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What is stem cell exhaustion, and how does it affect aging?

We all recognize the signs of aging as they appear. Everything from wrinkles and thinning hair to age-related diseases such as Alzheimer’s and cancer. But how we age is different for each of us. Some people will still look young and healthy well into old age, while others age much faster than their years. Understanding what processes are at work to cause these differences could help us stop the clock on aging. One of the key changes our bodies undergo, which might hold the key to aging, is stem cell exhaustion.

What are stem cells?

human body cells

Stem cells are about the most important cells in our bodies. Unlike other cells that have specific functions, stem cells can become almost anything. They help support our bodies by producing more of the cells we need, when we need them. They help fight infections, heal wounds, and recover from diseases. They are vital to keeping our bodies healthy and functioning properly.

While stem cells are miraculous, they’re not immortal. They can suffer from the same damage and aging factors as other cells. Telomere attrition, mitochondrial dysfunction, genome instability, and epigenetic alterations all affect stem cells. Eventually this damage becomes too much for our cells to function. When stem cells slow down or die, that’s known as stem cell exhaustion.

Because our stem cells are so vital, any damage to them is felt throughout our bodies. Stem cell exhaustion is therefore associated with many age-related conditions. A study on “Adult stem cells and diseases of aging” lists some of these conditions, including metabolic syndrome and diabetes, atherosclerosis, neurodegenerative diseases, osteoporosis, and cancer.

Stem cells as treatment for diseases

iv bag medical stem cell treatment

You might have heard about stem cell therapy, which is used to treat all kinds of diseases. Also known as regenerative medicine, stem cell therapy works by replacing damaged or diseased cells. Because stem cells can become almost any other type of cell, they can heal damage in all kinds of tissues in our bodies. Stem cells can be used to replace damaged heart cells in heart disease patients, for example, or replace white blood cells in people with compromised immune systems.

Bone marrow transplants are a form of stem cell therapy. Our bodies make new stem cells in our bone marrow, and these can be transplanted into other people to help heal their bodies. Bone marrow transplants are effective at supporting the immune systems of people with certain cancers and blood disorders.

There are other sources of stem cells now available to us, that open the door to even more treatments becoming available in the future. An important early source of stem cells was embryos. While this science is controversial, the embryos in question are fertilized in vitro and donated for this research. Therefore the embryonic stem cells used in science only come from blastocysts, eggs that are 3-5 days post-fertilization. At that point they have around 150 cells each.

These stem cells are more adaptable than those harvested from adult donors, but a recent development in stem cell science has reduced the need to use embryonic stem cells. In 2007 Shinya Yamanaka, a Japanese researcher, discovered a way to turn adult cells back into stem cells. This means your cells could one day be harvested from your arm or leg, turned into stem cells, and reinjected to cure your heart disease or grow you a new liver. The possibilities for this science are almost endless, and incredibly exciting.

How does stem cell exhaustion happen?

human dna

Researchers are still learning about how stem cells function, and all the amazing things they can do. As far as scientists can tell, there is no single cause of stem cell exhaustion. Instead, it’s likely a combination of cumulative factors, including exposure to Reactive Oxygen Species (ROS), inflammation, and signalling caused by cellular senescence in other parts of the body.

ROS are a type of unstable molecule that are created through metabolic processes. Getting energy from food requires a lot of complex chemical reactions at a cellular level, and they create ROS as byproducts. ROS are bad for our cells because they contain unpaired electrons. These molecules will “steal” electrons from elsewhere in our bodies (like our DNA) in order to correct the imbalance. This can cause cascading damage throughout our bodies if they destabilize too many cells.

Cellular senescence also causes a lot of damage to our stem cells, and to our bodies as a whole. Senescence is the state where a cell stops replicating. It isn’t dead, but it isn’t fully alive either. These “zombie cells” love to infect other cells around them. They send out signals telling surrounding cells to also enter senescence. This can lead to widespread, low level inflammation, and is the cause of many signs of premature aging, such as wrinkles.

The fact that stem cells are affected by the long-term buildup of damage in our bodies suggests that stem cell exhaustion is intrinsically linked to time. The more time passes, the more damage accumulates. And as that damage accumulates, it creates the effects we associate with getting older, such as wrinkles, thin skin, and degenerative diseases. There is therefore a cause and effect relationship between stem cell exhaustion and the aging process.

Our stem cells might be even more susceptible to this damage than our other cells because they tend to last much longer. For a long time, scientists thought that stem cells were immortal. They are able to self-renew, and some have been shown to survive far longer than the natural life of the individual who made them. However more extensive studies in recent years have shown that stem cells do eventually die, just a lot slower than most of our other cells.

Preventing stem cell exhaustion

Because stem cells are so useful to our bodies, and can heal so many diseases, it’s tempting to want to keep them switched on all the time so we can stay young and healthy forever. However stem cell exhaustion does play an important role in protecting our bodies from the effects of a lifetime of cumulative damage.

Our bodies are designed with many checks and balances in place to fix things when they go wrong. One study on “Immune surveillance by T-cells” showed that our immune systems monitor our cells for dangerous mutations and stop them from developing into diseases, preventing us from getting cancer several times each day! Cellular senescence stops a mutated cell from replicating, and cell death (“apoptosis”) removes damaged cells before they do us harm.

Stem cells play an important role in this process. The same DNA damage that ultimately leads to cancerous mutations is also likely responsible for stem cell exhaustion. Therefore many scientists believe that stem cell exhaustion is critical to preventing cancer. As one researcher put it, “aging may be the unfortunate mark of successful cancer suppression.

This explains the statistics around old age and cancers. According to a study on “Age and cancer risk,” the likelihood of the average American ever being diagnosed with cancer in their lifetimes is around 41%. However that risk does fluctuate with age — as an infant, the risk is 41.24%. When we reach 30, the risk peaks at 41.74%. However by the time we are 80, the chances of ever receiving a cancer diagnosis have almost halved, to 21.23%.

risk of american lifetime cancer diagnosis

Source: "Age and Cancer Risk"

While we can explain some of that drop by the limited time remaining to an 80 year old, vs. a 30 year old, if cancer is an age-related disease then we should expect the likelihood of a diagnosis to increase as we get older. The fact that the risk of developing cancer falls after we turn 40 suggests other factors are also in play. It suggests that the aging process itself suppresses the formation of cancer. And that means stem cell exhaustion isn’t just inevitable, it’s critical.

Our stem cells don’t just affect how we age, but perhaps even our ability to survive long enough to do so.

Growing old gracefully

old lady younger woman two generations

So how do we remain youthful and healthy as we age, if we can’t turn the aging process off completely? The secret lies in the cause of both stem cell exhaustion, and of harmful mutations in our other cells. The cumulative damage that our bodies collect over time is ultimately responsible both for premature cellular senescence, cell death, and harmful mutations, and for stem cell exhaustion and its associated signs of aging. Simply put, the healthier we can keep all of our cells, the longer we can defer stem cell exhaustion.

The good news is, keeping our bodies healthy doesn’t have to be difficult. Try to eat a varied, balanced diet of fruits, vegetables, nuts, and seeds. A good tip is to “eat the rainbow” — no, not Skittles, but eat fresh foods in many different colors. Different colors of fruit and veg are a good indication of different vitamins and minerals. The more you eat, the wider the range of important nutrients you get from your food.

Your diet is also an important source of antioxidants. These molecules can neutralize ROS, helping to avoid DNA damage and keeping your cells healthier for longer. Avoid eating fried or high fat foods, because they can trigger your metabolism to generate more ROS. And remember to exercise regularly, wear sunscreen, and avoid tobacco smoke in order to protect your cells to the fullest.

Our stem cells are amazing, but they need our support in order to keep us healthy and delay the signs of aging. By leading a healthy lifestyle, you can make a huge change to your cellular health that will show on your skin for years to come.

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