2,851
edits
Nicotinamide Adenine Dinucleotide (NAD): Difference between revisions
Nicotinamide Adenine Dinucleotide (NAD) (view source)
Revision as of 00:37, 20 December 2023
, 20 December 2023→Safety and Implications for Longevity
| Line 37: | Line 37: | ||
* The effective dosages and potential side effects. | * The effective dosages and potential side effects. | ||
* The real impact on human longevity. | * The real impact on human longevity. | ||
==NAD+ and Aging-Related Enzymes== | |||
Nicotinamide adenine dinucleotide (NAD+) is a key coenzyme in metabolic processes, playing roles in energy expenditure, metabolic and stress adaptations, and circadian rhythm maintenance. A significant decline in NAD+ levels with age can be attributed to CD38, an enzyme responsible for NAD+ degradation, disrupting NAD+ synthesis pathways during aging{{pmid|27304496}}. NAD+ homeostasis is critical for optimal biological function, with NAD+ consuming enzymes playing specific roles in biological aging. They are potential targets for geroprotection, including CD38, the sirtuins (SIRT) deacetylases, poly [ADP-ribose] polymerase 1 (PARP1, involved in DNA damage response), and the neuronal degenerating factor SARM1{{pmid|28676700}}{{pmid|25908823}}. | |||
NAD+ can be synthesized de novo from nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), or salvaged through the NAD+ salvage pathway, crucial for recycling metabolites to replete NAD+ stores{{pmid|32694684}}. An extracellular conversion of NMN to NR by CD73, a cell surface enzyme, also helps maintain intracellular NAD+ content{{pmid|32389638}}. | |||
===Nicotinamide N-Methyltransferase (NNMT) and Its Role=== | |||
Nicotinamide N-methyltransferase (NNMT) regulates cellular NAD+ levels by methylating nicotinamide into methylnicotinamide (MNT), reducing free nicotinamide availability for NAD+ conversion through the NAD+ salvage pathway. NNMT and MNT are associated with conditions like obesity and type two diabetes mellitus{{pmid|29483571}}. Interestingly, NNMT stabilizes SIRT1, offering metabolic benefits and protection against oxidative stress-induced cellular injury{{pmid|34153425}}{{pmid|26168293}}. Methylnicotinamide has been shown to increase lifespan{{pmid|24077178}}. Furthermore, various NNMT inhibitors have been developed, showing potential in treating pathological states like cancer, metabolic disorders, and alcohol-related fatty liver disease{{pmid|29483571}}{{pmid|34704059}}{{pmid|34572571}}{{pmid|29155147}}{{pmid|34424711}}. The interaction between NNMT, MNT, and their regulatory pathways plays a significant role in NAD+ homeostasis and the complex disease states affecting the aging process. | |||
== NAD+, Sirtuins and Longevity-Promoting Pathway == | == 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}}|450x450px]] | [[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}}|450x450px]] | ||