EN 
CN Longevity Science
The human body is a wonderful and complex structure, containing various organs, sharing different roles, complementing each other, coordinating and balancing each other, and maintaining various body functions at all times. However, each human body is derived from an embryonic cell (fertilized egg) containing 23 pairs of chromosomes, half from the father and half from the mother.
It is from this fertilized egg that various cells are developed, different tissues are formed, and various organs of the body are constructed. Among the nearly 30 trillion cells in the human body, they all contain the same genetic sequence.
The human body is like a machine, there will always be a day of decay. Dating back to ancient times, people who lived to the age of fifty were considered long-living. There is a saying that “life is rare at seventy years old”, and there are very few people who can live till their seventies.
With the improvement of social conditions and the advancement of medical technology, human life expectancy continues to increase. Data released by the Census and Statistics Department in 2021 shows that the average life expectancy of men and women in Hong Kong has increased significantly by more than 8 years compared with 1986. The average life expectancy of men is now 82.9 years and that of women is 88 years.
However, we are not only concerned with “lifespan”, but whether we can have the quality of life like we are young when we get old — “healthspan”.
What is aging?
The most obvious signs of human aging are wrinkles on the face, neck and back of the arms and hands. The skin is no longer moist and shiny, and even the skin is dehydrated due to poor blood circulation and decreased sebum secretion. The elderly will gradually experience a decrease in muscle mass, a state of reduced muscle strength and motor function at the same time, and poor balance and body flexibility.
The internal organs of the body degenerate, physical energy declines, the gums shrink, and the digestive function is weakened. The five senses (vision, hearing, touch, smell, and taste) will also gradually decline significantly, and memory and thinking abilities will slowly decline.
Causes of aging
Aging has always been regarded as an irreversible natural process. The functions of the body wear out over time, the body organs gradually degenerate, the mobility decreases, the risk of disease increases, and in the end, life ends in death.
The human body is composed of cells. From a cellular aspect, how does aging occur?
1. DNA Damage: UV, XR, Free Radicals
The backbone of a cell’s life structure is its genetic material. The DNA sequence is transcribed into RNA and then used to synthesize various proteins required for life to maintain normal cellular functions.
However, in daily life, genomic DNA will continue to experience continuous challenges and attacks; including attacks from the outside, such as ultraviolet rays, X-rays, radiation, oxidants, alkylating agents or other toxic organic compounds, as well as some toxic substances from inside the cell. Damage caused by metabolites such as reactive oxygen species (ROS) and free radicals.
Over the years, through these internal and external challenges and adversities, various complex biochemical systems and functions in cells will begin to degenerate.
2. Decreased autophagy (senescence cells)
Under normal circumstances, the metabolites and damaged parts inside the cell will slowly accumulate, and then they will be removed through a self-digesting mechanism, which is biologically called autophagy.
Autophagy in cells declines with age, and when damaged tissue and waste build up, cleaning becomes difficult, causing proteins to accumulate in aging cells and causing problems with DNA replication.
When a cell can no longer manage the accumulation of waste products within its cell membrane, it interferes with normal division and loses its original function. During this period, the cell neither dies nor reproduces properly or performs its function efficiently, but keeps producing destructive molecules like zombies that interfere with or even harm nearby healthy cells. When these senescence cells continue to accumulate in the body and the immune system fails to clear them in time, various aging-related phenomena and diseases will start to surface.
3. Deviation in Epigenome
The human body is made up of up to 200 different types of cells – epithelial cells in the skin, cardiomyocytes in the heart, neuronal cells in the neural network, etc. They have very different shapes and functions, so it’s not difficult to tell the difference between cardiomyocytes and neurons. Have you ever wondered why there are so many differences in appearance and function even though all cells in everyone have the same DNA?
Apparently, genes in different cells are selectively expressed and perform different roles and functions. However, how do cells know their identity?
Each human body is developed from the replication and division of an embryonic cell, and the nucleus of each cell inherits the same genetic chromosomes. The main component of chromosomes is DNA (deoxyribonucleic acid, deoxyribonucleic acid) double helix structure, each DNA molecule contains a base part (nitrogenous base, or nitrogen base), respectively cytosine (cytosine, C), Thymine (thymine, T), adenine (adenine, A) and guanine (guanine, G). The ACTG base sequence on the chromosome is the genetic code of the gene sequence. Human cells contain about 25,000 genes, and each cell contains the same genome.
Scientists have found that there is actually an epigenome on top of the cell genome, which determines and regulates the expression of genes. When a cell divides, the epigenome instructs the post-dividing cell which genes need to be expressed and which do not need to be expressed, and to what extent, without modifying the DNA gene sequence. In other words, cells with the same genes develop into different tissues and organs under epigenetic control.
With the development of science and technology, scientists have a detailed understanding of how the epigenetic mechanism works. The DNA gene sequences of chromosomes in the nucleus interact with many smaller molecules in the cell, and epigenetic mechanisms can interfere with (promote or repress) the transcription of specific genes. There are two common ways of interfering. One is to put chemical labels on specific positions on the DNA gene sequence. For example, methyl groups can inhibit the expression of genes. As a result, the genes are still there, but remain silent. On the contrary, acetyl groups can promote the expression of genes and accelerate the expression of genes. Associated with mRNA transcription and protein manufacture. Another way to interfere is through the DNA double helix wrapped around histones to suppress gene expression.
In this way, the body divides and grows from the starting genome of embryonic cells, and the epigenome determines which genes are activated and which are inhibited, and then develop into heart cells, liver cells, muscle cells, and the different tissues and organs of the body. Genetic medicine studies have confirmed that the epigenome is affected by environmental factors, changing the chemical tags on the DNA gene sequence. These factors include diet, exposure to chemicals and drugs, and more. For example, chemical tags that stop making genes that suppress tumor proteins can trigger cancer.
Analysis of the chemical tags on the DNA sequence of the epigenetic machinery also found that as the body ages and cells continue to grow and divide, the number and location of these chemical tags changes significantly, which is very different from the epigenome of young cells , the expressed genes are silenced, and the genes that should not be expressed become active, the cells slowly begin to deviate from their original roles, the original skin tissue cells begin to slow down the division speed, and the divided cells may have lost their original performance, or even Mutations, unable to repair the damage of the environment normally, increase the risk of disease, and lead to death step by step. This phenomenon is called “epigenetic disorder” in biology.
4. Malfunctioning DNA and cell repair systems
Survival and reproduction are the basic needs of living beings. Body cells will be damaged continuously. To survive, they need to be repaired. Repair work is not limited to repairing DNA, but also organelles and cell membranes. When the related proteins start repairing at the DNA break, several proteins can get stuck on each other if the DNA replicase, which is responsible for cell division, comes to the break at the same time. In most cases, reproductive work is prioritized, and the repair process is forced to be interrupted. As a result, the genes of the two divided cells cannot be expressed normally or even die.
Therefore, the cellular gene program has a built-in coordination mechanism, and the repair protein responsible for repairing DNA binds to the gene that inhibits division and reproduction when no damage occurs, and gets stuck on this gene to prevent transcription and prevent it from being expressed. When DNA damage occurs somewhere, this protein, in a chain reaction, breaks away from the inhibiting reproduction gene suppressed by it to repair the DNA. At this time, the inhibiting reproduction gene begins to express, and the corresponding protein is produced to hinder the replication of DNA, suspend reproduction and support maintenance. The program, when the repair protein completes the repair work, comes back and suppresses the reproduction-suppressing gene so that it is no longer expressed, and healthy cells can reproduce again. This is a complete life circuit.
However, this mechanism is not completely reliable. Repair proteins that run out to repair DNA may get lost in the intricate cell maze. After more and more cell aging damage, they have been busy repairing proteins to complete the repair work, failing to return to the previous one. A position that should play an inhibitory role in normal times. There are more and more situations where the maintenance and replication of DNA gene sequences cannot be coordinated, and the silenced gene will always be expressed, the expressed gene will continue to be silenced, and the cells will not be able to perform their own functions normally. For example, stem cells cannot divide various cells. Body organs begin to age.
The role of genes/anti-aging genes
In daily life, we should try to avoid damage to DNA genetic material, reduce exposure to ultraviolet, X-ray or other radiation, and avoid exposure to toxic organic compounds or other chemical substances.
Pay attention to your daily diet, try to eat natural foods, as well as fruits and vegetables that contain antioxidants. Refined foods generally contain a lot of chemicals, which can put weight-seeking pressure on the body’s digestive system, circulatory system, immune system, and even cells, accelerating the aging process.
Anti-aging gene
The self-healing ability inside the cell is controlled by genes and epigenetics. The repair mechanism works at full capacity during adolescence. After the age of childbearing and raising offspring, that is, after about 40 years old, the repair proteins in the body begin to decrease or fail, as mentioned above. Repair proteins, which have both functions of repairing cells and inhibiting gene replication, get lost because of too many repair tasks, and genes and intracellular tissue damage cause genes to be expressed indiscriminately.
Cells start to let the environment damage them and stop trying to repair them, and we start to age and become weaker until various diseases take us away. However, as we age, the genetic information contained in the genes in each of our cells does not change. The genes that control repair proteins have always been there, but it seems to be turned off or shrunk because of changes in the epigenome. Now, is there a way to activate it again?
In the past 30 years, scientific research has found that there are three sets of genes in the human body that affect the aging process and lifespan. By controlling these three sets of genes, the aging process can be changed or even reversed. Life genes can be divided into three groups: mTOR, AMPK, SIR.
mTOR
mTOR (m: Mammal; TOR: Target of Rampamycin) can sense protein and amino acid levels in the body and regulate cell growth. When protein levels rise, such as after eating a large steak, the mTOR gene is turned on and becomes active, promoting protein synthesis to supply energy for cell division and growth.
In 2013, Dr. Matt Kaeberlein gave a 20-month-old mouse (equivalent to a 75-year-old human) rapamycin to inhibit mTOR in the mouse by 25%, and the average lifespan of the mouse was prolonged. about 20%. In 2021, he gave middle-aged dogs a low dose of rapamycin and found that their hearts functioned stronger and younger than before, and research will continue to follow their longevity.
When the body lacks sufficient nutrients, the mTOR mechanism is inhibited, slowing down protein synthesis to conserve energy, while removing damaged cells and waste through autophagy, reusing nutrients. However, we cannot prolong life by inhibiting mTOR alone, because insufficient amino acids and protein can have a series of side effects, such as weakened immunity, problems with bones, muscles and fertility. A balance must be struck between reducing protein inhibition of the mTOR mechanism and maintaining a healthy state of the body.
AMPK
AMPK is present in the cells of most living things. Its main function is to monitor the energy status of the cells. Once it detects that the calories we absorb are lower than the level we need, it will start, stop cell growth, and start to burn the body. fat to maintain our energy supply. The activation of the AMPK gene makes cells more sensitive to insulin response, promotes the absorption of glucose in the blood by cells, enhances mitochondrial (mitochondria) function, and allows cells to have a more stable energy supply. Studies have confirmed that relatively low blood sugar levels are actually good for our bodies, reducing the risk of cancer, heart disease, cardiovascular disease, and extending life.
AMPK has a balancing effect on mTOR. When AMPK is activated, mTOR will be inhibited at the same time. As mentioned above, the body will initiate autophagy to actively remove damaged cells and metabolic waste. The study found that long-term use of a drug that activates AMPK in mice increased lifespan by about 15 percent.
Reducing calorie intake can activate the AMPK mechanism, but it is very difficult for us to restrict our diet for a long time. Long-term hunger can trigger mood swings, lowered metabolic rate and weakened immunity, making people prone to fatigue and illness. Considering the lifestyle of urbanites, it is difficult to strictly limit calorie intake or exercise a lot.
SIR
SIR – Sirtuins gene, can be regarded as one of the most primitive biological genes, and it has been traced from single-celled organisms. There are seven sets of SIR genes in human body cells, which produce seven corresponding proteins, which are distributed in the nucleus, cytoplasm and mitochondria, and play a very critical role in the repair and maintenance of DNA and other components in the cell.
The SIR protein is a repair protein that acts as an “OFF” regulator by attaching to genes that inhibit cellular DNA replication and cell division. What is clear here is that the SIR protein binds to a gene that inhibits division and reproduction, and gets stuck on this gene to prevent transcription from happening, which is equivalent to holding it down and not letting it express. In other words, it is to allow cells and DNA to replicate and divide and enter the growth and reproduction machinery. When the DNA is damaged somewhere, this protein will break away from the inhibiting gene that is suppressed by it in a chain reaction to repair the DNA at the position of the break. At this time, the inhibiting gene will begin to express, and the corresponding protein will be produced to hinder the DNA. Copying doesn’t make it multiply. During this time, the work of dividing and duplicating DNA is halted for repairs. When the repair work is completed, the SIR protein is re-engaged on the gene just now, allowing the cell to re-enter the growth and reproduction mechanism.
There are two main operating mechanisms inside the cell, one is repair and protection mode, and the other is growth and reproduction mode. The SIR protein puts the cell into repair protection mode so that damage can be repaired, the cell returns to its normal state, and the cell enters growth and reproduction mode. There are about 30 trillion cells in each human body, and there are as many as millions of damaged DNA and cell components that need to be repaired every day. Facing the huge repair demand, the SIR protein gene needs to produce a large amount of SIR protein, and it also needs to have enough energy and raw materials to work, the burden is very heavy.
On the other hand, when the body faces adversity, such as a hot or cold environment, starvation or physical injury, and other situations that threaten survival and safety, the SIR gene also becomes active, putting the body into repair maintenance mode. SIR genes also play key roles in many functions that regulate the aging process, including regulation of intracellular mitochondrial production (mitochondrial biogenesis), regulation of programmed apoptosis (apoptosis) and autophagy for the recycling of cellular materials Utilize and stimulate the signal transduction between the nucleus and mitochondria, inhibit inflammation, etc., so the SIR gene is often referred to as the “longevity gene”.
Practice healthy longevity
- To prevent DNA damage, use sunscreen products to combat UV damage, reduce exposure to X-rays or other radioactive substances, and avoid exposure to toxic chemicals, smoking, or drugs.
- Appropriately reducing food intake, studies have pointed out that proper restriction of calorie and protein intake can activate anti-aging genes, put the body into a protective repair mode, make good use of body resources, and remove metabolic waste or aging cells.
- Do more high-intensity physical exercise to promote blood circulation in the body, stimulate the immune system, activate the SIR gene, and make the body more focused on repair and maintenance work.
- On the whole, it is to keep the body in a repair and maintenance mode to keep cells, tissues, and organs in overall health.
Anti-aging supplements
Resveratrol
“Resveratrol” is a plant polyphenol compound with antioxidant, anti-aging and anti-inflammatory effects. It is commonly found in grape skins, peanuts, and cocoa. Taking grapes as an example, growing in an environment with extremely abundant sunlight, plants are constantly subjected to external stress or shock, such as extreme ultraviolet rays, insufficient environmental nutrients, and attack by mold or bacteria. To combat external adversity, plants produce resveratrol to protect their cells and grow. Resveratrol in plants is generally divided into two forms: trans (trans-) and cis (cis-), among which trans-veratrol is more stable and has significantly better efficacy in animals, so it has become the current supplement the main ingredient.
In addition to its antioxidant and anti-inflammatory properties, recent large studies have found that resveratrol plays a key role in extending healthy lifespan. Combining 19 clinical studies on different species, scientists found that it can activate sirtuins, promote the ability of autophagy, and remove wastes in cells, so as to slow down the degradation of body functions and prolong life.
As mentioned above, one of the biggest problems of aging is that it is accompanied by various functional declines, and different studies have found that resveratrol can reduce our risk of cardiovascular disease, neurological decline and other physiological diseases. Dementia (also known as Alzheimer’s disease) is a growing global concern.
Even though the cause is still unknown, the problem of brain degeneration is believed to be related to neuroinflammation and the formation of Beta Amyloid (aβ) plaques in the brain. In order to study the efficacy of resveratrol against aging-related diseases, in 2017 the Georgetown University School of Medicine in the United States randomly divided 119 patients with Alzheimer’s disease into two groups, one group took resveratrol, while the other group received No. After 52 weeks, using magnetic resonance imaging, the researchers found that the resveratrol-treated group was stable on various neuro-biomarker tests, with improvements in Aβ accumulation and brain inflammation, while the other group experienced persistent deterioration. It can be seen that resveratrol can help protect brain nerve cells and help delay aging-related degenerative diseases.
NMN
The Sirtuin “longevity gene” has diverse functions, ranging from regulating cell metabolism to repairing DNA, and plays a key role in anti-aging. The Sirtuin protease produced by the SIR gene’s instructions requires the use of NAD as an energy source. NAD, a derivative of vitamin B3, is involved in many body operations and plays a particularly important role in metabolism, DNA repair, and gene expression. NAD levels in the body peak at the age of 25, but as we age, NAD levels gradually decline and the function of the Sirtuin protein diminishes. Due to the decline of DNA repair function, although cells can continue to replicate themselves, more and more cells are damaged by replication and division, while the number of healthy cells is decreasing. In the case of ebb and flow, bodily functions will begin to malfunction, that is, aging. To use an analogy, if Sirtuins are employees of a company, then NAD is the money that pays employee salaries, office rent and expenses, etc. without which the company cannot function.
Fortunately, we can directly increase NAD levels in the body through supplements. In 2013, Dr David Sinclair found that older mice had relatively lower levels of NAD than younger mice. In the experiment, he added NMN to the drinking water of aged mice, and after just one week, he found that the number and density of their microfilament blood vessels returned to the level of young mice, and there was no obvious difference in the sample tissues of the two mice. respectively. The muscle blood flow of the aged mice also increased significantly, and even more strikingly, their physical fitness increased by 60% to 80%, and they could run 1400 feet continuously on the treadmill; compared with the mice without NMN, they only Can run 780 feet. Among them, NMN prolongs the cell aging cycle by supplementing NAD, provides energy for the cell mitochondria, and provides fuel for the longevity gene Sirtuin, which in turn helps repair and maintain cell health.
Diabetes is a chronic disease that becomes more common with age. About one in ten people in Hong Kong suffers from diabetes. In 2021, the Centers for Disease Control and Prevention (CDC) said that about 25% of people over the age of 65 in the world have diabetes. Nerve damage and even dementia. Study finds NAD levels lower in diabetics than in the general population, can taking NMN help them? In 2020, scientists at the University of Maryland School of Medicine published a study showing that NMN promotes neuron protection, survival and regeneration in the brain’s hippocampus. The main function of the hippocampus is to be responsible for memory and cognition, and the research results show that the cognitive function of diabetic mice is maintained in a stable state after taking NMN, indicating that NMN may alleviate the brain damage and cognitive impairment associated with diabetes.
FAQs
A 750ml bottle of red wine contains about 1~7mg of resveratrol, and the content of each supplement is 600mg. If the average content is 3mg, we need to drink 200 bottles of 750ml red wine to reach 1 capsule of resveratrol. effect of supplements.
There are indeed a lot of foods, such as broccoli, tomatoes, beef, etc., but the content is very small. According to statistics, eating 16 kg of NMN-containing vegetables can only absorb 160 mg of NMN. Taking a person weighing 60kg as an example, a person aged 50 or below needs to consume 500mg of NMN per day; those over the age of 50 absorb 750mg of NMN per day. It can be seen that it is difficult to supplement the NMN required by the body in the daily diet and convert it into NAD. It is recommended to supplement the body with NMN from supplements.
Due to the large size of NAD molecules, they cannot be taken directly and absorbed by cells, nor can they be stored in a stable state at room temperature. However, we can increase the level of NAD by supplementing with NR or NMN. Both NR and NMN are precursors of NAD, and the molecules are smaller and easier to be absorbed by cells. Studies have shown that taking NAD precursors can increase NAD levels by up to 60%.
According to the latest research report, for an adult, it is necessary to take almost 2000mg of NR to effectively increase NAD; compared with NMN, only need to take a dose between 200-400mg to achieve the same effect, and NMN can also reduce mitochondrial diseases and increase endurance, so it's better.
Resveratrol comes from natural foods and has relatively low side effects. Resveratrol is used in large doses between 2.5 g and 5.0 g, which may cause mild gastrointestinal symptoms, but generally do not take such a large amount, so it is not necessary to take too much. Worry. However, because high-dose resveratrol may have anticoagulant effects, it should not be taken with related anticoagulant drugs such as heparin or warfarin. In addition, if you are pregnant, breastfeeding and suffering from estrogen-sensitive diseases (such as breast cancer, ovarian cancer, endometriosis, uterine muscle cancer), it is best to consult your doctor first.
The aforementioned NMN is one of the derivatives of vitamin B3. A small number of people who have allergic reactions to high doses of vitamin B may also have allergic reactions when taking NMN.
Occasionally forgetting to take it does not affect long-term results. If you have been taking it for a period of time and then stop taking it completely, your health will not deteriorate without the disease, and your physical function will be adjusted and improved based on your living habits and environment at that time, according to the normal aging speed. Metabolism without worrying about rebound.
Scientific research has found that resveratrol can activate the SIR gene to help maintain cell health and prolong its lifespan, but resveratrol alone cannot maximize the function of the SIR gene. Professor Dr David Sinclair of Harvard Medical School proposed that if the SIR gene is regarded as a car, resveratrol is the accelerator pedal, and NMN is the fuel of the car to help the SIR gene maintain its operation. Not one.
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