--- title: Scientist Discovers Aging Clock to Speed and Reverse Aging description: The finding involves mice, but represents an important milestone in understanding what causes cells to age—and potentially how to reverse the process in people. canonical: https://time.com/6246864/reverse-aging-scientists-discover-milestone/ author: Alice Park article:opinion: false article:content_tier: free article:published_time: 2023-01-12T17:38:49.000Z article:modified_time: 2026-08-04T07:49:46.060Z article:section: Health og:title: Scientists Have Reached a Key Milestone in Learning How to Reverse Aging og:description: The finding involves mice, but represents an important milestone in understanding what causes cells to age og:url: https://time.com/6246864/reverse-aging-scientists-discover-milestone/ og:site_name: TIME og:image: https://static.time.com/v3/assets/bltea6093859af6183b/bltde093bcdab65f2d0/6988d9b9bc6cfc69913e2a3c/time-logo.jpg?branch=production og:image:width: 1200 og:image:height: 675 og:image:alt: TIME og:type: article twitter:card: summary_large_image twitter:title: Scientists Have Reached a Key Milestone in Learning How to Reverse Aging twitter:description: The finding involves mice, but represents an important milestone in understanding what causes cells to age twitter:image: https://static.time.com/v3/assets/bltea6093859af6183b/bltde093bcdab65f2d0/6988d9b9bc6cfc69913e2a3c/time-logo.jpg?branch=production --- # Scientists Have Reached a Key Milestone in Learning How to Reverse Aging > Sponsored content. 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Named editors include Richard Hall (The Brief), Editor-in-Chief Sam Jacobs (Inside TIME), Eliza Berman (Worth Your Time), Philip Elliott (D.C. Brief), Justin Worland (Future Proof) and Harry Booth (In the Loop). Health Matters is written by TIME's health desk. #### How do I sign up for a TIME newsletter? Go to time.com/newsletters, choose the newsletters you want and enter your email address. There is no cost and no subscription requirement. ## Video: The Race to Make a Vaccine for Breast Cancer [Watch (HLS stream): The Race to Make a Vaccine for Breast Cancer](https://cdn.jwplayer.com/manifests/W5jcvwLu.m3u8) (8:09)  _Published 2022-10-05. Scientists believe there is a future in which women can be vaccinated against breast cancer._ by [Alice Park](https://time.com/author/alice-park/) and [Video by Andrew. D Johnson](https://time.com/author/andrew-johnson/) Jan 12, 2023 5:38 PM UTC by [Alice Park](https://time.com/author/alice-park/) and [Video by Andrew. D Johnson](https://time.com/author/andrew-johnson/) Jan 12, 2023 5:38 PM UTC It’s been 13 years in the making, but Dr. David Sinclair and his colleagues have finally answered the question of what drives aging. In a [study](https://www.cell.com/cell/fulltext/S0092-8674%2822%2901570-7) published Jan. 12 in _Cell_, Sinclair, a professor of genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, describes a groundbreaking aging clock that can speed up or reverse the aging of cells. Scientists studying aging have debated what drives the process of senescence in cells—and primarily focused on mutations in DNA that can, over time, mess up a cell’s normal operations and trigger the process of cell death. But that theory wasn’t supported by the fact that older people’s cells often were not riddled with mutations, and that animals or people harboring a higher burden of mutated cells don’t seem to [age prematurely](https://time.com/6240674/swedish-concept-aging-kart-besvar/). Sinclair therefore focused on another part of the genome, called the epigenome. Since all cells have the same DNA blueprint, the epigenome is what makes skin cells turn into skin cells and brain cells into brain cells. It does this by providing different instructions to different cells for which genes to turn on, and which to keep silent. [Epigenetics](https://time.com/3911161/explaining-epigenetics-the-health-buzzword-you-need-to-know/) is similar to the instructions dressmakers rely on from patterns to create shirts, pants, or jackets. The starting fabric is the same, but the pattern determines what shape and function the final article of clothing takes. With cells, the epigenetic instructions lead to cells with different physical structures and functions in a process called differentiation. --- ### More from TIME --- In the _Cell_ paper, Sinclair and his team report that not only can they age mice on an accelerated timeline, but they can also reverse the effects of that aging and restore some of the biological signs of youthfulness to the animals. That reversibility makes a strong case for the fact that the main drivers of aging aren’t mutations to the DNA, but miscues in the epigenetic instructions that somehow go awry. Sinclair has long proposed that aging is the result of losing critical instructions that cells need to continue functioning, in what he calls the Information Theory of Aging. “Underlying aging is information that is lost in cells, not just the accumulation of damage,” he says. “That’s a paradigm shift in how to think about aging. “ His latest results seem to support that theory. It’s similar to the way software programs operate off hardware, but sometimes become corrupt and need a reboot, says Sinclair. “If the cause of aging was because a cell became full of mutations, then age reversal would not be possible,” he says. “But by showing that we can reverse the aging process, that shows that the system is intact, that there is a backup copy and the software needs to be rebooted.” In the mice, he and his team developed a way to reboot cells to restart the backup copy of epigenetic instructions, essentially erasing the corrupted signals that put the cells on the path toward aging. They mimicked the effects of aging on the epigenome by introducing breaks in the DNA of young mice. (Outside of the lab, epigenetic changes can be driven by a number of things, including smoking, exposure to pollution and chemicals.) Once “aged” in this way, within a matter of weeks Sinclair saw that the mice began to show signs of older age—including grey fur, lower body weight despite unaltered diet, reduced activity, and increased frailty. _Stay up-to-date on the latest health news, and get expert advice on living well in TIME’s Health Matters newsletter._ [**_Subscribe here._**](https://time.com/newsletters/?source=conversation&newsletter%5Fname=time%5Ffor%5Fhealth) The rebooting came in the form of a gene therapy involving three genes that instruct cells to reprogram themselves—in the case of the mice, the instructions guided the cells to restart the epigenetic changes that defined their identity as, for example, kidney and skin cells, two cell types that are prone to the effects of aging. These genes came from the suite of so-called Yamanaka stem cells factors—a set of four genes that [Nobel](https://healthland.time.com/2012/10/08/stem-cell-scientists-awarded-nobel-prize-in-physiology-and-medicine/) scientist Shinya Yamanaka in 2006 [discovered](https://content.time.com/time/subscriber/article/0,33009,1687011,00.html) can turn back the clock on adult cells to their embryonic, stem cell state so they can start their development, or differentiation process, all over again. Sinclair didn’t want to completely erase the cells’ epigenetic history, just reboot it enough to reset the epigenetic instructions. Using three of the four factors turned back the clock about 57%, enough to make the mice youthful again. “We’re not making stem cells, but turning back the clock so they can regain their identity,” says Sinclair. “I’ve been really surprised by how universally it works. We haven’t found a cell type yet that we can’t age forward and backward.” **Read More:** [_The Best Anti-Aging Serums, Tested and Reviewed_](https://time.com/shopping/article/best-anti-aging-serum/) Rejuvenating cells in mice is one thing, but will the process work in humans? That’s Sinclair’s next step, and his team is already testing the system in non-human primates. The researchers are attaching a biological switch that would allow them to turn the clock on and off by tying the activation of the reprogramming genes to an antibiotic, doxycycline. Giving the animals doxycycline would start reversing the clock, and stopping the drug would halt the process. Sinclair is currently lab-testing the system with human neurons, skin, and fibroblast cells, which contribute to connective tissue. In 2020, Sinclair reported that in mice, the process [restored vision](https://www.nature.com/articles/s41586-020-2975-4) in older animals; the current results show that the system can apply to not just one tissue or organ, but the entire animal. He anticipates eye diseases will be the first condition used to test this aging reversal in people, since the gene therapy can be injected directly into the eye area. “We think of the processes behind aging, and diseases related to aging, as irreversible,” says Sinclair. “In the case of the eye, there is the misconception that you need to regrow new nerves. But in some cases the existing cells are just not functioning, so if you reboot them, they are fine. It’s a new way to think about medicine.” That could mean that a host of diseases—including chronic conditions such as [heart disease](https://time.com/5517619/americans-heart-disease/) and even neurodegenerative disorders like [Alzheimer’s](https://time.com/6237368/alzheimers-disease-drug-lecanemab/)—could be treated in large part by reversing the aging process that leads to them. Even before that happens, the process could be an important new tool for researchers studying these diseases. In most cases, scientists rely on young animals or tissues to model diseases of aging, which doesn’t always faithfully reproduce the condition of aging. The new system “makes the mice very old rapidly, so we can, for example, make human brain tissue the equivalent of what you would find in a 70 year old and use those in the mouse model to study Alzheimer’s disease that way,” Sinclair says. Beyond that, the implications of being able to age and rejuvenate tissues, organs, or even entire animals or people are mind-bending. Sinclair has rejuvenated the eye nerves multiple times, which raises the more existential question for bioethicists and society of considering what it would mean to continually rewind the clock on aging. This study is just the first step in redefining what it means to age, and Sinclair is the first to acknowledge that it raises more questions than answers. “We don’t understand how rejuvenation really works, but we know it works,” he says. “We can use it to rejuvenate parts of the body and hopefully make medicines that will be revolutionary. Now, when I see an older person, I don’t look at them as old, I just look at them as someone whose system needs to be rebooted. It’s no longer a question of if rejuvenation is possible, but a question of when.” ## Transcript Vaccines are often called The Miracle of modern medicine for their ability to Target the immune system against disease-causing, viruses and bacteria. Since they work against infectious diseases, why not against other conditions that have long plagued Humanity like cancer. To say we're working to develop a vaccine to prevent Cancers and individuals for the rest of your life. It sounds like Star Wars but it's not a concept that's totally unchartered me vaccines against human papillomavirus which is causative agent in certain types of human cancers. Work to prevent cancer in those individuals who get vaccinated and so are we? We no longer is nikoli more about the immune system in the last 20 years in the face of cancer. Studies and cancer. And now it's covid that we can bring this knowledge to this big goal of using a new system to prevent all types of cancers and and do so with humility and optimize the immune response against cancer by training cells to recognize tumors as foreign. Once that happens in breast cancer, it may be possible to not only prevent Prince's in people who have already had cancer, but to even prevent it in the first place, I was diagnosed in 1987 and I wasn't treated much differently from what the treatments or today. Oh, wow. Yes, there's a lot of focus on immunotherapy and that's exciting. It's exciting from a research perspective but it hasn't really made a difference in women's lives. Yet, we believe that a vaccine approach is certainly the key and primary prevention or preventing people from getting breast cancer to begin with because we believe that that is the future, that that is one of the areas that we should be focusing on now. We believe not only will it save lives, but it will also be less toxic than existing Therapies. You know, technologies that have have been developed over the past five to ten years. Are number one, immune checkpoint Inhibitors. So, immune checkpoint Inhibitors is a form of therapy that has been you know now approved by the Food and Drug Administration for use in targeting a number of different cancers were, we had has been effective lasso in in certain tumors. And so, the reason that vaccines don't work against metastatic deposits of tumor is because the tumors themselves. Throw up a number of Walls that ultimately prevents the immune response from acting and killing the tumor. So the whole idea just like an infectious disease, vaccine used to identify what's foreign in the tumor as much as possible and to really craft A vaccine that targets what's foreign because that's really word. You know we're going to see the power of the immune response and in shrinking or preventing a cancer is having multiple targets within the tumor. But also having them be very foreign at the Mayo. Clinic Newton has developed a vaccine targeting, a very early form of breast cancer called ductal carcinoma inside you or DC, is he is working with his colleague dr. Amy degnan to test that vaccine experts, have debated in recent years, whether dcis is actually cancer since it involves lesions that remain in the ducts of the breast tissue and don't spread throughout the breast as other forms of breast cancer. Do about 50 1,000 women. A year are diagnosed with DC is in the US and some of those cases will become cancerous. Although doctors, can't predict which one As a result many women with the condition up to have radiation and surgery to remove the lesions to avoid the risk of developing cancer. if the immune system could be trained to attack tcis instead that would potentially help women to avoid the more invasive treatments, which some experts believe might be over treating their condition We are interested in pushing forward, you know, toward a goal of vaccines for breast cancer prevention. And so one strategy to do that is to then evaluate a vaccine that we found was safe and women who had invasive cancer and apply it to women who don't have invasive cancer yet who have this dcis and evaluate what kind of immune response we see in those women. And one of the things that were specifically interested in this study to see is what kind of response do we see in the breast tissue after this vaccine is given, can we find evidence that the immune system is reacting to the vaccine and potentially, you know, trying to clear out these cancer cells in the breast tissue. So, in this trial, we give the vaccine for several doses of the vaccine before surgery, and women who have dcis. And then at the time of We're removing their dcis as we would not normally to treat it, but we're also able to then investigate the breast tissue and the area of DCs and and see what is happening with the immune response there after the vaccine, the team at the Abramson Cancer Center, at Penn Medicine, is studying a different approach to a breast cancer vaccine. They are currently a rolling about 16th bull who have been diagnosed with cancer and who have the genetic mutations, bcra one or bcra to which put them at higher risk of developing breast cancer to see if vaccinating them will lower their chance of recurrence. The researchers also had to study a couple dozen people with the genetic risk, but who has not yet been diagnosed with cancer to see if the vaccine could lower their risk of ever developing the disease. It's a, it's a game changer and we recognize that we have a ways to go. But right now, if you're a 25 year old woman who has undergone genetic testing and is told that you have a safe for me to yishun, you're talkin about raining for the rest of your life for your breasts or deciding to do a bilateral, mastectomy have your breasts removed and at this point we had no effective screening for ovarian cancer. And so we strongly recommend that individuals have their ovaries removed between ages, 35 and 44 a beer, signaling carrier, putting them into early menopause. And with all the attendant Dallas ring consequence that we really have not had great options apart from surgical options. And, you know, we're working on many different types of strategies to try alternative National the natural history. But this concept of immune interception being able to use the immune system to change the natural history for these individual is so critical. We are probably at the end of the era of using cancer, vaccines with great hope in a patient, whose party been treated with everything in the tumor is still Advanced to using these vaccines and all our new knowledge in patients, who are at risk for relapse or individuals who are simply a high risk for cancer and we want to prevent so prevention. 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