Stem cells are cells which show little to no differentiationIf we translate this somewhat dry, scientific formulation, we recognize the potential of stem cells. New cells can form from stem cells, from skin to muscle to liver cells. They are like a Swiss Army knife, equipped with everything a new cell needs. And that is what makes them so unique in the body. Another analogy would be the joker card in a game. You can always use this one.
Stem cells and their potential have been known in medicine for a long time. They have already been used successfully in some diseases, such as leukemia. In this article, we will also show you that there are different types of stem cells. As we age, it seems that stem cells can no longer work as effectively as before, which is why stem cell exhaustion has been included as one of the hallmarks of aging. We show you the background, explain what stem cell niches are and why there is "stem cell tourism".
Stem cells – less is not more
The decline in the ability of tissues to recover is one of the most obvious signs of aging. Let us look at the blood formation (hematopoiesis), which decreases with age. This leads to a lower production of immune cells that can adapt to the ever-changing threats. Experts use a term we are familiar with to describe this phenomenon: immunosenescence. As a result, anemia or malignant diseases of the bone marrow come.
Researchers observed this functional "stem cell wear" in mice in more or less all places in the body where stem cells are found. These include, for example, the forebrain, bones or muscle fibers. In all of these places, 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 cells. This is due to the accumulation of DNA damage (see genomic instability) and with the inhibition of the cell cycle (see cellular senescence) through the already known protein p16INK4a together. The shortening of telomeres (see telomere attrition) is also an important cause. However, these are just examples of a much larger picture of what causes functional decline in the stem cell population.
Do we simply have too few stem cells as we age?
The obvious conclusion from the results of the studies should 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 of all, you need to know that there are stem cells of varying potency exist.The most potent stem cell is the one from which we all originated: The zygote (short note: A zygote is the fusion of an egg cell with a sperm cell)
In our adult body, 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 the new cells mature. But our organs, such as the liver, lungs or intestines, also have stem cell niches. It is precisely these stem cell niches that seem to be particularly affected in old age.
Stem cell niches – the site of aging
Let's take the skin as an example. When you're young, you have a large depot of functional stem cells in the niche. These ensure that your skin renews itself quickly. These stem cell niches play a special role, especially in the case of injuries. However, not all stem cells in this niche are the same. Some are particularly hardworking and contribute particularly to cell renewal, while others are rather sluggish and contribute little to wound healing.
What happens now as we age? It seems as if the total number of stem cells does not change muchHowever, the particularly hardworking ones are increasingly missing, so that the performance of the stem cells in their niche is declining. Stem cells can also fall into a kind of senescence in which they can hardly be activated.
Under the microscope it looks as if there are enough stem cells, but in reality they are exhausted and can no longer keep up with production. The result: When we injure ourselves as we get older, there are fewer hardworking stem cells and the wound takes much longer to heal.
Too few stem cells – the obvious solution is too simplistic
So we have our solution. We need more functional stem cells so that we can renew our bodies. Unfortunately, it's not quite that simple. Excessive stem cell activity has been associated with faster agingThis finding was convincingly demonstrated in an experiment with intestinal stem cells from fruit flies (Drosophila). Increased division of stem cells resulted in premature aging.
And when cells divide uncontrollably, we have another name for it: cancer
Let us remember again INK4a (see cellular senescence) and IGF-1 (see deregulated nutrient measurement). For both parameters, a paradoxical effect has been described over the course of life. Increase in INK4a drives cells into cell cycle arrest – senescence occurs. Also, Decrease in serum IGF-1 associated with a decline in cell division abilityBoth processes occur during normal aging, but they happen with positive intentions. They reflect our body's attempt to maintain the integrity of the stem cells.
Did you know? In the Hallmarks of Aging There is often a mention of free oxygen radicals.The so-called ROS play a dual role. young age they can be beneficial to us, while an excess of ROS can destroy our DNA and proteins. ROS also affect stem cells. Too much of these radicals can potentially contribute to stem cell exhaustion.
Our body tries to do this mainly through formation of glutathione If you want to know more about it, please have a look at our article about GlyNAC We will also explain to you why it is better not to substitute glutathione and what the amino acid Glycine has to do with the topic.
GlyNAC is a promising molecule when it comes to cellular energy and biological age.
FGF2 – a new target for exhausted stem cells
In the search for ways to reactivate stem cells to our advantage, research has turned to the protein FGF2 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 limitation of their ability to recover.
The good news is that suppressing this pathway prevents this condition, making it a potential therapeutic strategy to combat stem cell exhaustion.
How can we strengthen stem cells?
Let's now move away from basic research and take a look into the future. We now know that our stem cells are less efficient as we age. But where does this come from? What causes our stem cells to age?
A possible explanation is provided by a somewhat bizarre experiment, which we already 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 were significantly rejuvenated.
These results can also be reproduced when old mice are injected with the blood of young mice, which suggests that there was no exchange of stem cells, but rather that molecular signals exist in the blood of the young micethat 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 e.g. Bryan Johnson Self-experiment in which he has his son's blood plasma given to him). Such actions rightly raise great ethical concerns. Blood transfusions are not without risk and the “fountain of eternal youth” will certainly not be found in having young blood infusedIt will be more interesting to find out which exact signaling pathways in young blood ensure 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 rejuvenate old stem cells. sport seems to be a proven means of getting the stem cells active again. In addition improved Fast the function of intestinal and muscle stem cells in animal models.
The effect of fasting is probably due to the regulation of various signaling pathways, mainly the IGF-1 and the mTOR pathway. It has also been shown that Fasting mimetics, which act precisely via this molecular axis, also have positive effects on stem cells.
Drug-induced manipulation of stem cells
Finally, possible 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 influencing the proteostasis and about the Measurement of energy signals. Based on these two mechanisms, studies have shown that Stem cell function in the skin, the hematopoietic system and the intestine can be improved.
These findings highlight once again the difficult task of unravelling the molecular basis for the anti-aging activity of rapamycin and the interconnectedness of the hallmarks of aging.
In addition to rapamycin, there is also pharmacological inhibition of CDC42 worth mentioning. Human cells in the senescence stage could be rejuvenatedOverexpression of CDC42, which is involved in the control of the cell cycle, has also been detected in a certain type of lung cancer.
Stem cell therapy – beware of false promises
As we have seen, stem cells are potent helpers in the fight against aging. If we can figure out how to restore this natural resource to its full potential, many new possibilities will be open to us.
It is precisely this hope that (unfortunately) has some black sheep who want to make a lot of money out of it. In some regions of the world, such as the Caribbean, stem cell therapy is being advertised. From improved wound healing to cancer therapy – the promises are often big, but the reality is often soberingThe FDA, the American drug authority, has even issued an official warning about such fraud cases.
Stem cells and aging: a question of time, not means
The exhaustion of stem cells is an inherent consequence of age-related damage to cells. It is not wrongly assumed that that this process is one of the main cause of aging of our body is. After all, practically all the signs of aging that we have come to know so far lead to the stem cell exhaustion.Recent studies provide a promising foundation for the assumption that the Rejuvenation of stem cells can reverse aging at the organism level.
Are these findings a kind of basis for a time machine back to biological youth? Even if the idea is appealing to some, there is currently too little evidence for this. In any case, compared to the other Hallmarks in the field of stem cell research, massive investments made.
Stem cell therapies have been ubiquitous for years and have led to drastic improvements in the treatment of diseases such as leukemia. Stem cells are also considered to have enormous potential in the field of transplant medicine.
It is therefore less a question of means than a question of timeuntil the results of stem cell research are applied to the topic of anti-aging and health span. Perhaps in the future we will no longer have to worry about how to "restore" if we can also "preserve".
The next article in this series is about the ninth hallmark of aging: Altered intercellular communication.
