The genome is a term that, in simple terms, denotes the entirety of an individual's heritable information . This is information for the production of proteins, which can influence and change the appearance of the body in a variety of ways. You can think of DNA a bit like the code plan of a computer program. The information stored on the DNA is translated into amino acids by special helpers, from which the proteins in our body are ultimately created. We'll spare you the details; that would be a little too much biochemistry all at once.
Every day, millions of cells in our body divide, which means that the genetic information also has to be copied. This means that each cell has a copy of around 3 billion so-called base pairs and ideally in the correct order. It almost goes without saying that something can go wrong. Our body is equipped with a whole range of helpers that can correct errors in the copying process. These helpers are also used in the event of damage from “outside”.
When you're young, this highly complex system (mostly) works perfectly, but as you get older, more and more errors creep in. The so-called genomic instability is one of the Hallmarks of Aging. These Hallmarks are an attempt to explain the aging process scientifically and at a molecular level. Here we will introduce you to the first Hallmark in more detail and explore the question of why people age.
If too much DNA damage accumulates (for example due to genomic instability), the cell dies or degenerates.
Genomic instability – the danger from outside
Threats of external origin include chemical or biological agents and thus, for example, medications. In addition, physics can also damage DNA via UV light, in particular UV-C light.
If you've ever gotten sunburned, then you know what we're talking about. The UV light penetrates our skin and can break off entire pieces when it hits the DNA. If the UV radiation is low or we have applied sunscreen, the damage is small and our body can repair it.
In the other case, the DNA is damaged to such an extent that the cell is no longer functional. She dies. If this happens to a large extent, we see it as reddening of the skin or, even more impressively, in the form of blistering. In the long term, this UV damage can be very damaging to the skin and lead to “skin cancer”.
Fortunately, the worst doesn't always have to happen, but long-term high UV exposure without protection also ages the skin. In particular the structural molecule collagen is gradually destroyed by sunlight.
Did you know? With around 30%, Collagen is the most common protein in our body. It is found in the skin, bones and tendons. UV radiation can destroy collagen in two ways. On the one hand, the work of the fibroblasts (these cells form collagen) is inhibited and, on the other hand, UV radiation activates so-called collagenases, which “eat” functional collagen. The good news is that we can also supply collagen from the outside in the form of collagen peptides and thus support our skin.
Collagen peptides (also known as collagen hydrolyzate) are a scientifically recognized method for increasing collagen levels in cells.
Genomic instability from within
Let's move on to the threats of endogenous origin. During cell division, two daughter cells are created from one cell. Naturally, both daughter cells must receive the same genetic information so that they can develop according to their intended purpose. To do this, the DNA doubles during cell division (replication) and then divides evenly between the two new cells that are created. This sometimes results in so-called DNA replication errors, for example incorrect pairings between the two strands. This is suboptimal, but the body is prepared for it.
Cell division is organized as a cycle and control stations are built into this cycle. If an error is discovered, cell division stops and, in the best case, the error is repaired. In the event that the repair system cannot repair the damage, the cell is put into the state of senescence .
We'll talk about senescence later, but to give you a better picture: this cell has just been put into “zombie mode”. She is neither alive nor really dead.
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Free radicals and reactive oxygen species – what do they have to do with aging?
Free radicals and reactive oxygen species sound a bit like explosive biochemistry. And that's it. Especially in energy-intensive metabolic processes in the body, e.g.b In the mitochondria, free radicals may arise. These are particularly reactive molecules that disrupt the reaction balance and can therefore hinder reactions that are useful to the body.
If this is an oxygen molecule, these molecules are referred to in technical jargon as reactive oxygen species. The body also has an answer to this, because antioxidants can neutralize these troublemakers to a certain extent. The body's most important antioxidant is glutathione, which we explained to you in our article about GlyNAC .
There is even a theory of aging that relates almost exclusively to free radicals. In short, long-term exposure to these reactive molecules is said to age us. This theory is now a little outdated, as we now know that a certain level of free radicals can be beneficial for the body. Only when the balance is tipped do free radicals pose a threat to our genomic stability.
Genomic instability & nuclear envelope defects
The damage mentioned, regardless of whether it is of external or internal origin, is one of the direct lesions of our blueprint, the DNA. In addition, defects in nuclear architecture can also cause genome instability. This works as follows.
The cell nucleus is a separate space surrounded by a shell and the place in the cell where the DNA is located. The shell of the cell nucleus is made up of many different proteins, including proteins from the lamin family. “Lamina” is Latin and means plate, disk or layer. These “layer proteins” must be formed correctly for the shell to function properly.
It behaves here in a similar way to a house roof, which must be neither too rigid nor too soft in order to distribute the loads as best as possible. If a problem occurs in connection with these “layer proteins” of the nuclear envelope, the genome becomes unstable. The reason for this is the fact that DNA is connected to the nuclear envelope via molecules.
Let's look at a real example. There are people who can only form a shortened form of a special lamin. The truncated protein is called progerin . Accordingly, the disease is referred to as Progeria (=accelerated aging). In these people the nuclear envelope is not sufficiently stable. The result is a five to tenfold increase in aging speed. Those affected often die in childhood or adolescence.
Did you know? Researchers at the Technical University of Munich have taken a closer look at the clinical picture of progeria and made an exciting discovery. Faulty progerin also occurs in normal cells. However, in people with progeria, around 20 times more progerin is produced, so that the cells' waste bins become clogged. The autophagy, also one of the hallmarks of aging, no longer works in these people either.
The second exciting discovery of the study was that the administration of sulforaphane, a secondary plant substance from broccoli, increased autophagy could and the “garbage bin of the cells” (proteasomes) worked better again.
If the nuclear envelope is damaged or unstable, cell health is significantly impaired. Genomic instability is one cause of this.
Genomic instability in the future
Even though progeria is an extremely rare disease, with a frequency of 1:1 million, the underlying defect is also relevant to each and every one of us. Scientists have proven that people with normal aging also produce progerin, which disrupts the nuclear architecture.
The genome is therefore constantly unstable due to various influences, whether from outside or from within. No one is exempt from this. The good news is that our bodies are prepared for many of these challenges. However, efforts to keep instability at bay are working. repairs become less than ideal as we get older.
The question of why some people age more slowly can probably be answered by the fact that these people have good repair mechanisms to limit genomic instability. Recent publications on the topic not only deepen our knowledge, but also show possible ways in which we can keep genomic instability in check.
The next article in this series will focus on the second hallmark of aging: Telomere attrition.
