The Top 8 Things to Know About Anti-Aging Research Right Now
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Dr. Michael West has a storied legacy in the world of aging research. Twenty years ago, the company he started, Geron, hit upon a major breakthrough when his scientists isolated the active component for the gene that confers immortality to cells, called telomerase.
In the twenty years since, a new field has emerged: the science of extending the human "healthspan."
He was in the lab when scientists for the first time artificially turned on the gene in some skin cells donated by Dr. Leonard Hayflick, the man who had discovered back in 1965 that human cells age over time. Sure enough, with Geron's intervention, Hayflick's skin cells became immortal in the dish, and the landmark paper was published in Science in 1998.
In the twenty years since, a new field has emerged: the science of extending the human "healthspan" – the length of time people can live free of diseases related to aging. A substantial amount of preclinical and some clinical research is now underway, backed by heavy investments from some of the world's largest companies.
Today, Dr. West is the CEO of AgeX Therapeutics, a biotech company that is developing novel therapeutics to target human aging and age-related degenerative diseases using pluripotent stem cells. Dr. West recently shared some key insights with Editor-in-Chief Kira Peikoff about what's happening in this exciting space.
1) Pluripotent stem cells have opened the door for the first time in human history to manufacturing young cells and young tissue of any kind.
These are the body's master cells: They are self-replicating, and they can potentially give rise to any cell or tissue the body needs to repair itself. This year marks the 20th anniversary since their isolation for the first time in a lab.
"People in biotech say that the time from lab to discovery in products is about 20 years," West says. "But the good news is we're at that 20-year mark now, so you're seeing an explosive growth of applications. We can now make all cell types of the human body in a scalable manner."
2) Early human development could hold the key to unlocking the mystery of aging.
West believes that two things occur when the body forms in utero: telomerase, the immortalizing gene, gets turned off very early in development in the body cells like skin, liver, and nerves. Additionally, he thinks that a second genetic switch gets turned off that holds the potential for regeneration after injury.
"These insights open the door to intervention by the transfer of telomerase into the cells of the body."
"Very early when the body is first forming, if you cut the skin, it will not respond by scarring, but will regenerate scarlessly," he says. "But that potential gets turned off once the body is formed, about 8 weeks after fertilization. Then, you accumulate damage over a lifetime. Not only do cells have a finite capacity to replicate, but you have tissue damage."
However, there are animals in nature whose telomerase is never turned off, or whose regenerative ability is never turned off. The flatworm, for example, can regenerate its own head if it gets cut off, and it also shows no detectable aging. Lobsters are believed to be similar. (That's not to say it can't get caught and eaten for dinner.)
"These insights open the door to intervention by the transfer of telomerase into the cells of the body, or understanding how regeneration gets turned off, and then turning it back on," West says. "That's well within the power of modern medical research to understand."
3) Companies are investing tremendous resources into the anti-aging gold rush.
Devising interventions is the mission of AgeX, a subsidiary of BioTime, as well as a number of other companies.
"We're seeing a mad rush," West says. There's Google's Calico, which recently announced, with AbbVie Inc., another $1 billion into research for age-related diseases, on top of the previous $1.5 billion investment.
Other notable players include Unity Biotechnology, Samumed, Human Longevity Inc., RestorBio, Rejuvenate Bio,and Juvenescence (which is also an investor in AgeX).
"These are products in development by our company and others that the baby boomers can reasonably anticipate being available within their lifetimes."
4) The majority of clinical applications are still years away.
"What we've learned about turning back on this regenerative state, called induced tissue regeneration, is that the majority of the clinical implications are years away and will require years of clinical trials before potential FDA approval and marketing to the public," West says. "But we have found some potential near-term applications that we think may have a much faster track to commercialization. As you can imagine, we are all over those."
BioTime, Inc., AgeX's parent, has a regenerative medicine product in clinical trials for age-related macular degeneration, the leading cause of blindness in an aging population. While not yet approved by the FDA, BioTime has reported continued progress in the clinical development of the product now in Phase II trials.
Dr. Michael West, CEO of AgeX
Citi recently issued a major report, Disruptive Innovations VI, that included "Anti-Aging Medicines" as the number two innovation for investors to keep an eye on, and predicted that the first anti-aging therapies could receive regulatory approval by 2023.
5) Few, if any, medical interventions are available today that are proven to markedly slow aging - yet. But the Baby Boomers are not necessarily out of luck.
Buyer beware of any claims in the marketplace that a given skin cream or stem cell product will extend your life. More than likely, they won't.
"There are a lot of people trying to cash in on the aging baby boom population," West warns.
"When you hear claims of stem cell products that you can get now, it's important to understand that they are likely not based on pluripotent stem cell technology. Also, they are usually not products approved by the FDA, having gone through clinical trials to demonstrate safety and efficacy."
However, an array of young pluripotent stem cell-derived therapies are on a development track for future approvals.
One example is another program at AgeX: the manufacture of brown fat cells; these cells burn calories rather than store them. They burn circulating fat like triglycerides and sugar in the blood and generate heat.
"You lose brown fat in aging, and animal models suggest that if you restore that tissue, you can restore a metabolic balance to be more like what you had when you were young," says West. "When I was 18, I could drink milkshakes all day long and not gain an ounce. But at 50 or 60, most of us would rapidly put on weight. Why? We believe that one important factor is that with age, you lose this brown fat tissue. The loss throws your metabolism off balance. So the solution is conceptually simple, we plan to make young brown fat cells for transplantation to reset the balance, potentially to treat Type II diabetes or even obesity.
"These are products in development by our company and others that the baby boomers can reasonably anticipate being available within their lifetimes."
6) There is an ethical debate about how far to apply this new science.
Some people are speculating about whether genetic engineering might one day be used to program longer lifespans into humans at the earliest stages of development. (Note: it is against the law across the Western world to edit human embryos intended for reproduction, although just last week, Chinese scientists used CRISPR to repair a disease-causing mutation in viable human embryos.)
West sounds a cautionary note about such interventions meant to lengthen life. "For people who think not just about the science, but the ethics, safety is a major concern. It's entirely possible to genetically engineer babies, but when you make such modifications, it's an experiment, not just in human cells in a dish, but in a human being. I have a great reticence to put any human at risk unless it's a case where the person is suffering with a life-threatening disease, and the potential therapy is their last best hope."
"I have no doubt, zero doubt, that in the foreseeable future, we'll hear of a person who has lived to about 150."
7) The biggest challenge of intervening in human aging is cultural denial.
"The prospect of intervening in a profound way in human aging is still not seen as credible by the vast majority of thoughtful people around the world," West laments.
"Aging is a universal phenomenon, it's mankind's greatest enemy, but as a species we've adapted to the realities of finite lifespans and death. We have a whole infrastructure of belief systems around this, and many people see it as inevitable."
8) The lifespan for healthy children born today could surpass anything humanity has ever seen.
"It is at least 150 years of age," West predicts. "I have no doubt, zero doubt, that in the foreseeable future, we'll hear of a person who has lived to about 150. We know now it's possible. I've never said that publicly before, but I am comfortable now with the prediction. And, of course, if some people now living could live to 150 years of age, we have the prospect of them living to see even more powerful therapies. So, the question now is, what kind of a world are we going to make for future generations?"
[Editor's Note: Check out our latest video, which was inspired by Dr. West's exclusive prediction to leapsmag.]
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”
Since the early 2000s, AI systems have eliminated more than 1.7 million jobs, and that number will only increase as AI improves. Some research estimates that by 2025, AI will eliminate more than 85 million jobs.
But for all the talk about job security, AI is also proving to be a powerful tool in healthcare—specifically, cancer detection. One recently published study has shown that, remarkably, artificial intelligence was able to detect 20 percent more cancers in imaging scans than radiologists alone.
Published in The Lancet Oncology, the study analyzed the scans of 80,000 Swedish women with a moderate hereditary risk of breast cancer who had undergone a mammogram between April 2021 and July 2022. Half of these scans were read by AI and then a radiologist to double-check the findings. The second group of scans was read by two researchers without the help of AI. (Currently, the standard of care across Europe is to have two radiologists analyze a scan before diagnosing a patient with breast cancer.)
The study showed that the AI group detected cancer in 6 out of every 1,000 scans, while the radiologists detected cancer in 5 per 1,000 scans. In other words, AI found 20 percent more cancers than the highly-trained radiologists.
Scientists have been using MRI images (like the ones pictured here) to train artificial intelligence to detect cancers earlier and with more accuracy. Here, MIT's AI system, MIRAI, looks for patterns in a patient's mammograms to detect breast cancer earlier than ever before. news.mit.edu
But even though the AI was better able to pinpoint cancer on an image, it doesn’t mean radiologists will soon be out of a job. Dr. Laura Heacock, a breast radiologist at NYU, said in an interview with CNN that radiologists do much more than simply screening mammograms, and that even well-trained technology can make errors. “These tools work best when paired with highly-trained radiologists who make the final call on your mammogram. Think of it as a tool like a stethoscope for a cardiologist.”
AI is still an emerging technology, but more and more doctors are using them to detect different cancers. For example, researchers at MIT have developed a program called MIRAI, which looks at patterns in patient mammograms across a series of scans and uses an algorithm to model a patient's risk of developing breast cancer over time. The program was "trained" with more than 200,000 breast imaging scans from Massachusetts General Hospital and has been tested on over 100,000 women in different hospitals across the world. According to MIT, MIRAI "has been shown to be more accurate in predicting the risk for developing breast cancer in the short term (over a 3-year period) compared to traditional tools." It has also been able to detect breast cancer up to five years before a patient receives a diagnosis.
The challenges for cancer-detecting AI tools now is not just accuracy. AI tools are also being challenged to perform consistently well across different ages, races, and breast density profiles, particularly given the increased risks that different women face. For example, Black women are 42 percent more likely than white women to die from breast cancer, despite having nearly the same rates of breast cancer as white women. Recently, an FDA-approved AI device for screening breast cancer has come under fire for wrongly detecting cancer in Black patients significantly more often than white patients.
As AI technology improves, radiologists will be able to accurately scan a more diverse set of patients at a larger volume than ever before, potentially saving more lives than ever.