The Sirtuins are a group of 7 proteins, which have been the focus of longevity for some time. They influence many different signaling pathways in the body and have been shown in studies to life extension of more than 30%This life extension is achieved by various factors. Active sirtuins protect our DNA from damage, fight excessive inflammatory reactions and can help our body to sort out cells that are no longer functional. For this reason, the science behind finding out more about these potentially life-extending proteins and their activation is important.
We show you how sirtuins work on a molecular level, how to activate the health-promoting properties of sirtuins and what the sirtuin diet has to do with the singer Adele.
What is epigenetics anyway?
Before we delve deeper into the field of sirtuins, we need a little background knowledge about the epigeneticsThe prefix epi means something like "over" or "on top" and that's exactly what it's about. Every cell in our body has the complete blueprint of all proteins, rolled up in the DNA, but we never need the entire plan.
Imagine the whole thing as a huge instruction manual and parts of this instruction manual are covered with colored paper so that you cannot read these sections. This is roughly how you can imagine methylation. These are chemical processes that determine which "blueprints" (proteins) are read and produced in a cell and which are not.
Depending on the type of cell, this pattern looks very different. A heart muscle cell needs different proteins than a liver cell, even if in theory they both have the blueprint for all proteins. This pattern (epigenetics), which proteins are read and which are not, is not rigid, but highly variable.
Our lifestyle has a huge influence on our epigenetics. Sport, smoking, sleep, mental health – all of this is reflected in epigenetics.
A healthy diet can have a significant positive impact on our epigenetics.
Sirtuins and Epigenetics
However, if this pattern gets disrupted, e.g. in old age due to increasing oxidative stress, then the methylation pattern change like this, that the cell produces incorrect proteins and thus becomes dysfunctional. To stay with the example, if a liver cell can no longer reliably produce the proteins it needs for its detoxification task, then it becomes dysfunctional and, in the worst case, can degenerate.
This type of damage increases with age. And this is where the sirtuins come into playResearchers have discovered that certain proteins have a protective effect including the sirtuins. If we can do it, that our body produces more sirtuins, then this has positive effects. We'll explain to you now how exactly.
Knock-out mice – how do scientists find out the function of genes?
Have you ever wondered how researchers can figure out how certain genes or proteins work?
A well-known method is the so-called Knock-Out MouseThanks to advances in genetic engineering, scientists can precisely cut out individual genes. This has also been done with sirtuins, with sometimes drastic results. Without the sirtuin genes (that is, without the sirtuin proteins), many mice would never have reached adulthood. This was the first indication that sirtuins play an important role in the body.
And what about the other way around? What happens when there are a lot of sirtuins? Here, too, there is a trick in research. You can use so-called activating promoter sites. You can think of it as a boost in production. When the promoter is activated, in this case, more sirtuins produced. The interesting thing about it. The animals lived longer and were healthier.
Now we have laid the foundations. Sirtuins appear to play an important role in longevity. They are considered one of the four most important longevity pathways The next step is to find out how we can (without genetic manipulation) activating sirtuins and which members of the Sirtuin family are responsible for which effect.
The Sirtuin family
When we talk about sirtuins, we can distinguish between the Sirtuin genes and Sirtuin proteinsThe blueprint for each family member is hidden in the genes. Seven pieces are known so far. What are they doing now and where can we find them?
Sirtuins are so-called NAD-dependent histone deacetylases. Unless you've studied biochemistry, this probably won't mean anything to you. But don't worry, we'll explain this complex topic to you. To do this, we'll start with NAD.
Sirtuins and NAD – an effective duo
NAD is the short form of nicotinamide adenine dinucleotide. It is a important coenzyme in our body, which we find primarily in the power plants of our cells, the mitochondria. The Sirtuin proteins need NAD as a kind of fuel to carry out their biochemical reactions.
Without NAD, the sirtuins cannot function properly. You can remember this fact because it plays an important role in the aging process. NAD metabolism is a complex topic in its own rightTo put it briefly, the NAD levels in old age. Researchers see this as one of the main reasons for aging.
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Sirtuins and Epigenetics
Now we have clarified in the first step that sirtuins require NAD. But what does the rest of “NAD-dependent histone deacetylases” mean?
First of all, histones. This Proteins are important for storing DNA in the cell nucleus in the most space-saving way possibleAn analogy to this would be hair curlers. The DNA (the hair) is wrapped around the curlers (histones) several times and stored in this way.
Do you still remember the methylations? The colored spots in the DNA blueprint that ensure that certain proteins are not produced? Well, there is another regulatory level above that. The histones can also be marked by molecules, eg by acetyl groups. Depending on the label, the coiled DNA can be released more easily or more difficultly from the histoneThis allows our body to influence which proteins are produced.
This is exactly where the sirtuins come in. As NAD-dependent histone deacetylases, the sirtuins remove acetyl groups from the histonesThus, they influence which genes are read in the cell – and which are not.
Sirt 1 – the “oldest” member of the family
When we speak of age here, we mean the order in which the molecules were discovered.
The Sirtuin family has a total of seven members, which differ in their origin. Sirt 1 is most likely to be found in the cell nucleus but also in the cell water, while Sirt 3 and Sirt 4 are in the mitochondria – and in their functionWe have already mentioned the complicated term NAD-dependent histone deacetylases. All sirtuins have this function. However, acetylation is not the only way to label histones with biochemical markers. The details would go beyond the scope of this article, but you can remember that Sirt 6 also has other abilities..
For example, high Sirt 1 levels have been shown in studies to lead to some health benefits. But how can you activate Sirtuins? One of the most potent Sirt1 activators is the Sirt1 found in red grapes. resveratrol. Dr. David Sinclair , one of the most renowned researchers in aging, has focused in his studies particularly on the Effect of resveratrol concentrated on the sirtuins.
Another way to activate the sirtuins is Fast. More on that later.
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Sirt 6 – a potential candidate for a longer life
Sirt 6 was one of the last molecules to be discovered. Along with Sirt 1, the activation of Sirt 6 has shown the most promising results in aging research. Sirt 6 helps keep DNA stable and protect it from age-related damage.In addition, Sirt 6 reduces inflammation when activated and was able to blood sugar control improve.
In mouse experiments, animals with low Sirt 6 activation aged significantly faster. the mice with high Sirt 6 levels were healthier and lived longer. How can we activate Sirt 6? Selected secondary plant substances can do this, although only in high concentrations. Another possibility is brown seaweed (Fucus dichitus), which in studies led to strong Sirt 6 activity.
Sirtuins and oxidative stress – what makes us more vulnerable as we age
There is a delicate balance in our body. Through the various metabolic processes Free oxygen radicals (ROS) are constantly being produced, that can damage our DNA. For this reason, there are so-called ROS scavengers, e.g. the glutathionethat help prevent too much damage.
The older we get, the more this balance tips towards ROS. More damage occurs in the DNA that can no longer be repaired in time.
Here you can Sirtuins help by activating signaling pathways within the cell, which ensure a more stable metabolism.
Inflammation – a big term with a complex background
Sirtuins can reduce inflammation in the body. But what does that mean in concrete terms? How can a substance be anti-inflammatory?
To do this, we need to take a quick look at what inflammation actually is. Our immune system consists of a whole series of specialized cells. Since all of these cells do not have eyes, ears, and mouths to orient themselves, they rely on another form of communication. Chemical messengers, also called mediators. These include, for example, histamine.
If we injure ourselves, for example by making a small cut in the skin, a large number of inflammatory signals are immediately released at that location, which in turn attract immune cells. Such inflammation is therefore helpful for our health.
But now there is also "quieter" sources of inflammationFor example, abdominal fat releases inflammatory hormones and mediators that are associated with some diseases. In old age, the so-called “Inflammaging“ as one of the 12 Hallmarks of Aging an important role.
You see, inflammations play a major role and the term hides many subcategories. Many diseases are based on an inflammatory process that has gotten out of hand, e.g. irritable bowel syndrome, but also allergies and inflammatory joint diseases. There are possible approaches that activating sirtuins could help to better control the symptoms.
Sirtuins and autoimmune diseases – new therapeutic approaches for the future?
In autoimmune diseases, the body's own immune system overreacts and attacks the body's own structures, which it mistakenly considers to be foreign pathogens. One of these diseases is the widespread Hashimoto's thyroiditisin which the immune system gradually destroys the thyroid gland.
In a recent study, researchers found that underactivation of Sirt 1 may contribute to the development of HashimotoThis presents a potential new approach to treating this widespread thyroid disease.
Sirtuin Diet (Sirt-food) – Adele's Secret to Weight Loss
How can you now Activate Sirtuins? This is done through a series of secondary plant substances, How resveratrol or luteolinIn addition, reduced food intake in the form of Fast activate the sirtuins, just like sport.
The British singer Adele has a special Sirtuin diet lost several kilos. The idea behind it is through the combination of different foods and a calorie restriction to activate Sirt 1, because this is mainly responsible for the positive changes.
Foods that are in the Sirtuin Diet occurrences are all rich in secondary plant substancesThese include:
- Lots of green vegetables, such as spinach or broccoli (contains sulforaphane)
- Nuts (contain Omega 3 fatty acids)
- Tofu (contains spermidine)
- Turmeric, chili and cinnamon (work anti-inflammatory)
- Parsley, thyme (contain apigenin)
- onions and capers
- Red wine (contains resveratrol)
- Black and green tea (contains EGCG)
- Olive oil (contains healthy fats)
- apples
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What happens on a molecular level when you fast?
Fasting is also an important aspect of the Sirtuin diet (also known as the sirt-food diet). The lack of nutrients puts the cells into a kind of “survival mode”. The sirtuins are activated by this lack of energy and ensure that the old cells are made as fit as possible again.
The sirtuins can also help “Zombie cells”, so-called senescent cells, be sorted out. These are cells that are in an intermediate state between functioning and dead. We have explained the exact background in detail in two other articles. Firstly, the exciting aspect of “zombie cells” and what they have to do with aging and the second article gives you a deeper insight into the world of fasting. We look at whether there are medical reasons for fasting, which molecular signaling pathways are affected and what types of fasting there are.
Conclusion on Sirtuins
Sirtuins could represent a breakthrough in longevity research. With them, we have discovered a signaling pathway in the body that is most likely responsible for some of the signs of aging. If we can better understand sirtuins and find out how we can activate them effectively even in old age, then promising new ways for our longevity will open up.
