Nicotinamide Adenine Dinucleotide (NAD): Difference between revisions

Nicotinamide Adenine Dinucleotide (NAD) (view source)

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 * The real impact on human longevity.
+== NAD+, Sirtuins and Longevity-Promoting Pathway ==
+[[File:CD38-NAD+-SIRT1 Axis.png|thumb|The CD38/NAD+/SIRT1 Axis. NAD+ levels in the body can be influenced by the supplementation of precursors nicotinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). NAD+ levels decrease with age and are further metabolized by the activation of SIRT1, PARP1, SARM1, and CD38. Restoring NAD+ levels allows for an increase in SIRT1 activity due to increased substrate availability, resulting in the inhibition of age-promoting pathways and activation of adaptive and protective transcription factors and processes. The central lineage may be described as the CD38/NAD+/SIRT1 axis, and targeting this access with nutraceutical interventions may prevent the age-related decline of NAD+ levels in the body. Black lines indicate conversion or activation. Red lines indicate inhibitors or destroyers of the indicated target.{{pmid|36678315}}]]
+Disruption of proper NAD+ levels and the loss of protective sirtuin activity have emerged as prime targets for NAD+-based interventions{{pmid|28537485}}. Administration of NAD+ precursors, such as Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), has shown potential in alleviating age-related NAD+ decline and associated pathologies, particularly in the context of age-related diseases{{pmid|28899755}}{{pmid|29883761}}{{pmid|27825999}}. Aging is associated with a decreased NAD+/NADH ratio in human plasma, mainly due to the deterioration of NAD+ stores, rather than an increase in NADH{{pmid|30124109}}. Replenishing NAD+ has been shown to rescue mitochondrial regulatory function from NAD+ induced pseudohypoxic mitochondrial stress during aging{{pmid|24360282}}.
+SIRT1, a member of the sirtuin protein family involved in cellular response to stress, has been implicated in longevity, although results are mixed and context-dependent. High-level athletes, for instance, exhibit higher telomere length and reduced insulin resistance, correlating with higher levels of SIRT1 expression{{pmid|34256387}}. SIRT1's beneficial activity may depend on the deacetylation and activation of Forkhead transcription factors like FoxO and PGC1α{{pmid|26831453}}{{pmid|14976264}}. FoxOs are involved in stress resistance, cell cycle arrest, apoptosis, and tumor suppression, and their activation has been linked with longevity in worms and flies{{pmid|16288288}}{{pmid|35004893}}. The insulin/insulin-like growth factor signaling (IIS) pathway, which regulates growth, development, metabolism, reproduction, and longevity, extends neuronal activity and longevity under low IIS conditions through FoxO activity{{pmid|26675724}}{{pmid|21443682}}. PGC1α, influencing mitochondrial biogenesis, is important in metabolic diseases, and its overexpression has been linked to improved insulin sensitivity in muscle{{pmid|23583953}}{{pmid|24559845}}{{pmid|23086035}}. Additionally, AMPK, involved in energy expenditure, exhibits a bidirectional interplay with SIRT1 and inhibits mTOR, a process linked to longevity; it also activates SIRT1 by increasing available NAD+ stores{{pmid|19262508}}. Furthermore, nuclear factor κB (NF-κB) signaling, involved in innate immunity, can be inhibited by SIRT1 activity to reduce prolonged inflammatory signaling{{pmid|23770291}}. The availability of NAD+ in the body makes SIRT1 an interesting target in manipulating age-related pathways to promote longevity{{pmid|29883761}}{{pmid|33460497}}{{pmid|33609766}}{{pmid|32124104}}. Maintaining adequate NAD+ levels for optimal SIRT1 activity during aging may be a key factor in regulating longevity.
 == See also ==
 * [[NAD+ Booster]]