Stem cells are cells, which show little to no differentiationIf we translate this somewhat dry, scientific formulation, we recognize the potential of stem cells. Stem cells can form new cells, from skin and muscle cells to liver cells.They're like a Swiss Army knife, equipped with everything a new cell needs. And that's what makes them so unique in the body. Another analogy would be the joker card in a game. You can always use it.
Stem cells and their potential have been known in medicine for some time. They are already being used successfully to treat some diseases, such as leukemia. In this article, we will also show you that there are different types of stem cells. It seems that as we age, stem cells are no longer able to work as effectively. As before, this is why stem cell depletion has been included as one of the hallmarks of aging. We'll show you the background, explain what stem cell niches are, and why "stem cell tourism" exists.
Stem cells – less is not more
The decline in tissue regenerative capacity is one of the most obvious characteristics of aging. Let's look at the Blood formation (Hematopoiesis), which decreases with age. This leads to a reduced production of immune cells that can adapt to ever-new threats. The scientific community uses a familiar term to describe this phenomenon: ImmunosenescenceAs a consequence, this can lead to... Anemia or malignant diseases of the bone marrow come.
Researchers observed this functional "stem cell abrasion" in mice at virtually all locations in the body where stem cells reside. These include, for example, the forebrain, bones, and muscle fibers. In all these locations, old or dead cells can no longer be adequately replaced by new cells.
Studies conducted on aged mice provided further insights in this direction. There, scientists recorded a Decrease in cell cycle activity in hematopoietic stem cellsThat's related to the Accumulation of DNA damage (see genomic instability) and with the Inhibition of the cell cycle (see cellular senescence) through what we already know Protein p16INK4a together. The Telomere shortening (see Telomere abrasionThis is also an important cause. However, all of these are just examples of a much larger picture of what causes a functional decline in the stem cell population.
Do we simply have too few stem cells as we age?
The obvious conclusion to be drawn from the study results would therefore be: the number of stem cells decreases with age. But is that actually true?
Not quite. If you take a closer look at stem cells, the picture becomes a little more complicated. First, you need to know that... There are stem cells of varying potency.The most potent stem cell is probably the one from which we all originated: the zygote (brief note: A zygote is the result of the fusion of an egg cell and a sperm cell)
In our adult bodies, stem cells are organized somewhat differently. mostly in the form of so-called stem cell niches.These are located in different places, depending on where they are needed. Our skin has several stem cell niches, as this is where new cells mature. But our organs, such as the liver, lungs, and intestines, also have stem cell niches. These stem cell niches appear to be particularly affected in old age..
Stem cell niches – the site of aging
Let's take skin as an example. In your youth, you have a large reservoir of functional stem cells in the niche. These ensure that your skin regenerates quickly. These stem cell niches play a particularly important role in the case of injuries. However, not all stem cells in this niche are the same. Some are particularly industrious and contribute significantly to cell renewal, while others are rather sluggish and contribute little to wound healing..
What happens in old age? It seems as if the total number of stem cells has not changed significantlyHowever, the most active stem cells are increasingly lacking, so their performance in their niche declines. Stem cells can also enter a state of senescence in which they are barely activatable.
Under the microscope, it looks as if there are enough stem cells present, but in reality, they are depleted. and can no longer keep up with production. The result: If we injure ourselves in old age, fewer efficient stem cells are available and wound healing takes significantly longer.
Too few stem cells – the obvious solution is too simplistic.
So we have our solution. We need more functional stem cells so we can regenerate our bodies. Unfortunately, it's not quite that simple. Excessive stem cell activity has been associated with faster aging.This finding was convincingly demonstrated in an experiment with intestinal stem cells from fruit flies (Drosophila). Increased stem cell division resulted in premature aging.
And when cells divide uncontrollably, we have another name for it: cancer.
Let's remember... INK4a (see cellular senescence) and IGF-1 (see deregulated nutrient measurementFor both parameters, a paradoxical effect has been described over the course of a lifetime. An increase in INK4a causes cells to enter a cell cycle standstill. – senescence occurs. Also, a A decrease in serum IGF-1 is associated with a decline in cell division capacity.Both processes occur during normal aging, but happen with a positive intention. Specifically, they reflect our body's attempt to maintain the integrity of stem cells.
Did you know? In the Hallmarks of Aging The term "free oxygen radicals" is frequently used. These so-called ROS play a dual role in this context. At a young age, they can be an advantage for usWhile an excess of ROS can damage our DNA and proteins, ROS also affect stem cells. An excess of these radicals can potentially contribute to stem cell depletion..
Our body mainly tries to do this through the Glutathione formation to prevent.If you want to know more, then feel free to check out our article about GlyNAC In there we'll also explain why it's better not to substitute glutathione and what the amino acid is. Glycine related to the topic.
GlyNAC is a promising molecule when it comes to cellular energy and biological age.
FGF2 – a new target for depleted stem cells
In the search for ways to reactivate stem cells to our advantage, research has focused on the protein FGF2 employed. This is a Growth factor for connective tissue cellsIf the FGF2 level in the body is high, this leads to exhaustion in aged stem cells and thus to a restriction of their ability to recover.
The good news is that suppressing this signaling pathway prevents this condition. This therefore represents a potential therapeutic strategy for combating stem cell depletion.
How can we strengthen stem cells?
Let's now move away from basic research and take a look at the future. We now know that our stem cells become less efficient with age. But what causes this? What makes our stem cells age?
One possible explanation comes from a somewhat bizarre experiment, which we also discussed in the 5th Hallmark of Aging. If you sew two mice together, one young and healthy, the other old and sick, you get a so-called ParabiosisInterestingly, the researchers found that in the old mice, the stem cells in the cell niches of the brain and liver had significantly rejuvenated.
These results can also be reproduced by injecting old mice with the blood of young mice, suggesting that it There was no exchange of stem cells, but rather that molecular signals exist in the blood of the young mice., which make the stem cells younger again. Which ones, that remains the question.
Did you know? Such parabiosis experiments always cause a great stir in the press (see z.B. Bryan Johnson (Self-experiment, in which he receives blood plasma from his son). Such actions rightly raise serious ethical concerns. Blood transfusions are not without risk, and the "fountain of youth" will certainly not be found in having young blood infused into oneself.It will be more interesting to find out which precise signaling pathways in young blood are responsible for the renewal of stem cells. This could then lead to the development of new therapeutic methods in the future.
Aren't there other ways?
Fortunately, young blood is not the only thing that can be used to revive old stem cells. sport This appears to be a proven method for reactivating stem cells. Furthermore improved Fast the function of intestinal and muscle stem cells in an animal model.
The effect of fasting is likely due to the regulation of various signaling pathways, primarily the IGF-1 and the mTOR pathway.This also made it possible to show that Fasting mimetics, which act precisely via this molecular axis, also have positive effects on stem cells.
Drug-induced manipulation of stem cells
Finally, potential drug interventions to improve stem cell function were also on the research agenda. Scientists were particularly interested in the... mTOR inhibitors Rapamycin – an old acquaintance. This molecule exerts its effect via the Influence of the Proteostasis and about the Measurement of energy signals. Based on these two mechanisms, studies have shown that Stem cell function in the skin, blood-forming system, and intestines can be improved..
These findings highlight once again the difficult undertaking of unraveling the molecular basis for the anti-aging activity of rapamycin. Furthermore, they underscore how interconnected the markers of aging are.
Besides rapamycin, there is also the pharmacological Inhibition of CDC42 Worth mentioning. This allowed human cells in the senescent stage to be rejuvenated.. Overexpression of CDC42, which is involved in the control of the cell cycle, among other things, has also been detected in a specific type of lung cancer.
Stem cell therapy – beware of false promises
As we have seen, stem cells are powerful allies in the fight against aging. If we can find out how to restore this natural resource to its full strength, many new possibilities will open up for us.
Unfortunately, some unscrupulous individuals exploit this very hope to make a lot of money. In some regions of the world, z.BIn the Caribbean, stem cell therapy is being advertised. From improved wound healing to cancer therapy – The promises are often grand, but the reality is often sobering.The FDA, the American drug regulatory agency, has even issued an official warning about such fraudulent schemes.
Stem cells and aging: a question of time, not resources
Stem cell depletion is an inherent consequence of age-related damage to cells. It is rightly assumed that... that this process is one of the Main causes of aging of our bodies isUltimately, virtually all the signs of aging that we have encountered so far culminate in the Stem cell depletionRecent studies provide a promising foundation for the assumption that the Stem cell rejuvenation can reverse aging at the organismal level..
Do these findings provide a kind of basis for a time machine back to biological youth? While the idea may be appealing to some, there is currently too little evidence to support it. In any case, compared to other hallmarks in the field of stem cell research, massive investments done.
Stem cell therapies have been ubiquitous for years and have led to drastic improvements in the treatment of diseases such as leukemia.Furthermore, stem cells are recognized as having enormous potential in the field of transplantation medicine.
It is therefore less a question of resources than a question of time....until the results of stem cell research are applied to the topics of anti-aging and healthspan. Perhaps in the future we won't even have to worry about how to "restore" if we can also "maintain."
The next article in this series will discuss the ninth sign of aging: Altered intercellular communication.
