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Nicotinamide Mononucleotide (NMN) (view source)

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[[File:DALL·E_2023-10-14_05.01.46_-_A_photo_depicting_the_exact_instance_when_a_white_powdery_substance_is_spilling_from_a_tall,_elegant_white_packet._The_'NMN'_label_on_the_packet_is_sh.png|alt=A photo depicting the exact instance when a white powdery substance is spilling from a tall, elegant white packet. The 'NMN' label on the packet is sharply in focus.|right|frameless]]
[[File:DALL·E_2023-10-14_05.01.46_-_A_photo_depicting_the_exact_instance_when_a_white_powdery_substance_is_spilling_from_a_tall,_elegant_white_packet._The_'NMN'_label_on_the_packet_is_sh.png|alt=A photo depicting the exact instance when a white powdery substance is spilling from a tall, elegant white packet. The 'NMN' label on the packet is sharply in focus.|right|frameless]]
'''Nicotinamide Mononucleotide''' ('''NMN''' and '''β-NMN''') is a compound found naturally in the cells of our bodies and is integral to several cellular processes. NMN is a [[NAD+ Precursor|direct precursor]] to [[NAD+]], a vital coenzyme essential for a myriad of cellular functions. The levels of NAD+ are known to decline as we age, and this decline is associated with aging and various age-related diseases. The has been shown in several clinical trials that by supplementing with NMN, we can boost the levels of NAD+ in the body, potentially counteracting age-related cellular decline and improving overall health. Preliminary studies, mainly in mice, suggest that NMN supplementation could offer a range of health benefits, such as enhanced energy metabolism and improved DNA repair, indicating its potential role in slowing the aging processes.
'''Nicotinamide Mononucleotide''' ('''NMN''' and '''β-NMN''') is a compound found naturally in the cells of our bodies and is integral to several cellular processes. NMN is a [[NAD+ Precursor|direct precursor]] to [[NAD+]], a vital coenzyme essential for a myriad of cellular functions. The levels of NAD+ are known to decline as we age, and this decline is associated with aging and various age-related diseases. It has been shown in several clinical trials that by supplementing with NMN, we can boost the levels of NAD+ in the body, potentially counteracting age-related cellular decline and improving overall health. Preliminary studies, mainly in mice, suggest that NMN supplementation could offer a range of health benefits, such as enhanced energy metabolism and improved DNA repair, indicating its potential role in slowing the aging processes.


However, while NMN shows significant promise, comprehensive studies determining its long-term safety, effective dosage, and potential side effects in humans are still in progress. NMN is also present in several food sources, including broccoli, cabbage, cucumber, avocados, and edamame, but only in small quantities.
However, while NMN shows significant promise, comprehensive studies determining its long-term safety, effective dosage, and potential side effects in humans are still in progress. NMN is also present in several food sources, including broccoli, cabbage, cucumber, avocados, and edamame, but only in small quantities.
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! NMN Content (mg/100g-Food)
! NMN Content (mg/100g-Food)
|-
|-
| Vegetable
| rowspan="5" | Vegetable
| Edamame
| Edamame
| 0.47–1.88
| 0.47–1.88
|-
|-
| Vegetable
| Broccoli
| Broccoli
| 0.25–1.12
| 0.25–1.12
|-
|-
| Vegetable
| Cucumber Seed
| Cucumber Seed
| 0.56
| 0.56
|-
|-
| Vegetable
| Cucumber Peel
| Cucumber Peel
| 0.65
| 0.65
|-
|-
| Vegetable
| Cabbage
| Cabbage
| 0.0–0.90
| 0.0–0.90
|-
|-
| Fruit
| rowspan="2" | Fruit
| Avocado
| Avocado
| 0.36–1.60
| 0.36–1.60
|-
|-
| Fruit
| Tomato
| Tomato
| 0.26–0.30
| 0.26–0.30
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=== Bioavailability ===
=== Bioavailability ===
[[File:NMN NAD NAMN.png|thumb|Levels of NAD+ and NAMN in blood were increased by oral administration of 250mg NMN. NAD metabolome in blood was measured every 4 weeks. Three asterisks mean statistical significance: ''p''-value < 0.001.{{pmid|35479740}}]]
[[File:NMN NAD NAMN.png|thumb|Levels of NAD+ and NAMN in blood were increased by oral administration of 250mg NMN. NAD metabolome in blood was measured every 4 weeks. Three asterisks mean statistical significance: ''p''-value < 0.001.{{pmid|35479740}}|alt=Levels of NAD+ and NAMN in blood were increased by oral administration of 250mg NMN.]]
[[Bioavailability]] is a crucial factor in the effectiveness of any dietary supplement, including Nicotinamide Mononucleotide (NMN). It refers to the proportion of a substance that enters the circulation when introduced into the body and is thus able to have an active effect. In the case of NMN, bioavailability determines how much of the compound reaches the bloodstream and subsequently contributes to NAD+ biosynthesis.
[[Bioavailability]] is a crucial factor in the effectiveness of any dietary supplement, including Nicotinamide Mononucleotide (NMN). It refers to the proportion of a substance that enters the circulation when introduced into the body and is thus able to have an active effect. In the case of NMN, bioavailability determines how much of the compound reaches the bloodstream and subsequently contributes to NAD+ biosynthesis.
One of the main challenges with NMN bioavailability is its absorption and transportation within the body. When taken orally, NMN needs to be absorbed through the gastrointestinal tract, which can present barriers to its effective uptake.
One of the main challenges with NMN bioavailability is its absorption and transportation within the body. When taken orally, NMN needs to be absorbed through the gastrointestinal tract, which can present barriers to its effective uptake.
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=== Combination Therapy for Enhanced NAD+ Levels ===
A variety of nutritional supplements are available in the market, which contains the compositions of NMN coupled with natural products. Despite this, the synergistic effects and transformation processes of NMN in such combinations are not fully understood.
In a recent study, oral administration of NMN (500 mg/kg) was combined with either resveratrol (50 mg/kg) or ginsenosides (Rh2 & Rg3) (50 mg/kg) in [[C57BL/6 mice]] to assess the efficacy of these drug combinations. The results showed that the combination could increase NAD+ levels in specific mouse tissues compared to NMN alone:{{pmid|35844164}}
* '''With''' '''Resveratrol''': NAD+ levels increased approximately 1.6 times in the heart and 1.7 times in muscle tissue.
* '''With''' '''Ginsenosides (Rh2 & Rg3)''': NAD+ levels in lung tissue improved by about 2.0 times.
These findings suggest that combining NMN with specific natural products like resveratrol or ginsenosides may amplify the beneficial effects on NAD+ levels, offering new avenues for treating age-related diseases or conditions linked to decreased NAD+ levels in specific tissues.


=== Clearance ===
=== Clearance ===
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== Controversy about NMN as Direct Precursor ==
== Controversy about NMN as Direct Precursor ==
[[File:Mean plasma concentration–time profiles of NAD+ and NR in mice following oral NMN administration.png|thumb|NMN administration of NMN–HAP and free NMN increases plasma NAD+ and NR in mice{{pmid|37862582}}]]
[[File:Mean plasma concentration–time profiles of NAD+ and NR in mice following oral NMN administration.png|thumb|NMN administration of NMN–HAP and free NMN increases plasma NAD+ and NR in mice{{pmid|37862582}}|alt=NMN administration of NMN–HAP and free NMN increases plasma NAD+ and NR in mice]]
NMN is often advertised, for example by NMN suppliers, as a direct precursor to NAD+, purportedly making it more effective compared to other precursors like '''Nicotinamide Riboside (NR)'''. However, NMN's role as a direct precursor is only effective when it is '''inside the cell'''. This raises questions about how NMN, when ingested or administered externally, enters the cell to contribute to NAD+ synthesis. The central controversy surrounding NMN as a precursor to NAD+ lies in its mechanism of cellular entry. While NMN is a direct precursor of NAD+ within the cell, the debate focuses on whether NMN can be directly absorbed by cells or if it must first be converted to NR. In that case, NR might have an advantage over NMN, as NMN would require one additional conversion step compared to NR.
NMN is often advertised, for example by NMN suppliers, as a direct precursor to NAD+, purportedly making it more effective compared to other precursors like '''Nicotinamide Riboside (NR)'''. However, NMN's role as a direct precursor is only effective when it is '''inside the cell'''. This raises questions about how NMN, when ingested or administered externally, enters the cell to contribute to NAD+ synthesis. The central controversy surrounding NMN as a precursor to NAD+ lies in its mechanism of cellular entry. While NMN is a direct precursor of NAD+ within the cell, the debate focuses on whether NMN can be directly absorbed by cells or if it must first be converted to NR. In that case, NR might have an advantage over NMN, as NMN would require one additional conversion step compared to NR.


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===Stilbenes: Resveratrol and Pterostilbene===
===Stilbenes: Resveratrol and Pterostilbene===
Stilbenes, particularly [[Resveratrol|resveratrol]] and [[Pterostilbene|pterostilbene]], are non-flavonoid phenolic compounds extensively studied for their anti-inflammatory, antioxidant properties, and their role in combating age-related disorders like diabetes and cancer{{pmid|23448440}}{{doi|10.7324/JAPS.2019.90717|Chan EWC, Wong CW, Tan YH, Foo JPY, Wong SK, Chan HT. Resveratrol and pterostilbene: A comparative overview of their chemistry, biosynthesis, plant sources and pharmacological properties. J Appl Pharm Sci, 2019; 9(07):124–129.}}. They are found naturally in grapes and berries, and studies have established their safety and bioavailability, with doses of resveratrol up to 5 grams and pterostilbene to 250 mg being well-tolerated{{pmid|23431291}}{{pmid|30513922}}.
Stilbenes, particularly [[Resveratrol|resveratrol]] and [[Pterostilbene|pterostilbene]], are non-flavonoid phenolic compounds extensively studied for their anti-inflammatory, [[Antioxidant|antioxidant]] properties, and their role in combating age-related disorders like diabetes and cancer{{pmid|23448440}}{{doi|10.7324/JAPS.2019.90717|Chan EWC, Wong CW, Tan YH, Foo JPY, Wong SK, Chan HT. Resveratrol and pterostilbene: A comparative overview of their chemistry, biosynthesis, plant sources and pharmacological properties. J Appl Pharm Sci, 2019; 9(07):124–129.}}. They are found naturally in grapes and berries, and studies have established their safety and bioavailability, with doses of resveratrol up to 5 grams and pterostilbene to 250 mg being well-tolerated{{pmid|23431291}}{{pmid|30513922}}.


Despite their potential, resveratrol and pterostilbene have shown lifespan extension only in certain preclinical models, with the results being context-dependent and subject to debate{{pmid|29210129}}. Pterostilbene is particularly notable for its higher bioavailability (80%) compared to resveratrol (20%), and its efficacy in upregulating antioxidant enzymes like SOD and GR{{pmid|23691264}}. This difference in bioavailability is critical in modulating the SIRT1 pathway, with co-administration of the two potentially maximizing their collective benefits{{pmid|18826454}}.
Despite their potential, resveratrol and pterostilbene have shown lifespan extension only in certain preclinical models, with the results being context-dependent and subject to debate{{pmid|29210129}}. Pterostilbene is particularly notable for its higher bioavailability (80%) compared to resveratrol (20%), and its efficacy in upregulating antioxidant enzymes like SOD and GR{{pmid|23691264}}. This difference in bioavailability is critical in modulating the SIRT1 pathway, with co-administration of the two potentially maximizing their collective benefits{{pmid|18826454}}.
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=== CoQ10 ===
=== CoQ10 ===
[[Coenzyme Q10 (CoQ10)]], also known as ubiquinol in its oxidized form, ubiquinone, is a crucial component in the mitochondrial electron transport chain. Its role in cellular energy production and as an antioxidant makes it integral to health, particularly in the context of neurodegenerative disorders, diabetes, cancer, fibrosis, and cardiovascular diseases{{pmid|25126052}}. CoQ10 supplementation, especially in disease states, is aimed at restoring antioxidant activity to correct homeostatic imbalances{{pmid|24389208}}.
[[Coenzyme Q10 (CoQ10)]], also known as ubiquinol in its oxidized form, ubiquinone, is a crucial component in the mitochondrial electron transport chain. Its role in cellular energy production and as an [[Antioxidant|antioxidant]] makes it integral to health, particularly in the context of neurodegenerative disorders, diabetes, cancer, fibrosis, and cardiovascular diseases{{pmid|25126052}}. CoQ10 supplementation, especially in disease states, is aimed at restoring antioxidant activity to correct homeostatic imbalances{{pmid|24389208}}.


CoQ10's cardiovascular protective qualities are well-established, with evidence showing its ability to improve hyperglycemia, hypertension, oxidative stress, and reduce the risk of cardiac events{{pmid|32331285}}. Notably, endogenous synthesis of CoQ10 declines with age, and higher mitochondrial levels have been linked to increased longevity. This connection is particularly evident in skeletal muscle health in the elderly, where higher plasma CoQ10 content correlates with improved muscle integrity and reduced levels of inflammatory markers such as TNF-α, IL-6, and CRP{{pmid|29459830}}.
CoQ10's cardiovascular protective qualities are well-established, with evidence showing its ability to improve hyperglycemia, hypertension, oxidative stress, and reduce the risk of cardiac events{{pmid|32331285}}. Notably, endogenous synthesis of CoQ10 declines with age, and higher mitochondrial levels have been linked to increased longevity. This connection is particularly evident in skeletal muscle health in the elderly, where higher plasma CoQ10 content correlates with improved muscle integrity and reduced levels of inflammatory markers such as TNF-α, IL-6, and CRP{{pmid|29459830}}.
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Flavonoids such as fisetin, quercetin, luteolin/luteolinidin, and apigenin have demonstrated significant health benefits, including potent senolytic activity.
Flavonoids such as fisetin, quercetin, luteolin/luteolinidin, and apigenin have demonstrated significant health benefits, including potent senolytic activity.


'''[[Fisetin]]''' and '''[[Quercetin|quercetin]]''' are known for their anti-cancer properties, particularly in inducing calcium-induced tumor apoptosis and improving cancer-related inflammatory profiles{{pmid|31064104}}. Fisetin, in particular, has shown strong senolytic effects in older and progeroid mice models, as well as in murine and human adipose tissues, contributing to improved lifespan and tissue homeostasis{{pmid|30279143}}. Its safety and efficacy are being investigated in Phase 2 clinical trials focusing on reducing inflammation and improving walking speed in frail elderly individuals (NCT03675724, NCT03430037). Fisetin also interacts with the NAD+/NADH age-related pathway, notably through SIRT1 activation, suggesting potential geroprotective effects in the context of NAD+/SIRT1/CD38 pathways, although more research is needed to establish concrete effects on longevity{{pmid|22493485}}.
'''[[Fisetin]]''' and '''[[Quercetin|quercetin]]''' are known for their anti-cancer properties, particularly in inducing calcium-induced tumor [[Apoptosis|apoptosis]] and improving cancer-related inflammatory profiles{{pmid|31064104}}. Fisetin, in particular, has shown strong senolytic effects in older and progeroid mice models, as well as in murine and human adipose tissues, contributing to improved lifespan and tissue homeostasis{{pmid|30279143}}. Its safety and efficacy are being investigated in Phase 2 clinical trials focusing on reducing inflammation and improving walking speed in frail elderly individuals (NCT03675724, NCT03430037). Fisetin also interacts with the NAD+/NADH age-related pathway, notably through SIRT1 activation, suggesting potential geroprotective effects in the context of NAD+/SIRT1/CD38 pathways, although more research is needed to establish concrete effects on longevity{{pmid|22493485}}.


Quercetin, structurally similar to fisetin, is also recognized as a senolytic agent with benefits in cardiovascular disease, neurodegeneration, inflammation, oxidative stress, cancer, and diabetes management. It is considered a geroprotective agent in in vitro models of premature aging{{pmid|35458696}}{{pmid|30069858}}. Quercetin contributes to the modulation of the NAD+/SIRT1/CD38 axis by altering the NAD+/NADH ratio, activating SIRT1, and inhibiting CD38, thereby impacting metabolic disorders{{pmid|23172919}}{{pmid|33200005}}{{pmid|16395647}}.
Quercetin, structurally similar to fisetin, is also recognized as a senolytic agent with benefits in cardiovascular disease, neurodegeneration, inflammation, oxidative stress, cancer, and diabetes management. It is considered a geroprotective agent in in vitro models of premature aging{{pmid_warn|35458696}}{{pmid_warn|30069858}}. Quercetin contributes to the modulation of the NAD+/SIRT1/CD38 axis by altering the NAD+/NADH ratio, activating SIRT1, and inhibiting CD38, thereby impacting metabolic disorders{{pmid|23172919}}{{pmid|33200005}}{{pmid|16395647}}.


'''Luteolin''' and its derivative '''luteolinidin''' have shown anti-inflammatory effects, particularly in skin aging, skin diseases, and cognitive functions{{pmid|33368702}}. They are implicated in the CD38 mechanism, acting as potent inhibitors and leading to an increase in available NAD+ levels{{pmid|21641214}}{{pmid|28108596}}. Their potential in clearing cellular senescence, especially when used alongside NAD+ supporting compounds, highlights their role in longevity promotion{{pmid|34699859}}.
'''Luteolin''' and its derivative '''luteolinidin''' have shown anti-inflammatory effects, particularly in skin aging, skin diseases, and cognitive functions{{pmid|33368702}}. They are implicated in the CD38 mechanism, acting as potent inhibitors and leading to an increase in available NAD+ levels{{pmid|21641214}}{{pmid|28108596}}. Their potential in clearing cellular senescence, especially when used alongside NAD+ supporting compounds, highlights their role in longevity promotion{{pmid|34699859}}.


'''[[Apigenin]]''', derived from parsley and chamomile, exhibits strong anti-inflammatory, antioxidant, and anti-carcinogenic properties. It reduces inflammatory mediators like COX2, IL6, and TNF-α{{pmid|26180592}}, and upregulates antioxidant enzymes such as SOD, GPX, and GR{{doi|10.1080/10942912.2016.1207188}}. Apigenin's anti-cancer activity is evident in its ability to downregulate key cancer pathways and sensitize tumor cells to chemotherapy{{pmid|33333052}}. It also attenuates metabolic complications and possesses anti-obesity effects{{pmid|34679777}}{{pmid|28971573}}{{pmid|31877350}}. Additionally, apigenin improves vascular endothelial function and structure, counteracting age-related changes due to oxidative stress{{pmid|34114892}}.
'''[[Apigenin]]''', derived from parsley and chamomile, exhibits strong anti-inflammatory, [[Antioxidant|antioxidant]], and anti-carcinogenic properties. It reduces inflammatory mediators like COX2, IL6, and TNF-α{{pmid|26180592}}, and upregulates antioxidant enzymes such as SOD, GPX, and GR{{doi|10.1080/10942912.2016.1207188}}. Apigenin's anti-cancer activity is evident in its ability to downregulate key cancer pathways and sensitize tumor cells to chemotherapy{{pmid|33333052}}. It also attenuates metabolic complications and possesses anti-obesity effects{{pmid|34679777}}{{pmid|28971573}}{{pmid|31877350}}. Additionally, apigenin improves vascular endothelial function and structure, counteracting age-related changes due to oxidative stress{{pmid|34114892}}.


In the context of NAD+ supplementation, apigenin’s involvement with the SIRT1, NAD+, and CD38 axis is particularly notable. It enhances endogenous NAD+ levels by inhibiting CD38 and increasing the activation ratio of SIRT1 and NAD+/NADH, thereby reducing cellular senescence due to oxidative stress{{pmid|34049472}}{{pmid|32507768}}. This strong inhibition of CD38 by apigenin makes it an integral part of strategies aimed at restoring age-related depletion of NAD+ levels, enhancing the effectiveness of NMN supplementation and overall geroprotective strategies.
In the context of NAD+ supplementation, apigenin’s involvement with the SIRT1, NAD+, and CD38 axis is particularly notable. It enhances endogenous NAD+ levels by inhibiting CD38 and increasing the activation ratio of SIRT1 and NAD+/NADH, thereby reducing cellular senescence due to oxidative stress{{pmid|34049472}}{{pmid|32507768}}. This strong inhibition of CD38 by apigenin makes it an integral part of strategies aimed at restoring age-related depletion of NAD+ levels, enhancing the effectiveness of NMN supplementation and overall geroprotective strategies.


=== Carotenoids: Astaxanthin and Lycopene ===
=== Carotenoids: Astaxanthin and Lycopene ===
Carotenoids like astaxanthin and lycopene are renowned for their antioxidant and anti-inflammatory properties, playing a significant role in health and longevity (Figure 2).
Carotenoids like astaxanthin and lycopene are renowned for their [[Antioxidant|antioxidant]] and anti-inflammatory properties, playing a significant role in health and longevity (Figure 2).


'''Astaxanthin''' is a powerful antioxidant carotenoid known for its ability to mitigate reactive oxygen species (ROS) and support mitochondrial integrity{{pmid|31814873}}. It has shown remarkable efficacy in activating SIRT1, which contributes to its longevity-promoting effects:
'''Astaxanthin''' is a powerful antioxidant carotenoid known for its ability to mitigate reactive oxygen species (ROS) and support mitochondrial integrity{{pmid|31814873}}. It has shown remarkable efficacy in activating SIRT1, which contributes to its longevity-promoting effects:
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* '''Boosting NAD+ Levels''': Notably, a study combining NMN, astaxanthin, and blood orange extract in aging zebrafish demonstrated an enhanced ability to raise NAD+ levels, surpassing combinations of NR with astaxanthin or pterostilbene{{doi|10.1093/cdn/nzac047.054}}. This finding suggests astaxanthin's potential in NAD+ boosting strategies and warrants further research on effective dosages and combinations in humans.
* '''Boosting NAD+ Levels''': Notably, a study combining NMN, astaxanthin, and blood orange extract in aging zebrafish demonstrated an enhanced ability to raise NAD+ levels, surpassing combinations of NR with astaxanthin or pterostilbene{{doi|10.1093/cdn/nzac047.054}}. This finding suggests astaxanthin's potential in NAD+ boosting strategies and warrants further research on effective dosages and combinations in humans.


'''Lycopene''' is another carotenoid with significant antioxidant and anti-inflammatory effects. It is known for improving various age-related conditions:
'''Lycopene''' is another carotenoid with significant [[Antioxidant|antioxidant]] and anti-inflammatory effects. It is known for improving various age-related conditions:


* '''Physical Performance and Skin Aging''': Supplementation with lycopene has been shown to enhance physical performance, combat osteoporosis, and improve skin aging, owing to its antioxidant properties{{pmid|26881023}}.
* '''Physical Performance and Skin Aging''': Supplementation with lycopene has been shown to enhance physical performance, combat osteoporosis, and improve skin aging, owing to its antioxidant properties{{pmid|26881023}}.
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* '''Cardiovascular Health''': Curcumin's impact on cardiovascular health is highlighted by its ability to activate AMPK, another significant pathway in aging and metabolic regulation{{pmid|30145851}}.
* '''Cardiovascular Health''': Curcumin's impact on cardiovascular health is highlighted by its ability to activate AMPK, another significant pathway in aging and metabolic regulation{{pmid|30145851}}.
* '''Anti-cancer Properties''': Experimental models of head and neck squamous cell carcinoma have shown that curcumin can inhibit cancer cell migration and angiogenesis, underscoring its anti-cancer potential{{pmid|26299580}}.
* '''Anti-cancer Properties''': Experimental models of head and neck squamous cell carcinoma have shown that curcumin can inhibit cancer cell migration and angiogenesis, underscoring its anti-cancer potential{{pmid|26299580}}.
* '''Physical Performance''': A six-week supplementation with curcumin in human runners has led to improvements in antioxidant capacity and aerobic performance. This benefit is accompanied by an increase in SIRT3, a mitochondrial protein linked to energy metabolism{{pmid|36125053}}.
* '''Physical Performance''': A six-week supplementation with curcumin in human runners has led to improvements in [[Antioxidant|antioxidant]] capacity and aerobic performance. This benefit is accompanied by an increase in SIRT3, a mitochondrial protein linked to energy metabolism{{pmid|36125053}}.


The relationship between curcumin and sirtuins, particularly in the context of NAD+ boosting, is a promising area of research. However, the effectiveness of combining curcumin with NAD+ enhancing supplements needs to be explored further in clinical trials. Such studies would help establish whether curcumin can augment the benefits of NAD+ precursors, potentially leading to more effective anti-aging therapies.
The relationship between curcumin and sirtuins, particularly in the context of NAD+ boosting, is a promising area of research. However, the effectiveness of combining curcumin with NAD+ enhancing supplements needs to be explored further in clinical trials. Such studies would help establish whether curcumin can augment the benefits of NAD+ precursors, potentially leading to more effective anti-aging therapies.
===Alpha-Ketoglutarate===
Alpha-ketoglutarate (aKG) is a critical metabolic intermediate in the Krebs cycle, playing an important role in the aging process{{pmid|32877686}}. Its involvement in various longevity-related mechanisms makes it a significant compound in geroprotection and anti-aging research.
*'''Inhibition of the TOR Pathway''': aKG is known to inhibit the TOR pathway, akin to the effects of caloric restriction. This inhibition, coupled with its ability to hinder ATP synthase, has been shown to extend the lifespan in ''C. elegans''{{pmid|24828042}}.
*'''Metabolic and Antioxidant Benefits''': Providing both metabolic and [[Antioxidant|antioxidant]] benefits, aKG has been demonstrated to extend lifespan. This effect is evident not only in model organisms but also in mice. Recent pilot clinical trials have indicated that Rejuvant, a novel formulation of aKG, effectively reduces biological age in humans{{pmid|33340716}}{{pmid|34847066}}{{pmid|32877690}}.
*'''Interplay with NAD+''': The relationship between aKG and NAD+, a vital coenzyme for cellular health and aging, remains under-researched. Future studies should explore this interaction to enhance our understanding of how aKG can be utilized in longevity therapies.
The potential of aKG in anti-aging strategies is promising, but more research is necessary to fully understand its interactions, particularly with NAD+.
===Epigallocatechin Gallate===
The polyphenol epigallocatechin gallate (EGCG; Figure 2), predominantly found in green tea, is renowned for its neuroprotective, [[Antioxidant|antioxidant]], and anti-inflammatory properties. Current research is investigating its role in alleviating a variety of diseases{{pmid|35327563}}. EGCG's interaction with aging and longevity pathways is particularly noteworthy.
*'''Lifespan Extension''': EGCG has been shown to increase lifespan in response to oxidative stress, as evidenced by studies in rats demonstrating enhanced longevity under such conditions{{pmid|23834676}}.
*'''SIRT1 Modulation''': The effect of EGCG on SIRT1, a crucial protein in aging and metabolism, appears to vary depending on the context. Some studies have observed an upregulation of SIRT1 following EGCG administration{{pmid|33371812}}, while others have reported a downregulation, especially in cancer cells{{pmid|23881751}}{{pmid|35548580}}. This suggests that EGCG's impact on SIRT1 may differ based on specific biological factors and the need for upregulation of longevity pathways in response to oxidative stress.
*'''NAD+/NADH Ratio Effects''': The influence of EGCG on the NAD+/NADH ratio, vital for cellular metabolism and aging, requires further investigation. Understanding how EGCG affects this ratio is essential for comprehending its potential as an anti-aging agent and its role in cellular health maintenance.
The diverse effects of EGCG on SIRT1 and the NAD+/NADH ratio underline the importance of more detailed research to clarify its mechanisms of action, particularly regarding longevity and age-related diseases.
==Clinical Trials==
==Clinical Trials==
Starting in 2020, with the assessment of the safety of a single dose administration of NMN, there have been around 10 randomized controlled trials (RCTs) exploring the compound's effects in various contexts. The trials have varied in duration, with the longest running for 12 weeks. In terms of dosage, they have explored a range of quantities, with the highest being 1,250 mg of NMN per day and 2,000 mg (2 g) of MIB-626, a specific formulation of NMN, per day. The following table provides a comprehensive overview of these trials, detailing their design, participant demographics, dosages, and key findings:
Starting in 2020, with the assessment of the safety of a single dose administration of NMN, there have been around 10 randomized controlled trials (RCTs) exploring the compound's effects in various contexts. The trials have varied in duration, with the longest running for 12 weeks. In terms of dosage, they have explored a range of quantities, with the highest being 1,250 mg of NMN per day and 2,000 mg (2 g) of MIB-626, a specific formulation of NMN, per day. The following table provides a comprehensive overview of these trials, detailing their design, participant demographics, dosages, and key findings:
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|-
|-
|{{pmid_text|35182418}}
|{{pmid_text|35182418}}
* [https://www.nmn.com/news/nmn-tablet-blood-nad-levels-humans NMN.com article]
|[[RCT]], 2 weeks
|[[RCT]], 2 weeks
*1000 mg MIB-626
*1000 mg MIB-626
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*[[Nicotinamide Adenine Dinucleotide (NAD+)]]
*[[Nicotinamide Adenine Dinucleotide (NAD+)]]
*[[Nicotinamide Riboside (NR)]]
*[[NAD+ Boosters]]
*[[NAD+ Boosters]]
*[[NAD+ Precursor]]
*[[NAD+ Precursor]]
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==Todo==
==Todo==


*{{pmid_text|36678315}}
*{{pmid text|38191197}}
**{{pmid text|35844164}}
*{{pmid text|38064810}}
*{{pmid text|30216853}}
*{{pmid text|37273100}}
*https://www.nmn.com/news/nmn-tablet-blood-nad-levels-humans
*https://link.springer.com/article/10.1007/s13668-023-00475-y
*https://www.lifespan.io/topic/nmn-nicotinamide-mononucleotide-benefits-side-effects/
*https://www.lifespan.io/topic/nmn-nicotinamide-mononucleotide-benefits-side-effects/
*https://novoslabs.com/frequently-asked-questions/nmn-nicotinamide-mononucleotide/can-you-take-nmn-if-you-have-a-mthfr-mutation-or-suffer-from-reduced-methylation/
*https://novoslabs.com/frequently-asked-questions/nmn-nicotinamide-mononucleotide/can-you-take-nmn-if-you-have-a-mthfr-mutation-or-suffer-from-reduced-methylation/
*https://ajtm.journals.publicknowledgeproject.org/index.php/ajtm/article/view/2535
*https://ajtm.journals.publicknowledgeproject.org/index.php/ajtm/article/view/2535
*https://www.nature.com/articles/s41598-018-30792-0
*https://www.nature.com/articles/s41598-018-30792-0
*https://www.nmn.com/news/new-study-shows-nmn-rejuvenates-stem-cells-and-mitochondria-by-activating-longevity-protein
*https://www.nmn.com/news/new-study-shows-nmn-rejuvenates-stem-cells-and-mitochondria-by-activating-longevity-protein  


{{pmid text|36499074}}
{{pmid text|36499074}}
* https://www.nmn.com/news/combining-nmn-and-prebiotics-to-counter-cognitive-decline
*Slc12a8
*Slc12a8
**{{pmid text|33353981}}
**{{pmid text|33353981}}
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==References==
==References==
<references />
<references />
[[Category:Orally Consumable Longevity Compounds]]
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