The Sirtuins are a group of 7 proteins that have been in the spotlight for longevity for some time. They influence many different signaling pathways in the body and have been shown in studies 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 responses , and can help our body sort out non-functional cells. For this reason, the science behind it is focused on learning more about these potentially life-extending proteins and their activation.
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 dive deeper into the field of sirtuins, we need a bit of background knowledge about epigenetics. The prefix Epi means something like "above" 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 DNA, but we never need the entire plan.
Imagine the whole thing as a huge instruction manual, and parts of this manual are covered with colored paper, so you can't read those sections. This is somewhat how you can think of 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 type of cell, this pattern looks completely different. A heart muscle cell requires different proteins than a liver cell, even though both theoretically possess the building instructions for all proteins. This pattern (epigenetics), which proteins are read and which are not, is not rigid but highly variable.
Our lifestyle has a tremendous impact on our epigenetics. Exercise, smoking, sleep, mental health – all of this is reflected in epigenetics.
Healthy nutrition can significantly positively influence our epigenetics. Sirtuins and epigenetics However, if this pattern gets disrupted, due to increasing oxidative stress with age, then the methylation pattern can change in such a way that the cell produces incorrect 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, then it becomes non-functional and can degenerate in the worst case. This type of damage increases more and more 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, it will have positive effects . How exactly, we will explain to you now.
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. Through advances in genetic engineering, scientists can precisely cut out individual genes. This has also been done with the sirtuins, with sometimes drastic results. Without the sirtuin genes (that is, also without the sirtuin proteins), many mice never reached adulthood. This was the first hint 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 present? There is also a trick in research here. One can activate so-called promoter sites. You can think of it as a boost in production. When 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 seem to play an important role in longevity.They are referred to as one of the four most important 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 sirtuins, we can distinguish between sirtuin genes and sirtuin proteins. The genes hide the blueprint for the individual family members. Seven are known so far. What do they do now and where can we find them? Sirtuins are so-called NAD-dependent histone deacetylases. If you haven't studied biochemistry, this probably won't mean much to you. But don't worry, we'll help you understand this complex topic. 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 mainly find in the powerhouses 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, as it plays an important role in the aging process. The NAD metabolism is a complex, multifaceted topic. To make it short, the NAD levels decrease with 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, let's talk about the histones. These proteins are important for storing DNA as compactly as possible in the cell nucleus. An analogy would be curlers.The DNA (the hair) is wrapped multiple times around the curlers (histones) and stored that way.
Do you still remember the methylations? The color-coded spots in the blueprint of the DNA that ensure that certain proteins are not produced? Well, there is another regulatory level above that. The histones can also be marked by molecules, z.B. such as acetyl groups. Depending on the marking, the coiled DNA can be more easily or more difficultly released from the histone. This allows our body to influence which proteins are produced more readily.
This is exactly where the sirtuins come into play. As NAD-dependent histone deacetylases, the sirtuins remove acetyl groups from the histones. Thus, 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 commonly found in the cell nucleus but also in the cell fluid, while Sirt 3 and Sirt 4 are in the mitochondria – and in their function. We have already mentioned the complicated term NAD-dependent histone deacetylases. All sirtuins have this function. However, acetylation is not the only way to mark histones with biochemical markers.The details would exceed the scope of this article, but you can remember that Sirt 6 also possesses other abilities. High Sirt 1 values, for example, could lead to some health benefits in studies. But how can you activate sirtuins? One of the most potent Sirt1 activators is the resveratrol found in red grapes. Dr. David Sinclair, one of the most renowned aging researchers, has particularly focused on the effect of resveratrol on sirtuins in his studies. Another way to activate sirtuins is through fasting. More on that later.
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Sirt 6 – a potential candidate for a longer life
Sirt 6 was discovered as one of the latest molecules. In addition to Sirt 1, the activation of Sirt 6 showed the most promising results in aging research. Sirt 6 helps to keep DNA stable and protect against age-related damage. Additionally, Sirt 6 activation leads to reduced inflammation and was able to improve blood sugar control .
In mouse experiments, animals with low Sirt 6 activation aged significantly faster.Contrary to this, mice with a high Sirt 6 level were healthier and lived longer. How can we activate Sirt 6 now? Selected secondary plant compounds can do this, although only in high concentrations. Another option is brown seaweed (Fucus dichitus), which led to strong Sirt 6 activity in studies. Sirtuins and Oxidative Stress – what makes us more susceptible as we age In our body, there is a sensitive balance. Through various metabolic processes, free oxygen radicals (ROS) are constantly generated, which can damage our DNA. For this reason, there are so-called ROS scavengers.Glutathione, which help to prevent excessive damage. The older we get, the more this balance shifts towards ROS. More damage occurs in the DNA that can no longer be repaired in time. 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 concretely? How can a substance be anti-inflammatory? To understand 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, and mouths with which they can orient themselves, they rely on a different kind of communication. Chemical messengers, also called mediators. This includes, for example, histamine.
If we injure ourselves, z.B. through a small cut in the skin, then many inflammation signals are immediately released at that spot, which in turn attract immune cells. Such an inflammation is therefore helpful for our health.
However, there are also “quieter” inflammation sites. For example, abdominal fat releases inflammation hormones and mediators that are associated with certain diseases. In old age, the so-called "inflammaging" plays an important role as one of the 12 hallmarks of aging .
You see, inflammations play a significant role, and behind the term are many subcategories. Many diseases are based on a disrupted inflammatory process, z.B. irritable bowel syndrome, but also allergies and inflammatory joint diseases. Here, there are possible approaches that activation of sirtuins could help manage the symptoms better.
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 perceives as 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 found that underactivation of Sirt 1 may contribute to the development of Hashimoto. This presents a potential new approach for the treatment of the common thyroid disease.
Sirtuin Diet (Sirt-food) – Adele's Secret to Losing Weight
How can you now activate the Sirtuins? This can be done, on the one hand, through a number of secondary plant compounds, such as Resveratrol or Luteolin. In addition, a reduced food intake in the form of fasting can activate the Sirtuins, just like exercise.
The British singer Adele has reportedly 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 are part of 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 (have 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 on a molecular level?
Fasting is also an important aspect of the Sirtuin diet (also known as the sirt-food diet). Due to the lack of nutrients, the cells are put into a kind of "survival mode". The sirtuins are activated by this energy deficiency and ensure that the old cells are made as fit as possible again.
The sirtuins can also help to sort out "zombie cells," so-called senescent cells, which are in a state between functional and dead. We have elaborated on the exact background in two other posts.Once 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 will look at whether there are medical reasons for fasting, which molecular pathways are influenced, and what types of fasting exist.
Conclusion on the topic of sirtuins
Sirtuins could mean 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 sirtuins and find out how we can effectively activate them even in old age, then promising new paths for our longevity open up.
