Article discussing ageing, epigenetics, sirtuins, fasting, exercising, resveratrol and NMN

The following article was written by Dr. med. Helmut B Retzek, and breaks down quite a complicated subject into smaller sections that are simpler to understand. It is essentially detailed podcast notes for the YouTube video here.
The original article is here (archived version is here). The original article was written in German, and this has been translated into English below. Some errors due to the translation are present.

Summary : Loss of epigenetic information is central to the cellular aging process.
Remedy: Fasting / Sport / Metformin / Resveratrol / NADH induce sirtuins, which are central to the maintenance of epigenetic information.

Anti-aging researcher: Dr. med. David Sinclair

One of the scientists I have unfortunately overlooked so far is Dr. Ing. David Sinclair.

The long car trips to the courses (eg currently Faszien Distorsions Model Training in Wolfenbüttel) allow me to listen to many lectures by interesting current scientists. Dr. Sinclair was an exciting new discovery for me!

Dr. Sinclair is an Australian, geneticist and scientist who has been researching at Harvard Medical School since 2004 and has also discovered the so-called “longevity genes” sirtuins .

Dr Sinclair wrote his research results in a new book, which has just come out and will soon be published in Germanäre-Lifespan-ebook/dp/B07QNZRYGY?SubscriptionId=AKIARIZDFMFKIWAWQFHK&tag=umfassengesun-21&linkCode=alb&camp=2025&creative=165953&creativeASIN=B07QNZRYGY

The biology of aging

meanwhile one identifies about 8 different typical changes during the aging process:

Telomeres, for example, become shorter, mitochondria become less and more inactive, cell division stops, cells become zombi cells (senescence), …

Dr. Sinclair wonders in his research: why does everything actually happen?

(c) Pixabay Free Photos Clock Clock Face

What causes these aging processes to take place at all? Is there a higher-level mechanism?

Sinclair develops the theory of information loss of aging .

He says that during the aging process, the body loses specific information that causes the above-cited aging characteristics to take place.

Actually, that’s not all that complicated to understand. Sinclair:

Digital and analog “genetic information”

According to Sinclair, we are shaped and trained by 2 genetic information as we are: the digital genetic information and the environmental-dependent analog epigenetic .

DNA stores our genetic information in the form of 4 different letters. The sequence of these letters determines the expression of the proteins encoded thereby exactly, ie " digital ".

(c) uploaded to Researchgate by Nithyha Parameswaran

However, the translation of our genetic material information is influenced by many external influences, this is called epigenetics.

Packed away is unattainable

It makes a difference whether the DNA is freely available or wrapped tightly on Histone, where it is virtually inaccessible and shut off.

Specialists already know: DNA methylation and histone acetylation determine whether a gene is free and unwound, or whether it is wrapped tightly packed in histones.

Which genes are now exactly active and which are packed away and turned off determines the so called epigenetics.

Only the packing state of the DNA determines the cell type

All cells actually have exactly the same digital genetic information,

in liver cells , only the liver cell genes are released, in nerve cells only the nerve cell genes .

The activation of genes is also called “expression”, liver cells “express” certain liver-typical proteins because their DNA segments (genes) have not been packed away by being wound up on histones.

Of course, these individual characteristics should also be transferred to the daughter cells.

Epigenetics is co-determined by environmental factors = analog

These epigenetic influences are gradual and are to a great extent also influenced by external factors. This epigenetics changes constantly, depending on the time of day, the pattern of movement, diet, stress, etc., etc. - so it is constantly in flux, hence the term “analogue information”, while the digital DNA information remains fixed.

Loss of epigenetics leads to the forms of degeneration we call age

After Dr. Sinclair cells and their descendants increasingly lose their epigenetic information in the course of their 80 years of life and thus begin an unregulated life of their own or lose their ability to divide correctly or function correctly and eventually become zombi cells ( Seneszens ).

Why the loss of epigenetics?

strong cell stress eventually leads to chromosome breaks . To survive, the cell must repair the DNA. However, for this repair, the DNA must be handled by the histones. Many cells lose this epigenetic information that was stored in the Aufwicklungs pattern.

So the nerve cells slowly lose their identity as nerve cells, just like the liver cells.

Term Precision: Genes are DNA sections with genetic information. With the help of protein synthesis , a protein is then generated from this information. The proteins are the actual machines that do any work in the body. Their structure is coded by the DNS information. Therefore, proteins are often called imprecise genes or equated. What exactly meant is given by the context:

The sirtuin gene is the coding DNA sequence from which the sirtuin protein is expressed (produced).

Proteins are divided into structural proteins (eg collagen or histone) and enzymes. The enzymes accelerate the chemical reaction millions of times, are quasi-small chemical factories.

Certain proteins - sirtuins - are responsible for unpacking the DNA as well as packing the DNA. If we have many of these proteins or they are very active, DNA repair can be much more efficient and faster, and we do not lose so much epigenetic packaging information, which means that the cell ages less and retains its exact expression type for longer.

These proteins can be stimulated and activated from the outside, all anti-aging measures are ultimately based on this mechanism:

Exercise, nutrition, starvation → make all these enzymes active, alert and let the cell produce more of these important repair enzymes.

Sirtuins are the packaging masters and determine longevity

In order to pack DNS away the histones have to be prepared for it. Sirtuins are proteins that activate the histones by histone acetylation. If we have little sirtuins, the DNA is also packaged poorly, thus losing more and more of its epigenetic properties.

Dr Sinclair has been studying sirtuins for 25 years. They are activated and energized by 2 substances

  • NAD +
  • resveratrol

Together, these substances work ingeniously and keep the cells younger.

From his studies on yeasts, he was able to show that the sirtuins are expressed by “threats” and activated. The more stress for the cells, the more sirtuins become active in order to protect the cell against chromosome breaks and stress-related damage.

Exactly the same thing they have found in the higher living beings: stress activates these longevity genes:

Hungry - also intermittent fasting (omit a meal) - several times a week out of breath due to sports.

What to do to delay aging - dr. Sinclair promises 120 years

So what can I do after Sinclair to make the best possible provision here? His book comes in German in 2 weeks, as long as I’m still waiting, also I read a lot faster in German than in English. Here therefore the succus of Dr. Sinclair I have extracted from several Youtubes:

Level 1: Turn genes on and off through life style

Fasting is the ultimate anti-aging program

We are genetically engineered to switch between times of abundance and times of starvation . During periods of hunger, the body goes into maintenance mode , begins to regenerate and to get rid of the superfluous by “eating it up” (autophagy).

In filling times, every organism begins to grow and multiply.

The necessary control systems are already present in the bacteria and have not changed until high to the human being, life always fluctuated between abundance = increase and hunger = maintenance / regeneration to survive as far as the next fullness phase.

Exercise several times a week - get out of breath

Level 2 - Pack genes away in the long term

Sirtuins pack up superfluous genes. Here resveratrol is used as a sirtuin activator, NMN as a sirtuin cofactor and metformin as a further sirtuin inducer.

This does not result in permanent DNA protection, but one can expect to keep taking these substances over and over again in a pulsatile manner, benefiting greatly and then getting an additional 10 years

Dr. Sinclair takes every night

  • 1000mg metformin
  • 1000mg NMN
  • 500mg Resveratrol

In addition, he leaves one - a lunch several times a week, on breakfast he renounces completely.

Level 3 - “Deep level of aging”

Methylation Status of DNA

The older you get, the more DNA is methylated. The methylation of DNA leads to reduced expression of their proteins.

One has “machine learning” - ie neural networks with the methylation patterns of 1000 of humans and their date of death fed and thus get an apparatus with which one can determine the current genetic age with high probability .

If you could bring down the DNA methylation that would take at least 10 years to live. After these 10 years, the DNA is then methylated again, then you can do this procedure again and get back 10 years.

There are currently no medications or tools available, but research is on this very point and they can reprogram mice already accordingly, the solutions are likely to come in the next few years.

In-depth information

from the Youtube lectures I have extracted information that did not fit in the context above or would have expanded the text too much, but are interesting:

3 genes regulate the lifespan and aging

  • mTOR - measures whether enough sugar or amino acids are present to make cell division. The fewer amino acids are present, the less cell division (the longer one lives because one gets along with the limited number of cell divisions longer). Excess of amino acids and everything sprouts out, multiplies, grows. Therefore you have to take care with Carnivorismus or Ketogener diet with the total protein content (fat!) And possibly additionally take hydrolyzed collagen.
  • AMPK - Energy Sensor - measures commonly available energy (in the form of ATP). The less energy, the more AMPK switches the organism into maintenance mode
  • Sirtuins - the maintenance proteins - unwrap DNA from their solid packaging (histones), making repair programs much easier. The older an organism, the less sirtuin, the less DNA can be unpacked and re-packed and the cell loses its fixed and important individual programs.

ad metformin

Metformin attacks the AMPK and thus gives the cells the signal "It is hungry ". We have already heard that this will switch to the regeneration state .

At the same time , metformin poisons a part of the mitochondria in the cells because it irreversibly inhibits the respiratory chain complex 1 . The body now responds to this stress with the new production of mitochondria and overall there are more functioning mitochondria available than before taking metformin.

It is called a “healing stress” and Hormesis. Similarly, for example, cold showers.

The least important feature of metformin is the stabilization of blood sugar levels, which has been used on millions of diabetics for decades, so we know the effects and side effects of this drug very well and have noticed that metformin-supplied diabetics live with cancer much longer than without metformin, why metformin has become widely used in integrative oncology.

Metformin increases insulin sensitivity

Metformin it increases the effect of sport on the neogenesis of mitochondria. Many athletes now take metformin before their training .

Metformin is increasingly being used by many people as a longevity drug.

NADH - incredible sirtuin fuel

one can take NAD or NMN or NR, which are all well absorbed and increase the NADH level.

NMN raises the energy levels so much that old mice volunteer to walk more and continue to run than young mice. You also get values ​​from old people like young marathon runners.

At the same time it is a fantastic activator for sirtuins.

I bought my NMN here in the UK , with a measuring spoon you will not get enough, it works from 850mg (kinesiologisch test).

What does Dr. Sinclair: Inside Tracker - blood levels

30 blood values ​​are measured here

Gen test for mutations - 99, -

Telomere length measurement

What is the most important thing

just be a little hungry again and again! Dr. Sinclair does not have breakfast, always omits a lunch.

Resveratrol and NMN

Sirtuins are put into a highly active state by resveratrol. In order to function at all, the sirtuins need NADH +, which he supplies in the form of nicotine mono-nucleotide.

In principle, 1000 years would be possible

my dr. Sinclair, it’s because of the cell repair machinery that slowly breaks down and stops working as of 40 LJ. For example, a whale - a warm-blooded self-conscious mammal - is several hundred years old, a mouse only two years old. As a rule, the organisms die shortly after the end of their reproductive phase and we humans are naturally due to the many starvation phases and hostile predators on 40 years aligned.

Stress is helpful - Hormesis

you want pulsatile stress. Fasting but not starving or starving. Repeated stress leads to “preparation” of the cells.

Calorie restriction was the wrong way

You can let mice live 30% longer by giving them about 30% less food. But they are permanently stressed and unhappy. The same thing happens to a person under calorie restriction.

However, if you give mice food only every other day then they will be full on the food days and have a total of about 90% of the calories they would eat if they were offered food on a daily basis. Nevertheless, they live 30% longer!

but intermittent fasting is the solution

This leads to the concept of intermittiernden fasting, longer breaks (at least 18h) which are repeatedly introduced once or several times a week.

Induce brown fat through cold showers

Brown fat is full of mitochondria and tells the body somehow - that’s not yet understood - to be especially healthy. Because of that, Dr. Sinclair once a week in the sauna and then cooled for 4 minutes in the cold pool with less than 4 ° C from.

The loss of cold at night is thought to be responsible for diabetes. We do not have to “heat” the body at night and still eat much more.

Shinya Yamanaka 2012 Nobel Prize

Dr. Yamanaka received the 2012 Nobel Prize for stem cell work. With 4 simple genes - as he has discovered - one can produce fresh juvenile stem cells from old cells. From these stem cells you can breed completely new healthy experimental animals with a normal life span. That means the information for Jungend is still hidden somewhere in the old cells.

Now it is enormously researched the DNS at least tw. to demethylate. In the laboratory one can already completely rejuvenate certain tissues of experimental animals.

Dr. Sinclair finished by pharmaceutical company

Pfizer has downsized Sinclair’s research into resveratrol. It has cost Sinclair almost the whole reputation and many years of work to show that Resveratrol actually docks directly to the sirtuins and activates them so they work much faster!

This approach is very common in the US or in this industry.

Father of dr. Sinclair

now at 80, he has been taking metformin for 10 years and, for some years, NMN and resveratrol. He lost at the age of 70, but now he is getting better and better. He’s traveling around the world again, taking on a new job and getting healthier.

Dr. med. Helmut B Retzek

General practitioner, multiple preventive medical, conventional medicine and complementary additional education . Scientific work and research contributions . Numerous articles and lectures . Extensive research in current medical research for the purpose of self-education and as a memory support.

Moderate dyslexia, therefore spelling and comma mistakes, please do not comment, who can not stand it please just do not read

Dr. med. Retzek’s Youtube - channel with testimonials etc.
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The Upper Austrian Medical Association criticizes large parts of this website as “intrusive, cheeky and the laity the impression of medical exclusivity awakening” .
This is by no means intended, the website is an intentional educational medium of Dr. med. Retzek, who shares his scientific Pubmed research with colleagues free of charge. That these researches could “violate the standing of the doctors” Dr. was. Not aware of it, he deeply regrets it and apologizes to the affected colleagues.