All cells use a variety of quality control mechanisms to ensure the functionality and stability of their respective protein diversity. In the scientific community, this process is called proteostasis. Proteostasis consists of the two terms proteome (totality of proteins that a cell can produce) and homeostasis (balance) together. In the best case, the proteins of a single cell are always correctly folded and always present in the right amount. Despite all noble efforts, our body does not manage to guarantee this optimum. In this article, we will show you what aging and some age-related diseases have to do with a loss of proteostasis to do with.
From DNA to Chain to Protein
First, we need to get a better understanding of the molecular structure of proteins. Every protein is made in a similar way. The first step, also known as transcription takes place in the cell nucleus and means the Reading and copying the blueprint from the DNA – our genetic material.
Then a transport of this transcribed information out of the cell nucleus takes place, as well as a translation (Translation). This means that DNA language translated into protein language is assembled, i.e. the protein is assembled based on the DNA blueprint. A protein is then primarily a long linear chain of amino acids, similar to a string of pearls. This loose sequence of amino acids is called primary structure.
So that the proteins in primary structure can now start their work, they still have to folded This is a very complex process. First, the protein chain can be twisted, for example, creating a spiral, which, due to its typical shape, alpha-helix. This form is the most common secondary structureThrough further folding steps, the proteins achieve a three-dimensional shape – the tertiary structureIn this state they combine and work together with other proteins.
Did you know? The first amino acid to be discovered was cystine in 1810. It took until 1953 for the amino acid sequence (primary structure) of an entire protein to be deciphered. Frederic Sanger was able to determine the amino acid sequence of insulin decrypt.
Chaperone – The chaperones of our bodies
You can see from the diagram that the amino acid sequence is not enough as a primary structure. In order for the proteins in our body to carry out their tasks, they need a few intermediate steps. Only in the tertiary structure do the amino acids form a three-dimensional structure that is functional. There is a lot of work to be done before they get there.
There must new connections are formed and sulphur-containing bridges are formed between individual amino acidsThe whole thing becomes very complex and is extremely prone to errors. One incorrect binding and the protein is no longer functional.Therefore, several quality controls in our body that are supposed to guarantee that everything is as it should be.
One of these quality controls is the chaperoneIf someone is interested in England and language, then the meaning is often already clear. A little tip: it is often used in the successful Netflix series "Bridgerton".
A chaperone is an older woman who accompanies a younger woman as a protector. A chaperone from England is then something like a decency protein. It helps new proteins to fold or broken proteins to fold correctly again.
Did you know? How many proteins are there in the world? The complexity of protein architecture is difficult to grasp. For this reason, scientists have developed an artificial intelligence that can predict the three-dimensional shape of a protein with a high degree of probability. "AlphaFold" was able to predict 215 million proteins and their tertiary structure in 2022 alone. The work of the researchers from Bael is considered one of the most important in recent years, because with the help of artificial intelligence, drugs and vaccines can be developed more quickly in the future.
Loss of proteostasis – how do misfolded proteins occur?
Between 40 and 80% of all proteins are misfolded and need help. That is a huge number. There are several factors that can have a negative impact on protein structure. These include Ultraviolet radiation, heavy metals, heat or ethanolEspecially with food or dietary supplements It is therefore important to pay attention to appropriate certificates.
This environmental influences affect our proteins as well as our DNA. In addition, oxidative stress – colloquially an excess of free radicals – to the protein balance. And if that wasn’t enough, there is also the ER stress.
ER stands for endoplasmic reticulum, a facility in each of our cells whose function could be described as a logistics center. This logistics center can become overloaded due to high demand and goods can no longer be delivered correctly. What would cause a lot of trouble for Amazon, Alibaba and co. is also dangerous for the cell. All of the above influences can unfold proteins and thus render them useless.
Proteostasis – how the body defends itself
Proteostasis involves several mechanisms in an effort to maintain balance. For the sake of clarity, we will focus on two of the most important mechanisms. In response to harmful environmental influences, the cell produces increased amounts of proteins from the heat shock familyThese are very resilient proteins that can stabilize other proteins in situations of cellular stress. They do this in conjunction with chaperones.
If stabilization or restoration of correct folding is not successful, the proteins are initially unusable and must be disposed of.What the waste incineration plant or the recycling center does for us, the body does for us proteasomeTogether with a small protein called ubiquitin (Ub) the broken molecule is marked several times, degraded and broken down into the individual amino acids.
All these systems work in a coordinated manner to restore or dispose of misfolded proteinsThis enables the body to prevent the accumulation of damaged components and to ensure the continuous renewal of intracellular proteins. Another component of our cellular waste disposal is the autophagy, which we present to you as the 12th Hallmark of Aging.
So much for the theory. In practice, unfortunately, there is no guarantee that these sophisticated mechanisms will work at all times. The keyword time brings us to the next point.
Did you know? There are different heat shock proteins in our body. They are classified according to their weight. As their name suggests, they are activated by heat, among other thingsOne of the best ways to do this is infrared cabins or sauna sessions. An increase in the concentration of heat shock proteins is associated with a number of health benefits.
In a study, the researchers were able to show that higher levels of Hsp70 could reduce the inflammatory mediator interleukin-10This explains why the researchers believe that sauna inflammations how to help arthritis.
Wrinkles – top for proteins, flop for old age
While we think of wrinkles as a sign of age and therefore as having a negative connotation, we now know that the opposite is true for proteins.
Many studies have shown that proteostasis changes with age. chronic accumulation of misfolded or unfolded proteins contributes to the development of some age-related diseases such as Alzheimer's disease, Parkinson's disease and cataracts. The frequency of these pathologies is constantly increasing due to increasing life expectancy.
The Generation of chaperones in response to stress is also significantly reduced in old ageStudies on animal models support the hypothesis that the decrease in chaperones is the cause of a reduced lifespan. For example, genetically modified worms and flies, which produce increased amounts of chaperones, are particularly long-lived. An upregulation of some heat shock proteins was also found in long-lived mouse strains.
In addition, studies on mammalian cells show that upregulation of SIRT1 improves the heat shock response. SIRT1 belongs to the gene family of sirtuins, which due to the numerous effects associated with ageing is considered longevity pathways Many other experiments and studies have provided scientific evidence for the connection between chaperone levels and lifespan – but listing them all would go beyond the scope of this article.
Proteostop
Medical-biological research has already done a lot of educational work with regard to proteostasis, but are there any concrete approaches to stopping the age-related weakening of proteostasis? In fact, there are many studies on this.
One approach aims to activate chaperone-mediated protein stability and foldingIn a mouse model, drug-induced induction of a specific heat shock protein preserved muscle function and slowed the progression of certain muscle diseases. In other model organisms, researchers also used chaperones and thereby improved age-related phenotypes. The chaperones of our bodies are not only gentlewomen, but also fighters on the front line against aging.
Another approach is the proteasome and other mechanisms that serve to break down damaged proteins, as studies show that the activity of these systems decreases with age. This was achieved using selected enzymes that have exerted their effect within this complex signaling pathway.
A dietary supplement with spermidine activated the autophagy systemThis refers to the degradation of damaged cell structures (such as proteins). In simple terms, autophagy is similar in its function to the proteasome we know.
Wrinkles – top for proteins, flop for old age
While we think of wrinkles as a sign of age and therefore as having a negative connotation, we now know that the opposite is true for proteins.
Many studies have shown that proteostasis changes with age. chronic accumulation of misfolded or unfolded proteins contributes to the development of some age-related diseases such as Alzheimer's disease, Parkinson's disease and cataracts. The frequency of these pathologies is constantly increasing due to increasing life expectancy.
The Generation of chaperones in response to stress is also significantly reduced in old ageStudies on animal models support the hypothesis that the decrease in chaperones is the cause of a reduced lifespan. For example, genetically modified worms and flies, which produce increased amounts of chaperones, are particularly long-lived. An upregulation of some heat shock proteins was also found in long-lived mouse strains.
In addition, studies on mammalian cells show that upregulation of SIRT1 improves the heat shock response. SIRT1 belongs to the gene family of Sirtuins, which are considered to be the most important antioxidants due to their numerous effects related to aging. longevity pathways Many other experiments and studies have provided scientific evidence for the connection between chaperone levels and lifespan – but listing them all would go beyond the scope of this article.
Proteostop
Medical-biological research has already done a lot of educational work with regard to proteostasis, but are there any concrete approaches to stopping the age-related weakening of proteostasis? In fact, there are many studies on this.
One approach aims to activate chaperone-mediated protein stability and foldingIn a mouse model, drug-induced induction of a specific heat shock protein preserved muscle function and slowed the progression of certain muscle diseases. In other model organisms, researchers also used chaperones and thereby improved age-related phenotypes. The chaperones of our bodies are not only gentlewomen, but also fighters on the front line against aging.
Another approach is the proteasome and other mechanisms that serve to break down damaged proteins, as studies show that the activity of these systems decreases with age. This was achieved using selected enzymes that have exerted their effect within this complex signaling pathway.
A dietary supplement with spermidine activated the autophagy systemThis refers to the degradation of damaged cell structures (such as proteins). In simple terms, autophagy is similar in its function to the proteasome we know.
