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Nicotinamide Adenine Dinucleotide (NAD): Difference between revisions
Nicotinamide Adenine Dinucleotide (NAD) (view source)
Revision as of 00:42, 20 December 2023
, 20 December 2023→NAD+, Sirtuins and Longevity-Promoting Pathway
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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. | 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. | ||
==NAD+ and Circadian Rhythm== | |||
NAD+ plays a vital role in regulating the circadian metabolic clock. Research has shown that older mice, with lower levels of NAD+, exhibit prolonged repression of CLOCK/BMAL1 transcription compared to younger mice with higher NAD+ levels, leading to disrupted and dampened mitochondrial and transcriptional oscillation{{pmid|32369735}}. Supplementation and restoration of NAD+ in circadian mutant mice have demonstrated the ability to re-establish proper respiratory oscillations and circadian metabolic regulation, especially through the regulatory activity of SIRT3{{pmid|24051248}}. An ample supply of NAD+ and proper sirtuin activation are essential for maintaining the integrity of various endogenous clocks. Supplementing with NAD+ precursors may potentially alleviate age-related disturbances in these circadian processes{{pmid|24657895}}. Deficiencies in NAD+ are observed in numerous age-related diseases, and NAD+-based interventions are being explored to address this common issue shared by these diseases{{pmid|34743990}}{{pmid|31953124}}{{pmid|29295624}}{{pmid|34720589}}. | |||
== See also == | == See also == | ||
* [[NAD+ Booster]] | * [[NAD+ Booster]] | ||