On Dec. 2, 2020, the international journal Nature splashed the cover with a retinal image and the bold headline "Turning back time." A title more fitting for a movie or novel referred to a research paper by David Sinclair of Harvard Medical School. The Harvard team said it delivered three genes to the retinas of mice with glaucoma and aged mice to restore vision. The neurons were rejuvenated to the state of healthy young mice.
A movie-like story of turning old cells young has become reality. The biotech company Life Biosciences, founded by Sinclair, applied to glaucoma patients the same method released in Nature six years ago. The company received phase 1 clinical trial approval in Jan. this year from the U.S. Food and Drug Administration (FDA) for ER-100, an ophthalmic disease therapy, and began dosing actual patients in Mar.. In human history, this is the first time an attempt to reverse the biological age of cells has been applied to actual humans.
If the body became younger, not merely treating or preventing disease, it could generate immense economic value. Healthspan would increase dramatically, reducing medical costs while sharply expanding the productive workforce. That is why Silicon Valley heavyweights such as the founders of Google, OpenAI, and Amazon are investing trillions of won in cellular rejuvenation corporations. The age of reversing aging by turning back the biological clock has dawned.
Beyond "parts replacement" to "cell rebooting"
The principle of cellular rejuvenation was born 20 years ago. In 2006, Yamanaka Shinya of Kyoto University said he reverted fully grown skin cells to a primitive embryonic stem cell state by introducing four genes. Because, like embryonic stem cells in a fertilized egg (embryo), they can differentiate into all cells of the human body, they were named induced pluripotent stem cells (iPS cells). Yamanaka received the 2012 Nobel Prize in Physiology or Medicine for this work.
Because fully grown skin cells are reversed back to an initial state and have the "pluripotency" to grow into various human cells like embryonic stem cells, iPS cells raised hopes of fundamentally treating disease. In particular, embryonic stem cells had sparked bioethics controversy because they require destroying a fertilized egg, but iPS cells are made from the patient's own cells, avoiding that problem.
Yamanaka differentiated iPS cells into retinal cells and achieved results treating patients with macular degeneration at risk of blindness. In the United States, researchers are trying to treat Parkinson's disease by making iPS cells into dopamine neurons. The Harvard team went a step further. They inject into patients' cells the genes Oct4, Sox2, Klf4, and c-Myc, known as the "Yamanaka factors," to make them young directly. In other words, it is not parts replacement but like reinstalling and upgrading the program.
The problem is that using all the Yamanaka factors pushes neurons all the way back to the early stem cell stage, so they can no longer function. This can allow cells to proliferate at will and cause cancer. In 2020 animal experiments, the Harvard team achieved "partial rejuvenation," or reprogramming that turns back time while maintaining the identity of retinal neurons, by using only three factors—OSK—omitting c-Myc from the Yamanaka factors. This year's clinical trial uses the same approach.
Partial rejuvenation is likened to a software reboot that optimizes the system and fixes errors to speed up an old computer instead of replacing the hardware wholesale. With a reboot, you do not have to go through the hassle of creating iPS cells outside the body, redifferentiating them into replacement cells, and injecting them; by delivering only genes, you can directly turn old or diseased cells young. In Feb., Sinclair said at the World Governments Summit in the United Arab Emirates (UAE), "Aging is not destiny; it is increasingly treatable," and noted, "The human body is like a computer—it can be programmed, reprogrammed, and rebooted to become young again."
Skin grows younger and memory improves
Until now, aging was believed to occur as mutations arise in genes within DNA. If some of the information encoded in genes is lost or altered, cells lose function, ultimately leading to organ damage and disease. But recently, observations in humans and mice have shown cases where even with many gene mutations, aging does not accelerate, and conversely, aging occurs despite few gene mutations.
Scientists found that while the DNA genetic information inherited at birth remains unchanged, gene function later changes through structural modifications such as the attachment of other molecules to DNA during growth. Such structural changes to DNA are called the epigenome. The Harvard team used the three Yamanaka factors to modify the epigenome and erase signs of aging in cells.
Another key to partial rejuvenation is timing control. In 2016, a team led by Juan Carlos Izpisua Belmonte at the Salk Institute for Biological Studies in the United States succeeded in repeatedly switching the Yamanaka factors on and off in mice. As a result, experimental animals with progeria, which accelerates aging, lived 30% longer. The team used an antibiotic with proven safety in humans as the switch for the Yamanaka factors. Antibiotics readily cross cell membranes and can easily reach gene control sites.
Partial rejuvenation has recently delivered a string of successes in animal studies. It rejuvenated skin and reduced scarring, and promoted muscle regeneration. Damaged heart cells due to disease were also regenerated. One study found that periodically expressing the Yamanaka factors in old mice improved memory. The scientific community said that if this clinical trial succeeds, it could usher in an era of rejuvenation that not only restores sight to older adults but also makes the liver, kidneys, and even the brain younger.
Silicon Valley tycoons jump in
Advances in cellular rejuvenation have been backed by massive Silicon Valley capital. Altos Labs, funded by Amazon founder Jeff Bezos and DST Global founder Yuri Milner, secured $3 billion (about 4.467 trillion won). This is the largest-ever seed funding for a biotech startup.
In Oct. 2020, Milner invited luminaries including Professors Izpisua Belmonte and Yamanaka to his home in Los Altos Hills, California, for two days to discuss the potential of cellular rejuvenation. Convinced of its promise that day, Milner founded Altos Labs the following year, naming it after the place where the meeting was held. The two professors released that day also joined the company.
Sam Altman, CEO of OpenAI, which developed ChatGPT, invested $180 million (about 268 billion won) in Retro Biosciences, launched in 2022. The company set a goal of extending healthspan by 10 years through cellular rejuvenation. Jeff Bezos and PayPal cofounder Peter Thiel invested in Unity Biotechnology, which is developing anti-aging drugs, and Google cofounders Larry Page and Sergey Brin founded anti-aging corporation Calico in 2013.
Billionaires zeroed in on the vast economic value of age reversal. In 2021, Sinclair, Andrew Scott of London Business School, and Martin Ellison of the University of Oxford's Department of Economics predicted in the international journal Nature Aging that extending humanity's healthspan by one year would generate $38 trillion (about 5,657.4 trillion won) in economic value worldwide.
The researchers quantified that slowing aging itself is far more valuable economically than treating disease. When aging slows, it does not merely extend life; it creates a "compounding effect" by raising the productive age, reducing medical expenditure, and improving quality of life. The team estimated that if healthspan were extended by 10 years, the value would reach a staggering $367 trillion (about 54,631.6 trillion won).
The market is also growing rapidly. In a 2023 report, global market research firm InsightAce Analytic predicted that the anti-aging therapeutics market would grow at a 17.5% compound annual rate from $592 million (about 88 billion won) in 2022 to $2.474 billion (about 3.683 trillion won) in 2031. If the cosmetics market with the same ingredients and mechanisms is included, the size is even larger. In a report released late last year, Precedence Research projected that the global anti-aging market would grow from $77.96 billion (about 11.6 trillion won) in 2025 to $149.54 billion (about 22.3 trillion won) in 2035.
Drugs that target zombie cells boost rejuvenation
Industry is also focusing on age-reversal technologies that remove or neutralize old cells. These include senolytic drugs that dismantle senescent cells and senomorphic drugs that modulate their secretions. Senescent cells are cells that have lost normal function with age but were not cleared by the immune system. They neither die nor work; they just drift in the body and are called "zombie cells." They are known to cause not only aging phenomena such as osteoporosis, osteoarthritis, and muscle loss, but also neurodegenerative diseases such as Alzheimer's and Parkinson's.
Unlike partial rejuvenation, which introduces exogenous genes into the body, senolytics and senomorphics can leverage existing drugs and are expected to reach commercialization sooner. In a report released at the end of 2023, the Korea Institute of Science & Technology Evaluation and Planning (KISTEP) projected that senolytics would be realized by 2025 and cellular rejuvenation technology by 2034. Actual development has been slower than that, but clinical trials are progressing faster.
In 2019, the Mayo Clinic in the United States released the first clinical trial results of removing patients' zombie cells with senolytic drugs. Patients took dasatinib, approved as a leukemia therapy, and quercetin, a plant pigment found in grapes, onions, green tea, apples, strawberries, and ginkgo, showing safety and improved muscle strength. Unity Biotechnology, backed by Bezos and Thiel, completed a phase 2 trial of the senolytic drug UBX1325 in elderly patients with ocular disease.
As senomorphic drugs, the diabetes therapy metformin and the transplant immunosuppressant rapamycin are noted. Both have shown lifespan extension in nematodes and mice. Swiss pharmaceutical company Novartis confirmed that a rapamycin analog improved elderly responses to the flu vaccine by 20%. In terms of immunity, that amounts to a 20% rejuvenation effect.
Korean researchers achieved results by combining senomorphics with cellular partial rejuvenation. A team led by Cho Gwang-hyeon at KAIST reported in 2020 in the Proceedings of the National Academy of Sciences (PNAS) that they temporarily expressed the four Yamanaka factors in aged human skin cells and successfully reverted them to young cells. The team conducted the research with the technology research institute of cosmetics corporation Amorepacific.
Partial dedifferentiation can inadvertently cause cancer. The researchers combined Yamanaka factors with senomorphic drugs to solve this problem. When applied to the world's first engineered aged skin, aging factors disappeared and normal cell function was restored. Amorepacific's technology research institute is developing cosmetics that improve wrinkles in aged skin by identifying senomorphic components from camellia extract.
Hunting for longevity secrets in animals
Biotech corporations are searching for new genes and proteins that induce rejuvenation without side effects beyond the existing Yamanaka factors. To that end, they also study longevity models in nature. The bowhead whale, the longest-lived mammal on Earth, lives more than 200 years. The subterranean naked mole rat is another astonishing research subject. While other mice of similar size live just over three years, they survive more than 10 times longer—over 30 years. In human terms, that would be like living 800 years.
The whale's secret to longevity was DNA repair capacity. When human DNA is battered by the ravages of time, bowhead whale cells repair damage immediately and maintain cellular age. One might think whales, being large, have more cells and thus more mutations, making them prone to cancer. In reality, they rarely get cancer. Because their DNA repair is so exceptional, the chance of mutations arising is low.
The same is true of naked mole rats. In humans and mice, an enzyme protein called cGAS interferes with repairing DNA damaged by aging, but in naked mole rats it works in the opposite way. When researchers induced in fruit flies the same mutation as the naked mole rat's enzyme gene, lifespan increased by 16%. For Korea's life expectancy, that would amount to roughly 12 more years.
Calico, founded by Google, had already selected this animal as a model for longevity research at its launch. Calico also found that naked mole rats essentially do not age until death. In humans, after 30, the risk of death from disease doubles every eight years. Naked mole rats are the only mammals whose mortality risk does not increase with age. Before long, home shopping channels may advertise a "three-piece Yamanaka factor set" with added bowhead whale and naked mole rat DNA.
References
Neuron (2026), DOI: https://doi.org/10.1016/j.neuron.2025.11.028
Cellular Reprogramming (2024), DOI: https://doi.org/10.1089/cell.2023.0041
Cell Reports (2022), DOI: https://doi.org/10.1016/j.celrep.2022.110730
Science (2021), DOI: https://doi.org/10.1126/science.abg5159
Nature (2020), DOI: https://doi.org/10.1038/s41586-020-2975-4
PNAS (2020), DOI: https://doi.org/10.1073/pnas.1920338117
Cell (2016), DOI: https://doi.org/10.1016/j.cell.2016.11.052
Cell (2006), DOI: https://doi.org/10.1016/j.cell.2006.07.024