The article is a roundup of NMN research in the first half of 2022. With the continuous progress and development of science and technology, people’s health pursuit is becoming more intense. To ensure human health and improve the quality of life, the scientific community has conducted more and more research on anti-aging.
As a critical substance in the anti-aging field, NMN powder has been studied more and more in recent years, and its efficacy and safety have been continuously verified.
Half of 2022 has passed, and in this half year, there are a lot of research results on NMN; it is worth noting that 2022 research is no longer limited to foreign universities and institutions. Domestic relevant universities and well-known institutions constantly study NMN and NAD+ substances. Let’s have a look!
01 Chinese Academy of Sciences/Tsinghua University/Peking University: NMN may improve the symptoms caused by the virus.
On April 29, 2022, the Chinese Academy of Sciences, Peking University, and Tsinghua University published a blockbuster study in the international scientific journal Cell: The researchers found that COVID-19 infection caused genetic disorders in mice that were associated with NAD+ metabolism, immune response, and cell death, and NMN supplementation significantly improved the symptoms caused by these viral infections.
02 Tsinghua University: NMN improves liver protein acetyl group in aged mice.
A team led by Professor Deng Haiteng of Tsinghua University found that with aging, a variety of proteins in the liver, including those regulating fatty acid β-oxidation, tricarboxylic acid cycle, and valine degradation, as well as proteins such as NAD(P)+ hydrogenase (NNT) and cytochrome 3A25 (Cyp3a25), would undergo increased acetylation modifications.
The acetylation of these aging-related proteins was inhibited by NMN treatment.
This study suggests that NMN treatment can reprogram aging-related acetylation to reduce aging-related dysfunction.
03 Fudan University: NMN targeted prevention of ECHS1-deficient cardiomyopathy.
Short-chain enyl-CoA hydratase 1 (ECHS1) is a key enzyme in the oxidation of fatty acids and branched-chain amino acids, which is closely related to cardiomyopathy.
Researchers from the School of Life Sciences of Fudan University found that ECHS1 can regulate histone acetylation, so the etiology of ECHS1-associated cardiomyopathy may be the lack of ECHS1 leading to dysacetylation of histones in cardiac fibroblasts.
However, NMN can mediate histone acetylation and target prevent the development of ECHS1-deficient cardiomyopathy, which makes NMN supplementation a potential means of cardiomyopathy prevention. The article was published in Theranostics, a regional journal of Medicine.
04 Chinese University OF Hong Kong: NMN IMPROVES BLOOD vessels and helps fight atherosclerosis.
Atherosclerosis is a disease caused by atherosclerotic plaque deposition in the blood vessel wall, resulting in vascular stenosis. At first, there are no symptoms, but with the expansion of atherosclerotic plaque, patients will have coronary heart disease, stroke, and other serious consequences. It is triggered by vascular endothelial dysfunction and vascular inflammation in hyperlipidemia.
The Chinese University of Hong Kong biological medicine found that NAD + dependent on mitochondria, the lack of the acetylation enzyme SIRT3, causes vasodilation dysfunction, inflammation, mitochondrial respiratory damage, etc., promotes the development of atherosclerosis. The use of NAD + precursor treatment can reduce the intravascular plaque formation and improve blood vessel function and reduce vascular inflammation. The article was published in the authoritative journal of Antioxidants.
05 Tianjin Medical University: NMN can delay the aging of mesenchymal stem cells and may treat osteoporosis in the elderly.
In February 2022, a scientific study completed by a team from Tianjin Medical University was published in Aging Cell, a well-known journal in the field of Aging science. This study found that increased NAP1L2 protein level could lead to aging of mesenchymal stem cells, inhibition of bone osteogenic function, and trigger senile osteoporosis. Furthermore, through molecular screening, it was found that NMN could bind to NAP1L2 protein or be its specific inhibitor.
In subsequent animal experiments, administration of MSCS to aging mice could reduce the senescence level and improve osteogenic function. The team said that more studies would be conducted to verify the inhibitory effect of NMN on NAP1L2 and provide the theoretical basis for the treatment of age-related diseases.
06 Naval Medical University: Intravenous NMN can increase NAD+ levels in the brain and kidneys.
Professor Miao Chaoyu’s team from the Department of Pharmacology, Naval Medical University, injected 2g/kg NMN intravenously into normal mice and mice with ischemic stroke caused by middle cerebral artery occlusion and found that: After injection of NMN, the serum NMN content of mice increased sharply and then decreased rapidly within 15 minutes, while the level of NAD+ remained unchanged during 30 minutes of observation.
Over time, NMN and NAD+ accumulate in various tissues and organs, including the brain, especially in the kidney, which may be one of the reasons why NMN has the potential to be a “good medicine for kidney protection.”
In addition, 24 hours after NMN injection, the infarct size of ischemic stroke mice was smaller than before. In addition, high dose NMN did not induce acute toxicity in mice 14 days after injection.
This trial study demonstrates NMN’s potential for treating renal and cerebral diseases.
07 Chinese Academy of Sciences: NMN can alleviate the decline of intestinal structure and function during aging.
Under the Chinese Academy of Sciences, the Tianjin Institute of Industrial Biotechnology team found that NMN supplements had a protective effect on intestinal function in aged mice.
NMN supplementation has important effects on intestinal morphology, intestinal microbiota, inflammation, oxidation, antioxidant and barrier effects:
NMN administration for four months significantly increased the content of NAD+ in the jejunum of aging mice, improved the structure of jejunum, significantly increased villus length, and shortened crypts. In addition, NMN administration can alleviate inflammatory cytokine expression changes, reactive oxygen species production, and cell senescence induced to some extent.
08 The NAD+ precursor could become an important weapon in the fight against COVID-19 and other viral infections.
David Sinclair, a well-known scholar in the field of NMN, published a review article on NAD+ and novel coronavirus in Cell, pointing out that the concentration of NAD+ in tissues and organs of the elderly and patients with diabetes and cardiovascular diseases is reduced, which may lead to the fact that such people are more prone to severe coronavirus.
Multiple viral infections, including coronavirus, further deplete the NAD+ reserve in vivo, and many NAD+ -dependent enzymes, such as Sirtuins and the PARP family, have shown potent antiviral activity. Moreover, NAD+ also acts as an anti-inflammatory in mice and humans, avoiding the deadly cytokine storm of severe COVID-19.
Therefore, NAD+ precursors such as NMN can be used as emerging immunomodulators against infection and inflammation during viral infection and may become promising therapeutic targets for NEV.
09 NMN has a protective effect on glomerulosclerosis.
A team led by Kazuhiro Hasegawa of Tokushima University in Japan found that NMN protected mice from focal glomerulosclerosis induced by doxorubicin (ADR). The results found that:
①NMN alleviated urinary albumin excretion in doxorubicin mice;
②NMN treatment attenuated glomerulosclerosis and improved the expression of Sirt1 and claudin-1 in the kidney of mice.
③ The decrease of histone methylation and Dnmt1 expression in renal tissue were improved, and the concentration of NAD+ was increased.
These results suggest that short-term NMN treatment of focal glomerulosclerosis has epigenetic renal protective effects.
10 NMN significantly increased AMPK activity, a key factor in energy metabolism.
Japanese scientists Yamamoto, etc. treated human McF-7 breast cancer cells with 1mg/mL NMN, and NMN increased the intracellular NAD+ level by more than two times. Compared with untreated cells, the AMPK activity of cells treated with NMN increased by 1230.5% one hour after treatment and still increased by 849.2% 24 hours after treatment, indicating that NMN had a profound effect on enhancing AMPK activity, which may be the promotion of intracellular mitochondrial production and autophagy.
Experimental studies show that NMN can activate mitochondrial function and improve senescence.
11 NMN may improve the symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe and complex chronic rheumatic immune disease, with patients usually in a highly debilitating state.
Mona Dehhaghi and Gilles J. Guillemin of the University of New South Wales have found that impaired tryptophan metabolism, an important precursor of serotonin and NAD+, plays an important role in the pathophysiology of ME/CFS. Suggesting that NAD+ levels may be closely related to the disease.
Researchers have suggested that NAD+ precursor supplementation (e.g., NMN and NR) may improve ME/CFS symptoms and quality of life.
12 NMN can repair mitochondrial function and prevent diabetic peripheral neuropathy.
Axonal degeneration in diabetic peripheral neuropathy (DPN) is associated with impaired NAD+ metabolism.
The University of Maryland team tested NAD+ precursors NMN and NR to prevent DPN in type 1 and type 2 diabetes models. With two-month NMN or NR supplementation, the sensory function was improved, sciatic and caudal nerve conduction velocities were also normalized, and intraepidermal nerve fiber loss was reduced in hind paw skin samples in diabetic rats and mouse models.
The results showed that NMN supplementation could enhance the SIRT1/PGC-1α axis, thereby improving mitochondrial respiratory function, avoiding neuronal axonal degeneration associated with impaired NAD+ metabolism, and thus preventing DPN.
13 NMN is anti-allergy.
Researchers at Chonbuk National University, Korea’s oldest national flagship university, found that NAD+ precursor NMN inhibited mast cell degranulation in mice and humans, and intraperitoneal administration significantly attenuated mast cell-associated allergic reactions in mice. In the future, NMN may be a new treatment for allergic reactions.
14 NMN anti-melanogenic agent, targeting senile melanocytes.
Melanocytes produce melanin, which affects skin tone and hair color, and protects against ultraviolet rays. But aging can cause melanocytes to change, leading to pigmentation, such as age spots.
A research team at Ajou University in South Korea found that NMN, an anti-melanogenic agent, was ineffective in young melanocytes but significantly reduced melanin production in aged melanocytes by inhibiting cAMP/Wnt signaling, helping to improve aging-related pigmentation.
15 Taking NMN in the afternoon can improve the body mass and fatigue of the elderly.
On February 11, 2022, the results of a human clinical trial of NMN led by the University of Tsukuba in Japan were announced. This randomized, double-blind, controlled trial enrolled 108 subjects over 65 years of age and assigned them to receive 250mg NMN/ placebo before noon (after waking up to 12:00) and in the afternoon (from 18:00 to bedtime).
After 12 weeks of intervention, the subjects had no adverse effects; Participants in the afternoon NMN group performed better in lower limb function (as assessed by five sit-stand repetitions) and had significantly less fatigue (reduced sleepiness).
This study reaffirms the efficacy of NMN in improving fatigue and physical function, thereby improving the physical and mental health of the elderly.
16 There is evidence that oral NMN increases the level of NAD+ in the brain and reduces neurodegeneration.
A tight and complex structure between blood and brain cells is known as the blood-brain barrier. The existence of the blood-brain barrier can prevent most harmful substances from entering the brain and damaging the human body’s “headquarters.” But it also blocks access to most drugs, making it difficult to treat central nervous system diseases.
In animal studies, researchers at the University of Memphis found that oral NMN crossed the blood-brain barrier and increased NAD+ levels in brain tissue within 45 minutes.
This finding fills a big gap in the pharmacokinetics of NMN and provides a pharmacological theoretical basis for treating retinal degeneration, Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases by increasing the NAD+ level of NMN.
17 NMN supplementation rejuvenates aged oocytes.
Population aging has a significant adverse impact on female fertility and world population growth. The effect of aging on female fertility is mainly reflected in the reduction of oocyte quality. Young oocytes can be accurately identified and distinguished from senescent oocytes by non-invasive multispectral imaging.
Researchers from the University of South New Wales in Australia found that 85% of oocytes recovered the autofluorescence of young oocytes after feeding 12-month-old mice with NMN in water for 4 weeks, which was almost comparable to the young control mice aged 4-5 months, confirming the powerful effect of NMN against female reproductive aging.
18 The effect of NMN in promoting GLP-1 and lowering blood glucose is similar to that of “new hypoglycemic and weight loss drugs.”
GLP-1 (human glucagon-like peptide-1) receptor agonists, such as liraglutide and somarlutide, have become the most popular new drugs for diabetes treatment due to their strong hypoglycemic effect, low risk of hypoglycemia, good weight loss effect, clear cardiovascular benefits, and kidney protection. “Obesity” has also been approved for indications. Making GLP-1 receptor agonists a legitimate weight-loss drug.
GLP-1 is a gastrointestinal hormone secreted by intestinal epithelial cells, which promotes postprandial insulin secretion by islet β-cells to lower blood glucose. GLP-1 secretion is reduced in obese, glucose intolerant, and diabetic patients.
Researchers at Keio University in Japan found that feeding NMN to obese mice increased GLP-1 production, reduced postprandial blood glucose, and corrected obesity-related metabolic disorders. This study provides a novel molecular mechanism by which NMN is known to improve metabolism.
19 NMN ameliorates inflammatory bowel disease or may treat a variety of inflammatory diseases.
A study in Korea found that NMN supplementation reduced colitis severity and improved survival in mice. The researchers found that NAD+ deficiency in mice with inflammatory bowel disease (IBD), NAD+ deficiency often occurs in macrophages, leading to impaired phagocytosis. After the phagocytosis function of macrophages is impaired, it is difficult to kill pathogens effectively, so the inflammatory reaction is prolonged and aggravated.
This phenomenon is also seen in inflammatory diseases such as rheumatoid arthritis, diabetes, and sepsis. Therefore, increasing NAD+ levels in macrophages by oral NMN may help reduce the severity of various inflammatory diseases.
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