The Future of Aging: Cellular Reprogramming and Longevity

Billionaires are investing heavily in cellular reprogramming to reverse aging and enhance human longevity.

### The Quest for Reversing Aging: Innovations, Challenges, and Future Prospects
* ⏳ A group of startups is attempting to reverse aging, with billionaires investing heavily in the hope of developing **effective technologies before it’s too late for them**.
* 🔬 Scientists are exploring cellular reprogramming, a technique that could **rejuvenate human cells** and potentially allow for the **reversal of aging within a few years**.
* 📉 Aging causes an increase in mortality risk, with **chances of dying doubling roughly every eight years** after age 30, highlighting the **urgency of finding solutions**.
* 🧬 Stem cells play a crucial role in tissue regeneration, but their efficiency **declines with age**, leading to **slower healing** and **more visible signs of aging**.
* 🎓 Shinya Yamanaka's discovery of the **"Yamanaka factors"** allows for the reprogramming of differentiated cells back to a **stem-like state**, offering **significant potential for regenerative medicine**.
* 🔄 Researchers aim to **partially reprogram cells to rejuvenate them** while retaining their specific identities, which could lead to treatments for conditions like **arthritis or age-related blindness**.
* 💰 Major investments in this field are pouring in from tech billionaires like **Jeff Bezos and Sam Altman**, with startups like **Altos Labs and Retro Biosciences** at the forefront of this research.
* ⚠ However, the journey to human applications is fraught with risks, including the **potential for cancer and other harmful side effects**, underscoring the **complexity of biological systems** compared to technological ones.

Imagine if you could turn back the clock to reverse aging. Get rid of wrinkles, gray hair, or see 20/20 again. Well, there's a handful of startups trying to do exactly that, and billionaires are pouring money into this, hoping the tech will be developed before it's too late for them. These tech billionaires, they like their lives a lot, and they just don't want to give it up, so they're driving a lot of this. Scientists are trying to manipulate human cells to rejuvenate your body. It's a technique they're calling cellular reprogramming, and it could be reality in just a couple of years. I'm unapologetically afraid of dying. If you cure aging and people have the mortality of young adults, then they would live thousands of years. Hilary: But how does this work? Should we worry about side effects? And how close are we really to cheating death?

I'm Hilary Brueck, and I'm a health correspondent here at Business Insider. João: Aging is an inevitable and progressive process of loss of viability and increase in vulnerability. So once you reach about age 30, your chance of dying doubles roughly every eight years. And you see that across populations, from poor countries to wealthy countries, it doesn't matter. That's very consistent across populations. Hilary: But to understand aging, we need to think about how it all starts. Because we start out in a much different, more flexible shape. Picture a fertilized egg, the single cell where we all begin. That cell could become anything. It's what we call a stem cell. Stem cells are versatile and can turn into any type of cell your body needs. And then, as they develop, the stem cells become more specialized. Scientists might say they're differentiated cells, but really it's kind of like they're getting job titles,

like a skin cell, or a brain cell, or a hair cell. Our stem cells are like our body's built-in rejuvenation system. They're constantly turning over, making new stuff for us, keeping our body going with new hair, new skin, fresh neurons. These stem cells are required for regenerating tissue because our tissue, you know, our cells die and have to be constantly replaced. That's why, you know, when you fall down and get a bruise, it quickly repairs itself. As we age, the number of these stem cells decreases and their efficiency declines, so our body has a harder time repairing and replacing tissues, and this leads to slower healing and more signs of aging all over. Aging is really an accumulation of changes. A lot of it is chemical damage. And eventually, things start becoming dysfunctional. That buildup of damage over time as we age creates problems. Some scientists think of it kind of like a photocopier

or something, like where the more copies you make, the more worn out it gets, and the more little glitches and errors it has on it. This damage in our DNA is kind of like glitches in our human programming. Over time, the errors cause issues because our bodies use that code to make the proteins that sustain our whole life and fight infections and thrive as people. When the instructions for our cells are damaged, they stop working properly, which is part of what happens during aging. So when scientists talk about reprogramming, what do they mean? So this idea of reprogramming is, could we take cells that are fully differentiated, like the skin cell or muscle cell or whatever, and program them to go backwards to the stem cell that originally generated them, or even, you know, make them somehow biologically younger? The idea of reprogramming your cells to slow down aging is not that new. In 2012, a Japanese scientist

and former surgeon named Shinya Yamanaka won the Nobel Prize for his discovery. Yamanaka figured out that you can use four special genes to reset your cells back into stem cells, and that set of four genes are called the Yamanaka factors. They contain instructions that can reset a cell back to an undifferentiated state, making it like new again, essentially rewriting the cell's program and guiding it back to a more flexible, stem-like state. This was a big deal for aging science. These newly reset cells, known as induced pluripotent stem cells, can then turn into any type of cell you need and could potentially be used to grow new tissues or organs like younger skin or a new heart. Typically, when researchers do cellular reprogramming in the lab, they use an inactivated virus to inject the Yamanaka factors. It's pretty much the same technique they use when you get a vaccine. So, essentially, you have a virus,

and what this virus does is it has those four factors, and it transports them to the cells. And, you know, they have to be regulated, so you don't want too much of it or too little. So you have to get it right, but at least in animal models, this is possible to do now. Hilary: In 2006, Yamanaka showed this can be done in mice. Then in 2007, the next year, he started on human cells, first with skin, and his experiment was quite successful. What scientists and some startups are trying to do now is to partially reprogram some cells so they act younger but don't go all the way back to being an embryonic stem cell again. It retains its identity. It remains a liver cell or a brain cell or a skin cell, but it's rejuvenated. And so that has a lot of potential, because if you can rejuvenate cells

without them losing their identity, that's what you want. But even if these kinds of treatments become available, it wouldn't be like an 80-year-old can suddenly turn 20 again. Maybe it could be rewinding that receding hairline, ditching arthritis, regenerating heart muscle after a heart attack, or healing neurons in your retina so you can see better as you age. I personally would love it if they could regenerate cartilage in my joints, you know, at my age. That would be great. And also, while they're at it, they could also regenerate hair, you know? So that would be a billion-dollar, multibillion-dollar discovery if you could safely regenerate hair in bald men, OK? There are even loftier goals, like curing Parkinson's, regrowing parts of the brain, or rejuvenating your entire body. If you have a young brain, it doesn't develop Alzheimer's or dementia anymore.

So if you can turn your brain young, you will make you resilient to diseases. Maybe even you will treat and cure diseases. We don't know. So that is the promise of the field, is that if you make your organs younger, they'll be more resilient to diseases. Now, most of these ideas are in the testing and research stage and not available as treatments just yet, but some scientists are close. I chatted with Johnny Huard, who's restoring joint cartilage for elite athletes using their own stem cells. We take your bone marrow that contains stem cells and we reinject that into your knee. He's also experimenting with one form of cellular reprogramming using so-called epigenetic drugs, which can change the way our genes behave, in some cases, making them act younger again. We have used cells from old people. They came in and we took the cells, came in the lab, looked at their epigenetic expression was going down,

use epigenetic drug to bring this back up, and the cells look younger. So would you say that that's a form of cellular reprogramming then, what you're doing with those patients? Yes, it is a form of cellular reprogramming, because what I did is I harvested them from you, took drugs to regulate your epigenetic expression, and made those cells younger. So I rejuvenated your cells. But so far, this treatment is just lab work. It would eventually require FDA approval to put the reprogrammed cells back into people's bodies. I'm not saying that, you know, this thing will never be approved three years from now, but it's not approved today. But the potential of this technology has sparked visionary ideas about the future. I imagine a future where children or babies, even before they're born, they're engineered not to age, or at least engineered to be resistant to diseases like Alzheimer's disease.

If you cure aging, and people have the mortality of young adults, then they would live thousands of years. You could still die, of course, but you wouldn't have this exponential increase in mortality. Hilary: Recently, we've seen an explosion of research into this area, and money is flocking into cellular reprogramming and other longevity treatments. Jeff Bezos, for example, is an investor in Altos Labs. Altos is a pretty secretive startup based in California that has recruited some of the most elite aging scientists in the world. The company has at least $3 billion in funding. Another big-deal longevity scientist is Harvard professor David Sinclair. He's behind a bunch of different longevity companies, but he has experimented with cellular reprogramming already on mice and monkeys, and he's hoping to do people next. For example, he conducted an experiment with two mice from the same litter, same DNA. They're like twins, except one is biologically older now,

because it's had its DNA manipulated to act older, mimicking the stress that a body goes through as it ages. Then, Sinclair's team says they use cellular reprogramming to restore the old mouse's organs back to a more youthful state. For example, they found that they could safely reverse age-related blindness and rejuvenate the kidneys and the muscle in the mouse. Sinclair started a private company called Life Biosciences. It's raised at least $175 million so far. They're gunning to get this technology into people's eyeballs and cure age-related blindness. He says the eye injection will be ready soon, maybe within a year or two, but it remains to be seen how quickly it can actually move from labs into clinics. And there are other people you may know of who are investing in cellular reprogramming, too. Sam Altman, the billionaire behind ChatGPT, is also gunning for cellular reprogramming.

He's poured $180 million into his longevity startup, Retro Biosciences. I interviewed the CEO of Retro Biosciences, and he told me they're trying a slightly different approach to cellular reprogramming. Take the cells out of someone's body, then reprogram them, and pop them back in. He thinks it might be safer that way. João: The field is maturing because people and investors and rich folks think that there's going to be commercial outputs in it, that they'll be able to make money out of it. That means that we're going to be able to have a product from the field, which is what I want. Hilary: People love to hear that aging is going to be solved and we're all going to live healthily for a very long time. But the reality is, biology's kind of complicated. Tweak a gene here, insert a new program there, and you'll likely kick off multiple other processes.

in the body, including some that could be harmful and may not be immediately obvious, either. Mice have benefited from this kind of reprogramming, but to go from there to ask, you know, can we now start using this in humans? It's a long stretch. And the reason is that we would want to make sure that over decades, you know, it's not going to increase the risk of cancer. What's the point of living an extra 10 years if it's going to cause cancer, increase the risk of cancer before that? The point Ramakrishnan raises here is important. In the early days of using Yamanaka's reprogramming technique, scientists often saw that cells they created could form teratomas, which are a type of tumor. This happened because two of the four genes used in the reprogramming process are oncogenes. Oncogenes are genes that can divide indefinitely,

and that poses a cancer risk. Always keep in mind that an immortal cell is a cancer cell. So, the big danger of partial reprogramming and cell rejuvenation or reprogramming itself is cancer. So, we actually know from studies in mice that if you reprogram the cells a lot, in a mouse, they become cancer. And obviously, you don't want that. So, there is this balance you have to achieve. You want to do it in a safe way that allows to rejuvenate cells without turning them into cancer. There's also a chance that continuously expressing these Yamanaka factors could lead to liver failure or make your intestines shut down. And there may be other toxic effects we haven't even considered yet. I think for several years now, we've seen the Silicon Valley billionaires trying to go after the medical field, and pretty limited success. One of the most stunning and memorable failures in recent memory was probably the blood-testing company Theranos, which ended up basically being a total sham.

These tech entrepreneurs, CEOs, businesspeople, and billionaires have all been really successful in the world of computing and technology, and it seems like they're trying to take this very same technological approach to what are very complex, poorly understood biological problems. So it remains to be seen if you can reprogram a person like you would a computer. But it's an idea that's attracting a lot of money and a lot of scientists. I think it's wonderful that there is more activity, there's more interest, and there's more investment in the field. It just shows that there's more potential. Curing aging would be a monumental achievement, and it would be a huge change in medicine, in healthcare, in society. And I think that would be magnificent and a huge triumph of civilization.

Can The Billion-Dollar Bet On Biotech Reverse Aging? | Life Extended | Business Insider

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Business Insider

Startups are racing to develop anti-aging technology, with billionaires investing heavily in the effort.

Scientists are focusing on cellular reprogramming to rejuvenate the body, with potential results in just a few years.

The decline in stem cells' number and efficiency as we age contributes to slower healing and more signs of aging, leading to the accumulation of damage and dysfunction over time.

DNA damage over time causes glitches in our human programming, leading to issues in cell function and contributing to aging.

Shinya Yamanaka's discovery of the Yamanaka factors in 2012 provided a method to reset differentiated cells back to their stem cell state, offering potential for tissue and organ regeneration.

Researchers are now exploring partial reprogramming of cells to make them act younger while retaining their identity, aiming to rejuvenate cells and combat the effects of aging.

Regenerative treatments aim to reverse the effects of aging, such as hair loss, joint pain, and heart muscle damage.

Scientists are exploring cellular reprogramming and epigenetic drugs to make old cells behave younger.

While these ideas are still in the research stage, there is potential for future treatments to prevent aging and resist diseases like Alzheimer's.

Research into curing aging has surged, with significant funding flowing into cellular reprogramming and longevity treatments.

Notable investors include Jeff Bezos and Sam Altman, with startups like Altos Labs and Retro Biosciences leading the charge.

Harvard professor David Sinclair's experiments on mice and monkeys aim to replicate the success of cellular reprogramming in humans, with a focus on reversing age-related conditions.

The Risks and Potential of Cell Reprogramming

Cell reprogramming has shown promise in mice, but its application in humans raises concerns about increasing cancer risk.

The use of oncogenes in the reprogramming process poses a danger, as immortal cells can lead to cancer.

While the idea of reprogramming humans is attracting significant interest and investment, the complexity of biological systems makes it uncertain if the approach will be successful.