicotinamide adenine dinucleotide}} | ||
== Todo == | == Todo == | ||