The End of Aging: IPS Cells
I don’t know you and you don’t know me, but I bet there’s one thing that we both have in common: we’re all getting older. And whether we like it or not, time never stops. Aging has always been inevitable, but it doesn’t have to be. With new advances in stem cell therapies, the future of human longevity is near.
What is Longevity and What Does it Entail?
First of all, it’s important to acknowledge that human longevity does not necessarily mean living forever. The end of biological aging does not mean the end of death. Because, it’s not about living forever, it’s about extending our lifespans to be able to enjoy life longer.
For most, a lifespan is perceived to be just how long you live. However, this common way of looking at time is insufficient. A lifespan is much more of a measurement of existence rather than living. To understand this concept, let’s put life into perspective:
The average global life expectancy is around 73 years old. To break it down, on average 21 years of your life are spent growing up and going to school. The next 45 years are spent raising a family and working a day job. Let’s say you retire in your 60s. That gives most people 15 years to do whatever they want. But, more than half of adults over the age of 65 face health issues that don’t allow them to live their lives to the fullest. At that point you’re just existing, not living.
So, we can see that living longer is pointless if you spend most of your free years combatting illness and health problems. The goal of human longevity is to enable not only a longer lifespan, but also a healthier one. Meaning, that in conjunction with a lifespan, what’s really at stake here is your health-span.
Aging:
The modern-day human race constantly tries to stay young, both mentally and physically. We stress the importance of eating healthy and exercising, and we as a society buy into all of those “anti-aging” beauty products. Essentially, all we want is to stay young forever. The key word here is “young.” Living longer isn’t the problem, aging is.
You may be surprised to hear that we have already increased our life expectancy. A report from Our World in Data showed that a 5-year old in 1841 had a life expectancy of 55 years. Today, the same child can expect to live up to 82 years. And we can credit our increasing expected lifespan to the improvement of modern medicine, safer environments, and overall better living conditions.
But, we have not increased our health expectancy. Aging is the cause of almost all diseases, and diseases are what hinder healthy life expectancy. So, how do we stop aging? First, we need to understand why people age.
Epigenetics
As mentioned in telomeres, our DNA has protective mechanisms surrounding itself. These mechanisms are called the epigenome, which determines the expression of DNA. The epigenome determines what proteins are expressed by each cell. It’s what differentiates a heart cell from a liver cell and helps protects the body from dieseases.
Over time, cells loose the structure of their epigenome because they begin to “forget” what their epigenome structure is. This can cause specific cell types to behave like other cells, making us more sensitive to diseases, like cancer, as we age.
Think about it this way: when your skin cells start acting like blood cells then your body starts to break
How Do We Combat Aging?
There are many ways to solve the root causes of aging, just as aging is caused by many factors. Aside from natural methods, there are some new scientific developments that are reinvisioning longevity. One of which, is stem cell therapies.
Stem Cells:
Perhaps one of the most effective forms of anti aging is through stem cell rejuvination.
What are stem cells?
All cells have different functions throughout the body. Once a cell is assigned a type at a baby’s birth, it functions as it should, and cannot change to a different type of cell with a different function. However, there is one type of cell that is flexible, and has the ability to function as different types of cells based on your body’s needs. These cells are stem cells. Stem cells are able to replace damaged cells within the body and allow people to heal themselves.
If stem cells are so great, then what’s the issue?
Stem cells age as we do. The older we get, the effectiveness and amount of stem cells we have decreases exponentially. Stem cells from an embryo are much more versatile than those from an adult. Baby’s stem cells found in young children, embryos, or umbilical cords, are the most versatile because a baby’s cells are still learning what to do when a they are born. Adult stem cells, found mainly in bone marrow or fat, are somewhat different because although they can become many different types of cells, they can’t become every type.
Think of it like this: if you break your foot at 5 years old, you will fully recover. But, if you break your foot at 60, you will likely live with side effects from that injury for the rest of your life because your body’s ability to rejuvenate has decreased.
This aging process can be combatted with stem cell therapies, which replenish the supply of stem cells to allow the body to repair and rejuvenate.
Ethical IPS Cells:
Cellular reprogramming can reset the epigenetic clock in our bodies.
Early on, the youthful stem cells used in stem cell therapies were only available in the form of embryonic stem cells. These cells are pluripotent, meaning that they can grow into any type of tissue in the body (the most versatile because a baby’s cells are still learning what to do when they are conceived). However, the use of these cells came with several ethical issues and debates due to the fact that they were derived from embryos. Like the debates surrounding abortion, the use of embryonic stem cells poses similar questions. Therefore, it was not the best option for stem cell therapies. And, adult stem cells aren’t always an option due to their limited capabilities.
Embryonic stem cells (ESCs) were thought to be the only source of pluripotent cells. That was until 2006 when scientist Shinya Yamanaka managed to convert differentiated adult cells into embryonic stem cells through a process called cellar reprogramming. A cell dosed with his reprogramming factors erased the marks on the epigenome. In the process, the cell lost its identity and the erroneous marks gained through aging, restoring itself to an embryonic state. The discovery opened the door to regenerative medicine and was the first step in combatting aging-related dieases such as Alzheimers, Parkinson’s, and diabetes. Since then, many scientists have taken his discovery further to experiment with reprogramming cells in living organisms.
Like Yamanaka, scientists have discovered that genetic reprogramming can be used to program adult stem cells back to an embryonic state. These cells are called induced pluripotent stem cells, which act in the same way as young stem cells. Essentially, this tricks the cell aging process.
How does the IPS reprogramming process work?
As previously discussed, the epigenome shapes our genome, and determines what is expressed. It creates the “identity” of cells. However, the proteins making up the epigenome lose their structural abilities over time, making us very susceptible to disease and aging. Scientists can reprogram cells to renew themsevles back to their original epigenome.
In order to turn adult cells back into embryonic-like stem cells, scientists take a person’s fibroblast and use 4 proteins to activate pluripotency within the cell. They insert these reprogramming factors — Sox2, Oct4, Klf4, and cMyc — into the cell via a virus. These transcription factors bind together to form an interconnected autoregulatory circuitry, triggering their own core promoter genes along with other pluripotency associated genes. By reactivating these genes in adult cells, the cells become pluripotent, meaning they reprogram back into an embryonic state. In the end, the induced pluripotent stem cells(IPS) are identical to embryonic stem cells.
What are the benefits of IPS Cells?
- IPS cells are more ethically acceptable because they do not require the use of an embryo.
- IPS cells and embryonic stem cells are extremely similar. They can divide and produce copies of themselves indefinitely and can be used to derive any kind of specialized cell.
- Because IPS cells are pluripotent, scientists can wait for their differentiation to reoccur in order to mimic the early steps of embryonic development. This makes IPS cells a good way to study early age onset diseases
- IPS cells give researchers a way to create and study diseased cells that contain the same genetics as their patients. The reprogramming of cells from individuals in the context of their genetic background and epigenetic behavior have been shown to reflect those of the cells from the donor individual. Therefore, IPS cells are a great tool to model human diseases if reprogrammed from cells of a patient with genetic variations causing the disease. They are already in use for drug discovery.
- Personalized medicine avoids the need for a donor: IPS cells can be created from individual patients and then be transplanted back into those same patients. So, someone with Parkinson’s has the potential to be treated with stem cells derived from their own cells, eliminating the need for immunosuppressive drugs or transplants.
- IPS cells reduce the possibility of rejection of the transplanted cells by one’s own body because they were originally derived from the same body.
Downsides?
So, if IPS cells are identical to stem cells then there shouldn’t be any differences or downsides, right? Wrong.
- One major risk of using IPS cells is that the viruses used for generating the cells are associated with cancer. For example, overexpression of c-Myc, one of the genes used in the reprogramming process, can trigger the growth of cancerous tumors.
- Several studies suggest that IPS cells embryonic cells function differently. This is because the cells are never 100% reprogrammed. This is caused by incomplete reprogramming of the cells and the possible genetic changes acquired cells when they grow and multiply. But, researchers are still looking into the effects of these differences.
- Although appealing, the cost of develping affordable and effective treatments using IPS cells remains a challenge.
- More scientific research is also needed to understand just how the reprogramming process works inside of cells in order to overcome the downsides.
The Future of IPS Cells:
There have been significant recent advances in the IPS cell industry. Originally, creating IPS cells involved transcription factors that caused permanent genetic changes inside of the cell, which led to the possibility of tumours forming. Now, scientists have developed methods for producing IPS cells without this genetic modification. These new techniques are an important step towards making specialized IPS cells could be safe for use in human patients.
A recent study at the Stanford University School of Medicine set out to figure out a way to rewind the aging clock without inducing pluripotency. They found that by tightly controlling the duration of the exposure to the transcription factors, rejuvenation was promoted in multiple human cell types. They produced the cells by repeatedly exposing them to the reprogramming proteins by inducing daily RNA messages which encoded the instructions for making the proteins, into the adult cells. Over the course of two weeks, these proteins rewinded the cells’ fate back until they resembled the young, embryonic-like pluripotent cells from which they originated. During the process the cells shed memories of their previous identities, allowing them to revert to a younger state, wiping their DNA clean of the molecular tags that accumulated as they aged.
Following the experiment, scientists began to wonder whether exposing the adult cells to the reprogramming proteins for days rather than weeks could trigger this youthful reversion without inducing full-on pluripotency.
The researchers are now optimizing the reprogramming proteins and exploring the possibility of treating human cells or full tissues without removing them from the body.
Other researchers have been looking for ways to replace the trasncription factors discovered by Yamanaka. In the journal Cell Stem Cell, Harvard Stem Cell Institute faculty published their discovery of a single chemical that replaced two of the genes used in reprogramming. Their team named the chemical RepSox (yes like the Boston Red Sox), which replaced Sox2 and cMyc, the two genes associated with the formation of cancerous tumors when introduced via a virus.
In addition, further scientific research is now being done by many groups to understand how reprogramming fully works and how these cells can be produced to meet the high quality and safety requirements for clinical use in stem cell therapies. This same rejuvenation process can be applied to longevity, in which people could potentially receive stem cell treatments to revitalize their bodies back to a youthful state. So, in simple words, human longevity is on the horizon.
Is Longevity Ethical?
The ethics of human longevity are a long and complicated debate (I have another article in my portfolio that goes into this further so feel free to check it out). The creation of IPS cells has helped settle some concerns regarding the use of embryonic stem cells in longevity-related treatments. But to sum it up, let’s explore another valuable question: does human longevity decrease the value of life? I would argue that if done ethically, it does not. If we are simply trying to maximize the number of healthy years that we spend on this planet, then longevity can be regarded as a very fancy way of taking care of yourself and your health. Like I said, it’s about living, not just existing.
Takeaways:
- The goal of longevity is not only to increase our lifespans, but also our health-spans.
- Biological aging is caused by many factors, including telomere shortening, senescent cells, free radicals, and the loss of the epigenome.
- Aging can be combatted through diet and natural methods. Autophagy and increased intake of antioxidants can help decrease aging rates.
- The amount of stem cells we have and their capabilities decrease over time, limiting the body’s ability to rejuvenate itself and contributing to aging.
- Induced Pluripotent Stem Cells (IPS cells) are created by reprogramming adult stem cells back into an embryonic state using four transcription factors. These cells are essentially identical to embryonic stem cells.
- IPS cells are a more ethical alternative to embryonic stem cells and offer a possibility of personalized medicine. They also don’t require the need for donors in stem cell treatments, and therefore eliminate the possibility of rejection within the patient’s body.
- IPS cells are already being used in drug discovery and many researchers are working to find a way to make IPS cells safe for clinical use in humans.
- Although IPS cells are able to function like embryonic ones, they also come with downsides such as the formation of cancerous tumors.
- Recently, researchers at Stanford have found a way to reprogram stem cells using daily RNA messages, without the risks that come with using the viral transcription factors.
- Harvard Faculty have also discovered a chemical that can be used to replace two of the reprogramming genes associated with cancer.
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