What are sirtuins?

Sirtuins are a group of 7 proteins that have long been the focus of longevity research. They influence many different signaling pathways in the body and have been shown in studies to prolong life by more than 30%. This life extension is achieved through 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 them is to find out more about these potentially life-prolonging proteins and their activation.

We show you how sirtuins work at a molecular level, how you can 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 epigenetics. The prefix epi means "over" or "on" and that's exactly what it's all about. Every cell in our body has the complete blueprint of all proteins, rolled up in the DNA, but we never need the entire blueprint.

Imagine the whole thing as a huge manual and parts of this manual are pasted over with colored paper so that you can't read these sections. This is roughly how you can imagine methylation. These are chemical processes that determine which "building instructions" (proteins) are read and produced in a cell and which are not.

Depending on the cell type, this pattern looks very different. A heart muscle cell requires different proteins than a liver cell, even though in theory they both have the building instructions for all proteins. However, this pattern (epigenetics) of which proteins are read and which are not is not rigid, but highly variable.

Our lifestyle has an enormous influence on our epigenetics. Sport, smoking, sleep, mental health - all of these are reflected in epigenetics.

Sirtuins and epigenetics

However, if this pattern is disrupted, e.g. in old age due to increasing oxidative stress, the methylation pattern can change in such a way that the cell produces the wrong proteins and thus becomes non-functional. To stay with the example, if a liver cell can no longer reliably produce the proteins it needs for its detoxification task, it becomes non-functional and, in the worst case, can degenerate.

This type of damage increases with age. And this is where sirtuins come into play. Researchers have discovered that certain proteins, including sirtuins, can have a protective effect . If we manage to get our body to produce more sirtuins, this has positive effects. We will now explain exactly how.

Knock-out mice - how do scientists find out the function of genes?

Have you ever wondered how researchers can even find out how certain genes or proteins work?

One well-known method is the so-called knock-out mouse. Advances in genetic engineering have enabled scientists to precisely cut out individual genes. This has also been done with the sirtuins, with sometimes drastic results. Without the sirtuin genes (i.e. also without the sirtuin proteins), many mice never 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 activate so-called promoter sites. You can think of this as a boost in production. If the promoter is activated, in this case, more sirtuins are produced. The interesting thing about this. The animals lived longer and were healthier.

Now we have laid the foundations. Sirtuins appear to play an important role in longevity. They are described as one of the four major longevity pathways. The next step is to find out how we can activate the sirtuins (without genetic manipulation) and which members of the sirtuin family are responsible for which effect.

The Sirtuin family

When we talk about the sirtuins, we can distinguish between the sirtuin genes and the sirtuin proteins. The blueprint for the individual family members is hidden in the genes. Seven of them are known so far. What do they do and where do we find them?

Sirtuins are so-called NAD-dependent histone deacetylases. If you haven't studied biochemistry, this will probably mean nothing to you. But don't worry, we'll introduce you to this complex topic. Let's start with NAD.

Sirtuine and NAD - an effective duo

NAD is short for nicotinamide adenine dinucleotide. It is an important co-enzyme in our body, which we find above all in the power plants of our cells, the mitochondria. Sirtuin proteins need NAD as a kind of fuel in order 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 ageing process. NAD metabolism is a complex topic in its own right. To cut a long story short, NAD levels fall with age. Researchers see this as one of the main reasons for ageing.

Sirtuins and epigenetics

We have now been able to clarify in the first step that sirtuins require NAD. But what does the rest of "NAD-dependent histone deacetylases" mean?

Let's start with the histones. These proteins are important for storing DNA in the cell nucleus in the most space-saving way possible. An analogy to this would be hair curlers. The DNA (the hair) is wrapped several times around the curlers (histones) and stored in this way.

Do you remember methylation? The color-coded sites 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, e.g. by acetyl groups. Depending on the labeling, the rolled-up DNA is easier or more difficult to detach from the histone. This allows our body to influence which proteins are more likely to be produced.

This is precisely where the sirtuins intervene. As NAD-dependent histone deacetylases, the sirtuins remove acetyl groups from the histones. In this way, they influence which genes are read in the cell - and which are not.

Sirt 1 - the "oldest" member of the family

When we talk about 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 function. We have already used the complicated term NAD-dependent histone deacetylases. All sirtuins have this function. However, acetylation is not the only way to provide histones with biochemical markers. The details are beyond the scope of this article, but you can remember that Sirt 6, for example, also has other capabilities.

For example, studies have shown that high Sirt 1 levels can lead to a number of health benefits. But how can you activate sirtuins? One of the most potent Sirt1 activators is the resveratrol contained in red grapes. resveratrol. Dr. David Sinclair one of the most renowned researchers on ageing, has focused his studies in particular on the effect of resveratrol on sirtuins.

Another way to activate the sirtuins is by fasting . More on this later.

Sirt 6 - a potential candidate for a longer life

Sirt 6 was one of the last molecules to be discovered. Alongside Sirt 1, the activation of Sirt 6 has shown the most promising results in ageing research. Sirt 6 helps to keep DNA stable and protect it from age-related damage. When activated, Sirt 6 also reduces inflammation and improvesblood sugar control.

In mouse experiments, the animals with low Sirt 6 activation aged significantly faster. In contrast, the mice with a high Sirt 6 level were healthier and lived longer. So how can we activate Sirt 6? Selected secondary plant substances can do this, albeit only in high concentrations. Another possibility is brown seaweed (Fucus dichitus), which led to strong Sirt 6 activity in studies.

Sirtuins and oxidative stress - what makes us more vulnerable in old age

There is a delicate balance in our body. The various metabolic processes constantly generate free oxygen radicals (ROS), which can damage our DNA. For this reason, there are so-called ROS scavengers, e.g. glutathionewhich help to prevent too much damage from occurring.

The older we get, the more this balance tips towards ROS. More damage occurs in the DNA, which can no longer be repaired in time.

Sirtuins can help here by activating signaling pathways within the cell that ensure a more stable metabolism.

Inflammation - a broad 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 brief look at what inflammation actually is. Our immune system consists of a whole range of specialized cells. Since all these cells have no eyes, ears or mouths with which to orient themselves, they rely on a different kind of communication. Chemical messengers, also known as mediators. These include histamine, for example.

If we injure ourselves, e.g. through a small skin incision, many inflammatory signals are immediately released at this site, which in turn attract immune cells. Such inflammation is therefore helpful for our health.

However, there are also "quieter" sources of inflammation. Abdominal fat, for example, releases inflammatory hormones and mediators that are associated with some diseases. In old age, so-called "inflammaging" plays an important role as one of the 12 hallmarks of ageing.

As you can see, inflammation plays a major role and there are many subcategories behind the term. Many diseases are based on an inflammatory process that has gone off the rails, e.g. irritable bowel syndrome, but also allergies and inflammatory joint diseases. Here there are possible approaches that activation of the sirtuins could help to get the symptoms under control.

Sirtuins and autoimmune diseases - new therapeutic approaches for the future?

In autoimmune diseases, the immune system overreacts and attacks the body's own structures, mistaking them for foreign pathogens. One of these diseases is the widespread Hashimoto's thyroiditis, in which the immune system gradually destroys the thyroid gland.

In a recent study, researchers have discovered that underactivation of Sirt 1 may contribute to the development of Hashimoto's disease. This results in a possible new approach for the treatment of the widespread thyroid disease.

Sirtuin diet (Sirt-food) - Adele's secret to losing weight

So how can you activate the sirtuins? One way is through a range of secondary plant substances such as resveratrol or luteolin. In addition, a reduced food intake in the form of fasting can activate the sirtuins, as can sport.

According to British singer Adele, she has lost several kilos on a special Sirtuin diet. The idea behind it is to activate Sirt 1 through a combination of different foods and calorie restriction, as this is mainly responsible for the positive changes.

The foods in the Sirtuin diet are all rich in phytochemicals. These 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 (have an anti-inflammatory effect)
• Parsley, thyme (contain apigenin)
• Onions and capers
• Red wine (contains resveratrol)
• Black and green tea (contains EGCG)
• Olive oil (contains healthy fats)
• Apples

What happens at the molecular level during fasting?

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 to eliminate "zombie cells", so-called senescent cells. These are cells that are in an intermediate state between functional 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 ageing 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 the subject of sirtuins

The sirtuins could represent a breakthrough in longevity research. With them, we have found a signaling pathway in the body that is most likely responsible for some of the signs of aging. If we manage to better understand the sirtuins and find out how we can effectively activate them in old age, then promising new paths for our longevity will open up.