The Sirtuins are a group of 7 proteins that have long been the focus of longevity. They influence many different signaling pathways in the body and in studies have been able to lead to a life extension of more than 30%. This life extension is achieved through various factors. Active sirtuins protect our DNA from damage, combat excessive inflammatory reactions and can help our body sort out cells that are no longer functional. For this reason, the science behind them is to find out more about these potentially life-extending proteins and how they are activated.
We'll show you how sirtuins work on 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 epigentics anyway?
Before we delve deeper into the field of sirtuins, we need a bit of background knowledge about epigenetics. The prefix Epi means something like “over” or “on top of” and that’s exactly what it’s about. Although every cell in our body has the complete blueprint of all proteins rolled up in DNA, we never need the entire blueprint.
Imagine this whole thing as a giant manual, with parts of the manual covered in colored paper so you can't read those sections. You can roughly imagine methylations. 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 completely 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. This pattern (the epigenetics) of which proteins are read and which are not is not rigid, but rather highly variable.
Our lifestyle has an enormous influence on our epigenetics. Exercise, smoking, sleep, mental health – all of this is reflected in epigenetics.
Healthy nutrition can have a significant positive influence on our epigenetics.
Sirtuins and epigenetics
However, if this pattern gets mixed up, e.g.b As we age due to increasing oxidative stress, the methylation pattern can change in such a way, that the cell produces incorrect proteins produced and therefore becomes inoperable. 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 play. Researchers have found that certain proteins can have a protective effect , including the sirtuins. If we manage to get our body to produce more sirtuins, then this will have positive effects. We'll now explain how exactly.
Knock-out mice – how do scientists find out the function of genes?
Have you ever wondered how researchers can find out how certain genes or proteins work?
A well-known method is the so-called Knock-Out Mouse. Advances in genetic engineering allow scientists to precisely edit out individual genes. This has also been done with the sirtuins, with sometimes drastic results. Without the sirtuin genes (that is, 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 does it look like the other way around? What happens when there are a lot of sirtuins? There is a trick in research here too. 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 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 referred to as one of the four most important longevity paths . 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
If we talk about sirtuins, then we can distinguish between the Sirtuin genes and the Sirtuin proteins. The blueprint for the individual family members 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 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 start with NAD.
Sirtuins and NAD – an effective duo
NAD is the short form of nicotinamide adenine dinucleotide. It is an important co-enzyme 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.
So 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 its own, complex topic. To make a long story short, NAD levels decrease with age. Researchers see this as one of the main reasons for aging.
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Sirtuins and epigenetics
In the first step we have now been able to clarify that sirtuins require NAD. But what does the rest of “NAD-dependent histone deacetylases” mean?
First to the Histones. These proteins are important for storing DNA in the cell nucleus in as little space as possible. An analogy would be hair curlers. The DNA (the hair) is wrapped several times around the curlers (histones) and stored in this way.
Do you remember the Methylations? The colored spots in the DNA blueprint that ensure that certain proteins are not produced? Well, it There is another regulatory level above this. The histones can also be produced by molecules, e.g.b by acetyl groups. Depending on the marking, the rolled-up DNA is easier or more difficult to detach from the histone. This means our body can once again influence which proteins are more likely to be produced.
This is exactly where the Sirtuins intervene. As NAD-dependent histone deacetylases, sirtuins remove acetyl groups from histones . They therefore 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 origins. 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 already had the complicated word NAD-dependent histone deacetylases. All sirtuins have this function. However, acetylation is not the only way to provide biochemical markers to histones. The details are beyond the scope of this article, but you can remember that e.g.b Sirt 6 also has other abilities.
High Sirt 1 levels, for example, have been shown to lead to some health benefits in studies. But how can you activate Sirtuins? One of the most potent Sirt1 activators is the Resveratrol contained in red grapes. Dr. David Sinclair , one of the most renowned aging researchers, has focused his studies in particular on the effect of resveratrol on sirtuins.
Another way to activate the sirtuins is Fasting. More on this 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. In addition to Sirt 1, activation of Sirt 6 showed the most promising results in aging research. Sirt 6 helps keep DNA stable and protects it from age-related damage. In addition, when activated, Sirt 6 ensures reduced inflammation and was able to improve blood 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. How can we now activate Sirt 6? Selected secondary plant substances can do this, albeit only in high concentrations. Another possibility is brown seaweed (Fucus digitus), which in studies led to strong Sirt 6 activity.
Sirtuins and oxidative stress – which makes us more vulnerable as we age
There is a delicate balance in our body. The various metabolic processes repeatedly produce free oxygen radicals (ROS), which can damage our DNA. For this reason there are so-called ROS scavengers, e.g.b the Glutathione, which help prevent too much damage from occurring.
The older we get, the more this balance tilts towards ROS. More damage occurs in the DNA that can no longer be repaired in a timely manner.
Here the Sirtuins can help by activating signaling pathways within the cell that 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 have 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 with which to orientate themselves, they rely on a different type of communication. Chemical messengers, also called mediators. This includes, for example, Histamine.
If we hurt ourselves, e.g.b Through a small incision in the skin, a lot of inflammatory signals are immediately released at this point, which in return attract immune cells. Such inflammation is therefore helpful for our health.
Now there are also “quieter” sources of inflammation. For example, abdominal fat releases inflammatory hormones and mediators that are linked to some diseases. In old age, the so-called “Inflammaging” plays as one of the 12 Hallmarks of Aging an important role.
You see, Inflammation plays a big role and there are many subcategories behind the term. Many illnesses are caused by an inflammatory process that has gone awry, e.g.b irritable bowel syndrome, but also allergies and inflammatory joint diseases. There are possible approaches here that activating the sirtuins could help to get the symptoms better 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, which it mistakenly believes to be foreign pathogens. One of these diseases is the widespread Hashimoto thyroiditis, in which the immune system gradually destroys the thyroid.
In a recent study, researchers found 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 widespread thyroid disease.
Sirtuin diet (Sirt-food) – Adele's secret to losing weight
How can you now activate the sirtuins? This goes through a series of secondary plant substances, like Resveratrol or Luteolin. In addition, reduced food intake in the form of fasting can activate the sirtuins, as can exercise.
The British singer Adele according to herself has lost several kilos with a special Sirtuin diet . The idea behind it is to activate Sirt 1 through the combination of different foods and calorie restriction , as this is mainly responsible for the positive changes.
Foods that appear in the Sirtuin diet are all rich in secondary plant substances. 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 (act 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 during fasting at the molecular level?
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, to be sorted out. 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 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 influenced and what types of fasting there are.
Conclusion on the topic of sirtuins
The sirtuins could represent a breakthrough in longevity research. We used them to find a signaling pathway in the body that is most likely responsible for some of the symptoms of aging. If we manage to understand sirtuins better and find out how we can effectively activate them even in old age, then promising new avenues for our longevity will open up.
