阅读说明：本技术 修复线粒体磨损、dna损伤，抗衰老的膳食配方 (Dietary formula for repairing mitochondrial wear and DNA damage and resisting aging ) 是由 蔚晨歌 于 2021-08-27 设计创作，主要内容包括：本发明提供了修复线粒体磨损、DNA损伤,抗衰老的膳食配方,属于药物配方技术领域,由以下重量份的原料制备而成：GoldenNAD+(烟酰胺β单核苷酸)30-400份,虾青素Astazine 10-300份。本发明的膳食配方,无毒副作用,具有修复线粒体磨损与DNA损伤,抗衰老的功效。(The invention provides a dietary formula for repairing mitochondrial abrasion and DNA damage and resisting aging, which belongs to the technical field of pharmaceutical formulas and is prepared from the following raw materials in parts by weight: 30-400 parts of GoldenNAD + (nicotinamide beta mononucleotide) and 10-300 parts of astaxanthin Astazine. The diet formula of the invention has no toxic or side effect, and has the effects of repairing mitochondrial abrasion and DNA damage and resisting aging.)

1. The dietary formula for repairing mitochondrial wear and DNA damage and resisting aging is characterized by being prepared from the following raw materials in parts by weight:

30-400 parts of GoldenNAD + (nicotinamide beta mononucleotide) and 10-300 parts of astaxanthin Astazine.

2. The dietary formula for repairing mitochondrial wear and DNA damage and resisting aging is characterized by being prepared from the following raw materials in parts by weight:

50-300 parts of GoldenNAD + (nicotinamide beta mononucleotide) and 20-200 parts of astaxanthin Astazine.

3. The dietary formula for repairing mitochondrial wear and DNA damage and resisting aging is characterized by being prepared from the following raw materials in parts by weight:

220 parts of GoldenNAD + (nicotinamide beta mononucleotide) 180-parts and 80-150 parts of astaxanthin Astazine.

Technical Field

The invention relates to the technical field of medicament formulas, in particular to a diet formula for repairing mitochondrial abrasion and DNA damage and resisting aging.

Background

At present, the existing anti-aging drugs have unobvious effects after being taken.

Disclosure of Invention

Aiming at the technical defects, the invention aims to provide a dietary formula for repairing mitochondrial abrasion and DNA damage and resisting aging, which has no toxic or side effect and has the effects of repairing mitochondrial abrasion and DNA damage and resisting aging.

In order to solve the technical problems, the invention adopts the following technical scheme:

the dietary formula for repairing mitochondrial wear and DNA damage and resisting aging is characterized by being prepared from the following raw materials in parts by weight:

30-400 parts of GoldenNAD + (nicotinamide beta mononucleotide) and 10-300 parts of astaxanthin Astazine.

Preferably, the feed additive is prepared from the following raw materials in parts by weight:

50-300 parts of GoldenNAD + (nicotinamide beta mononucleotide) and 20-200 parts of astaxanthin Astazine.

Preferably, the feed additive is prepared from the following raw materials in parts by weight:

220 parts of GoldenNAD + (nicotinamide beta mononucleotide) 180-parts and 80-150 parts of astaxanthin Astazine.

The invention has the beneficial effects that: the diet formula of the invention has no toxic or side effect, and has the effects of repairing mitochondrial abrasion and DNA damage and resisting aging.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The dietary formula for repairing mitochondrial wear and DNA damage and resisting aging is prepared from the following raw materials:

30-400 parts of GoldenNAD + (nicotinamide beta mononucleotide) and 10-300 parts of astaxanthin Astazine.

Preferably, the feed additive is prepared from the following raw materials in parts by weight:

50-300 parts of GoldenNAD + (nicotinamide beta mononucleotide) and 20-200 parts of astaxanthin Astazine.

Preferably, the feed additive is prepared from the following raw materials in parts by weight:

220 parts of GoldenNAD + (nicotinamide beta mononucleotide) 180-parts and 80-150 parts of astaxanthin Astazine.

Supplementary data

1. What is the NMN?

NMN is a fully known nicotinamid mononuleotide, nicotinamide mononucleotide, a naturally occurring bioactive nucleotide, and has 2 forms of irregular existence, α and β, NMN; the beta isomer is the active form of NMN and has a molecular weight of 334.221 g/mol.

Since niacinamide belongs to vitamin B3, NMN belongs to the category of vitamin B derivatives, and is widely involved in various biochemical reactions of human body, closely related to immunity and metabolism.

2. What are the sources of NMN?

NMN is widely distributed in daily food, vegetables such as cauliflower (0.25-1.12 mg NMN/100gm) and Chinese cabbage (0.0-0.90 mg NMN/100gm), fruits such as avocado (0.36-1.60 mg NMN/100gm), tomatoes (0.26-0.30 mg NMN/100gm), and meats such as raw beef (0.06-0.42 mg NMN/100gm) are rich in NMN.

NMN can also be synthesized via endogenous substances: 1 molecule of nicotinamide and 1 molecule of 5-phosphoribosyl-1-pyrophosphate (PRPP) produce 1 molecule of NMN and 1 molecule of pyrophosphate (PPi) under the catalysis of nicotinamide phosphoribosyltransferase (NAMPT or NAMPRT). The nicotinamide can be removed to form NMN, and 1 molecule Nicotinamide Riboside (NR) is phosphorylated to form 1 molecule NMN under the catalysis of Nicotinamide Riboside Kinase (NRK).

3. What role NMN has?

NMN is a precursor of NAD +, the function of which is also mainly represented by NAD +, and therefore NAD + is explained first:

NAD + is also called coenzyme I, and is known as nicotinamide adenine dinucleotide, which is widely distributed in all cells of a human body, participates in thousands of biocatalytic reactions, and is an essential coenzyme in the human body.

The specific reactions in which NAD + participates are mainly the following: growth, DNA repair (PARPs mediated), SIRTs protein, NADP (H) synthesis.

(ii) NADP (H) pathway:

the metabolism of NADP (H) is delayed compared to NAD (H), which does not mean a slower conversion rate of NADP (H), but means that NADP (H) is the downstream reaction of NAD (H), because of the very stable "time difference" between the two reactions.

The size of the NADP (H) pool is only 1/20 of the NAD (H) pool, the proportion of NAD + consumed by NAD kinase, normally around 10% of total NAD +, 12 pmol/million cells/hour, while the total consumption of NAD + is about 118 pmol/million cells/hour.

② PARPs pathway:

under normal conditions PARPs consume approximately 1/3 NAD +, and when DNA damage requires repair, consumption of PARPs will dominate even more.

③ the SIRTs pathway:

SIRTs consumed approximately 1/3 NAD +, about 32 pmol/million cells/hour under normal conditions, in a ratio similar to PARPs.

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With age, NMN and NAD + levels decline on average, while NAD + metabolite NAM rises.

The decline of NAD + during aging is considered to be a major cause of diseases and disabilities such as hearing and vision loss, cognitive and motor dysfunction, immune deficiency, arthritis due to dysregulation of autoimmune inflammatory responses, metabolic disorders and cardiovascular diseases.

Therefore, NMN supplementation increases NAD + levels in vivo, thereby delaying, ameliorating, and preventing aging-related phenotypes, or age-induced metabolic disorders, geriatric diseases, and the like. The function is as follows:

A. NAD + and circadian rhythms

The NAD + -dependent deacetylase SIRT1 bridges the circadian rhythm and metabolism by linking an enzymatic feedback loop that regulates the NAD + -salvage pathway and a circadian transcription-translation feedback loop.

NAD + regulated biological clocks were achieved by SIRT 1. SIRT1 deacetylates BMAL1 and PER2, which is antagonistic to the acetylation function of CLOCK, so SIRT1 inhibits CLOCK-BMAL 1-mediated transcription of CLOCK genes. Thus, NAD + affects SIRT1 deacetylation activity by itself levels, which in turn affects the expression of a range of biological clock-related proteins including NAMPT.

Biological clock regulation is associated with many diseases including, but not limited to, sleep disorders, diabetes, tumors. Many pathological processes are triggered by disorders of the biological clock, which may be genetic or environmental, and in all, maintaining the biological clock in normal operation plays an important role in maintaining health.

B. NAD + and the nervous system

Sirtuins are nicotinamide adenine dinucleotide (NAD +) dependent deacylases that have traditionally been implicated in caloric restriction and senescence in mammals. These proteins also play an important role in maintaining neuronal health during aging.

During the neural development process, SIRT1 plays an important role in structure, and promotes axonal growth, neurite growth and dendritic branching through an Akt-GSK3 pathway. The development of synapses and the regulation of synaptic strength are crucial for the formation of memory, while sirtuins proteins play an important regulatory role in this process, both physiologically and after injury. SIRT1 may exist in the hippocampus as a repressive complex comprising the transcription factor YY1 that regulates microRNA-134. The distribution of the microRNA-134 has brain specificity, and can regulate the expression of cAMP response binding protein (CREB) and brain-derived neurotrophic factor (BDNF). This is important for both synapse formation and long-term enhancement.

During the development of neurological diseases, SIRT1 plays a protective role in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and motor neuron disease, and the diseases are probably related to the functions of SIRT1 in metabolism, stress resistance and genome stability. Drugs that activate SIRT1 may provide promising approaches for treating these diseases.

C. NAD + and cancer

Studies with increased NAD + levels in the treatment of cancer have shown that: firstly, the overexpression of the NMNAT3 improves the mitochondrial NAD + level and inhibits the growth of glioblastoma cells; ② supplement of NA or NAM can inhibit tumor growth and multi-organ tumor metastasis of SCID mice.

The principle is as follows: excess NAD + promotes mitochondrial respiration, reduces glycolysis, and counteracts the Warburg metabolism preferred by cancer cells (cancer cell energy metabolism properties that are more dependent on glycolysis than oxidative phosphorylation); increasing NAD + also increases the activity of SIRT1 and SIRT6, both of which inhibit tumors by down-regulating β -catenin signaling, down-regulating glycolysis.

However, there are contradictions and concerns among them: NAD + promotes DNA repair and angiogenesis, potentially aiding cancer cell growth (existing long-term studies in wild-type mice fail to provide any evidence of tumor promotion). While decreasing tumor NAD + levels, cancer cells/tissues will become more sensitive to chemotherapeutic drugs as the ability of PARPs to repair DNA damage decreases. It would be very important to further test the effect of NAD + dietary supplements in standard cancer models.

D. NAD + and liver function

Enzymes in the NAD + signaling pathway are known to protect the liver from fat accumulation, fibrosis and insulin resistance, all of which are associated with the development of fatty liver disease.

NAMPT plays a key role in the process of inducing the generation and development of fatty liver by high-fat diet: inhibition of NAMPT will make hepatic steatosis caused by high fat diet more severe, overexpression of NAMPT significantly improves hepatic lipid accumulation; this modulation is produced by "inhibiting NAMPT → reducing NAD + → inhibiting SIRT1 → attenuating deacetylation of SREBP1 → reduction of SREBP1 activity → up-regulation of FASN and ACC expression".

SIRT1 and its downstream targets PGC-1a, PSK9 and SREBP1 maintain mitochondrial function, cholesterol transport and fatty acid homeostasis. SIRT2 controls gluconeogenesis by deacetylating phosphoenolpyruvate carboxykinase; SIRT3 regulates OXPHOS, fatty acid oxidation, ketone production, and antioxidant stress; SIRT6 controls gluconeogenesis.

Due to the importance of these pathways in the liver, maintaining NAD + levels is essential for maintaining good organ function. Normally, due to obesity and aging, NAMPT levels fall and CD38 levels rise, resulting in a 2-fold decrease in steady-state NAD + levels by middle age.

Increasing NAD + levels to young levels has significant effects in preventing and treating obesity, alcoholic steatohepatitis and NASH, while also improving glucose homeostasis and mitochondrial dysfunction, improving liver health, enhancing its regenerative capacity, and protecting the liver from hepatotoxic damage.

E. NAD + and renal function

The reduction in NAD + levels and the corresponding reduction in sirtuin activity in the elderly kidney is largely responsible for the decline in renal function and compliance with age.

Activation of SIRT1 and SIRT3 by NAD + supplementation protects against high sugar-induced mesangial cell hypertrophy, while treatment of mice with NMN protects against cisplatin-induced Acute Kidney Injury (AKI) in a SIRT 1-dependent manner.

② 5-aminoimidazole-4-carboxamido nucleosides stimulate AMPK activity, increase NAD + levels, and protect cisplatin-induced AKI in a sirt 3-dependent manner.

Supplying NAM to the mouse can stimulate the secretion of kidney protection prostaglandin PGE2 and improve the kidney function after ischemia; NAM can also inhibit cisplatin-induced AKI by stimulating NAD + synthesis.

F. NAD + and skeletal muscle

The muscle wasting and inflammation markers as well as the insulin signaling and insulin-stimulated glucose uptake capacity of the mice are reduced compared to young wild-type mice. Treatment of older mice with NAD + precursors can significantly improve muscle function.

Treatment of aged mice with NMN (500mg/kg/day ip. for 7 consecutive days) reversed the age-related detrimental changes by increasing mitochondrial function, increasing ATP production, reducing inflammation, and converting glycolytic type II muscle to oxidized fiber muscle.

G. NAD + and cardiac function

NAD + levels are critical for normal cardiac function and recovery after injury. Of all NAD + -dependent signaling proteins, SIRT3 appears to be the most important:

SIRT3 knock-out mice are hyperacetylated by OXPHOS enzymes, reduced ATP, and highly sensitive to aortic contraction, probably due to activation of the regulatory factor CypD of the mitochondrial permeability transition pore.

② SIRT3-KO mice will develop fibrosis and myocardial hypertrophy at 13 months of age, with the condition further aggravating with age, and NMN treatment can reverse this decline.

③ No matter 30 minutes before ischemia (500mg/kg, i.p.) or repeated administration before and during reperfusion, the treatment with NAMPT over-expression or NMN can significantly prevent pressure overload and ischemia-reperfusion injury, and reduce the infarct size by about 44%.

And fourthly, the heart function of the aged MDX cardiomyopathy mouse is also improved by using NAD + precursor for treatment.

NAD + precursor improves the mitochondria and heart function of the heart failure mouse model induced by iron deficiency.

Sixthly, NAD + precursors can protect and restore cardiac function to essentially normal levels even in a friedrich's ataxia (FRDA) cardiomyopathy mouse model by activating SIRT 3.

H. NAD + and vascular endothelial cells

Endothelial Cell (EC) senescence is a pathophysiological process with structural and functional alterations including deregulation of vascular tone, increased endothelial permeability, arteriosclerosis, impaired angiogenesis and vascular repair, decreased EC mitochondrial biogenesis, etc.

Cell cycle disorders, oxidative stress, calcium signaling changes, hyperuricemia, and vascular inflammation are closely related to the occurrence, development, and progression of EC aging and vascular disease. Many aberrant molecular pathways have been implicated in these underlying pathophysiological changes, including activation of SIRT1, Klotho, fibroblast growth factor-21, and the renin angiotensin-aldosterone system.

Because of the relationship between SIRTs and vascular aging, the recruitment of NAD + precursor NMN has been shown to be effective in several studies:

NMN treatment of old mice (administered 300mg/kg daily for 8 weeks) can restore carotid artery endothelium-dependent dilatation (endothelial function measurement), while reducing aortic pulse wave velocity and elastic arterial stiffness.

② NMN (500mg/kg/day, water administration, continuous 28 days) has significant efficacy for the treatment of mice: by promoting sirt 1-dependent increases in capillary density, blood flow and endurance were improved in older mice.

And thirdly, NMN remarkably improves cognition of the aged mice by improving age-induced vascular endothelial dysfunction and neurovascular coupling (NVC) reaction of the aged mice, reduces the mitochondrial ROS of brain microvascular endothelial cells of the aged mice, and recovers NAD + and mitochondrial energy.

Increasing NAD + levels in the vascular endothelium would potentially be a potential therapy to increase mobility in the elderly and to treat diseases that develop due to reduced blood flow such as: ischemia-reperfusion injury, slow wound healing, liver dysfunction, muscle myopathy, and the like.

I. NAD + and metabolic disorders

NMN has effects of improving obesity, type II diabetes, and reproduction inhibition caused by fat metabolism and glucose metabolism disorder, and can even improve adverse effect of obese mothers on female offspring reproduction.

4. What way is there NAD + replenished?

NAD + has so many effects, how should we replenish it? Why did NMN be selected?

The main routes for the synthesis of NAD + are still introduced first:

the synthesis of NAD + is divided into salvage pathway, de novo synthesis pathway and Preiss-handler pathway according to different synthetic raw materials.

a) De novo synthetic route: tryptophan (Trp) is converted to Quinolinic Acid (QA) and then converted to NAMN by quinolinic acid-phosphoribosyltransferase (QPRT). NAMN is converted to NAAD and ultimately NAD + is catalytically generated via NAD + Synthetase (NADs).

b) The P-H synthetic pathway (also called NA salvage pathway): niacin (NA) synthesizes NAD + via NAPRT, NMNAT, NADS (NAD synthetase).

c) Salvage synthesis pathways (also called NR salvage pathways): nicotinamide Riboside (NR) or Nicotinamide (NAM) is synthesized into Nicotinamide Mononucleotide (NMN) by NRK (nicotinamide riboside kinase) or NAMPT and NMNAT, and NMN is synthesized into NAD + by NMNAT1-3 enzyme.

Nicotinic acid Nucleoside (NAR) also produces NAMN catalyzed by NRK, followed by enzymatic synthesis of NAD + via 1.

NAD (H) concentration of various organs and tissues of mammals

The preference of mammalian tissue organs for NAD + starting materials is primarily related to the tissue specificity of the NAD synthetases they express.

The liver uses tryptophan to synthesize NAD + de novo, secreting large amounts of NAM (nicotinamide) during the synthesis-use NAD + cycle, which can be taken up and utilized by other organ tissues with the cycle.

Endogenous Nicotinic Acid (NA) is rarely slowly interchanged in blood-tissue organs, most of which do not rely on NA in blood for NAD synthesis.

Other tissues than liver rely more on circulatory transported NAM to synthesize NAD. Skeletal muscle is the tissue that is least efficient in the uptake of NAM to synthesize NAD +, and the small intestine and spleen are the tissues that are most efficient in the synthesis of NAD + using NAM.

5. Which organs like NMN and which do not?

The synthase, consuming enzyme of NMN is also tissue specific:

NMN is widely distributed in tissues and organs throughout the body, and is present in various cells from the embryonic development stage.

The metabolism and biodistribution of NAD + precursors in various tissues and cells is poorly understood, in contrast to the expression of the NMN-consuming enzymes NAMPT and NRKs, which are the most well understood enzymes NMN.

(1)NAMPT

NAMPT is ubiquitous in vivo, but there are large differences in expression levels between tissues. In brain and heart, NAMPT-dependent salvage pathways are the first mode of NAD + production; while in skeletal muscle, the NRK-dependent salvage pathway is the first mode of NAD + production.

(2) NMNATs (NMN consuming enzymes)

The mouse tissue metabolism spectrum shows that the activity of the NMNAT subtype is far higher than that of NAMPT, and the activity of the NMNAT subtype is not limited in most tissues except blood.

(3)NRKs

Expression analysis of the NRK subtype showed that NRK1 is ubiquitous, whereas NRK2 is mainly present in skeletal muscle. Consistent with this, chronic NR supplementation causes increased NAD + levels in muscle, but has little effect on brain or white adipose tissue.

Promotion of NAD + by oral NMN:

although the full structure of NMN could not be detected in serum, oral NMN still rapidly (15min) increased NAD + levels in female, male mice;

6. how does NMN enter cells?

NMN has membrane transporters on some cell surfaces, which can directly transfer NMN into cells, so NMN has two ways to enter cells:

directly entering cells through transporters: in the beginning of 2019, a paper of nature metablism confirms the idea, and the paper finds that an NMN specific transporter exists in the small intestine of a mouse, is called Slc12a8, is an amino acid and polyamine transporter, has high selectivity on NMN, and does not transport and has a structure which is very similar to NaMN.

② the cell enters the cell through dephosphorylation of CD73 on the surface of the cell membrane into NR (through balancing nucleoside transporter ENTs), then enters the mitochondria to be utilized (the mitochondria has no NRK) through catalysis of NMN by the NRK enzyme of the cytoplasm.

NAM is both a precursor of NMN and a product of the hydrolysis of NAD + via the NADase activity consuming pathway CD 38. Thus, the synthesis, utilization and regeneration of NAD + is a cycle involving intracellular and extracellular NMN/NR → NAD + → NAM → NMN.

Astaxanthin, a powerful natural antioxidant, is a novel nutritional super giant star. Astaxanthin is also a food pigment that turns shrimps and salmon red. This surprising nutritional dietary supplement, which is described by experts as belonging to the carotenoid family, is several thousand times more powerful than vitamin C in scavenging free radicals and plays a key role in preventing degenerative aging diseases.

The research shows that the astaxanthin has the following effects

Preventing and treating dementia

A study published in the British Journal of Nutrition found that astaxanthin reduces 50% of the harmful free radicals in blood. Doctor kola said: we have found an abnormal accumulation of hydroperoxides in the red blood cells of the population suffering from dementia and Alzheimer's disease. We now know that if you take astaxanthin to these patients, the accumulation of harmful free radical hydroperoxides decreases by 50%. This reduction is quite significant ".

Relieving arthritis pain

Reports indicate that: when arthritis patients take 4 mg of astaxanthin per day, their joint pain was reduced by 85% and their mobility was improved by 60%. Most people consider astaxanthin dietary supplements to be as effective as prescription drugs.

Reducing cholesterol

The hypercholesterolemic patients were administered astaxanthin at a dose of 6, 12, or 18 mg per day, respectively. At the end of week 12, astaxanthin significantly reduced (bad) cholesterol levels and increased HDL (good) cholesterol levels, although total cholesterol levels remained unchanged. This study, published in the journal Atherosclerosis, has found that the (good) cholesterol increase is greatest in people taking 6 mg and 12mg daily.

Preventing diabetes

A study published in Journal of Agricultural and Food Chemistry found that astaxanthin protects cells from damage due to excessive blood glucose levels, reduces kidney disease, reduces neuropathy, and reduces diabetic retinopathy.

Preventing heart disease

A report published in journal of Future Heart disease (Future Cardiology) analyzed 8 clinical trials and as a result, astaxanthin was found to be antioxidant against oxidative stress and to have anti-inflammatory properties. Oxidative stress and inflammation are also two important factors in the development of heart disease. A study published in Nutrition and Metabolism (Nutrition and Metabolism) found that astaxanthin reduces the levels of C-reactive protein in inflammation producers.

Other studies have shown that astaxanthin smoothes wrinkles, secures the eyes, increases endurance and strength, burns fat, and improves fertility in men.

It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.