2,851
edits
Nicotinamide Mononucleotide (NMN): Difference between revisions
Nicotinamide Mononucleotide (NMN) (view source)
Revision as of 23:49, 19 December 2023
, 19 December 2023→3.3. Trimethylglycine (TMG)
| Line 320: | Line 320: | ||
The antioxidant, anti-inflammatory, and age-mitigating effects of CoQ10 position it as a valuable supplement in an orthomolecular approach to combat the biological process of aging. This is especially true when considering its supportive role in enhancing NAD+ levels. However, further research is needed to fully elucidate the synergistic benefits of combining NAD+ precursors with CoQ10 supplementation in aging and age-related diseases. | The antioxidant, anti-inflammatory, and age-mitigating effects of CoQ10 position it as a valuable supplement in an orthomolecular approach to combat the biological process of aging. This is especially true when considering its supportive role in enhancing NAD+ levels. However, further research is needed to fully elucidate the synergistic benefits of combining NAD+ precursors with CoQ10 supplementation in aging and age-related diseases. | ||
=== | === Trimethylglycine (TMG) === | ||
[[Trimethylglycine (TMG)]], also known as betaine, was initially derived from the beetroot plant and is recognized for its osmoprotectant and anti-inflammatory properties. As a primary methyl group donor, TMG plays a significant role in DNA methylation processes, alongside other compounds like methionine and choline. The rate of DNA methylation is closely linked to the availability of these methyl donors{{pmid|28468239}}. TMG also acts to suppress various inflammatory expression profiles, including TNF-α, COX2, and NF-kB activity{{pmid|16282556}}. | [[Trimethylglycine (TMG)]], also known as betaine, was initially derived from the beetroot plant and is recognized for its osmoprotectant and anti-inflammatory properties. As a primary methyl group donor, TMG plays a significant role in DNA methylation processes, alongside other compounds like methionine and choline. The rate of DNA methylation is closely linked to the availability of these methyl donors{{pmid|28468239}}. TMG also acts to suppress various inflammatory expression profiles, including TNF-α, COX2, and NF-kB activity{{pmid|16282556}}. | ||
| Line 328: | Line 328: | ||
However, the specific effects of NMN or direct NAD+ conversion on methylation levels have yet to be thoroughly investigated. Therefore, concurrent supplementation of NMN, NAD+, or other NAD+ precursors along with TMG could be a strategic approach to prevent a decline in TMG levels. This co-supplementation may ensure the maintenance of proper methylation health and function, thereby supporting overall well-being and potentially mitigating age-related decline. | However, the specific effects of NMN or direct NAD+ conversion on methylation levels have yet to be thoroughly investigated. Therefore, concurrent supplementation of NMN, NAD+, or other NAD+ precursors along with TMG could be a strategic approach to prevent a decline in TMG levels. This co-supplementation may ensure the maintenance of proper methylation health and function, thereby supporting overall well-being and potentially mitigating age-related decline. | ||
=== Flavonoids: Quercetin, Fisetin, Luteolin/Luteolinidin, and Apigenin === | |||
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}}. | |||
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}}. | |||
'''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}}. | |||
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. | |||
==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: | ||