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.

A birthday celebration in the future for someone reaching 150 years old.
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.
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.
Pioneering XPRIZEs, Longevity and Mindset with Dr. Peter Diamandis
XPRIZE founder and chairman Peter Diamandis launches XPRIZE Healthspan at an event on November 29.
A new competition by the XPRIZE Foundation is offering $101 million to researchers who discover therapies that give a boost to people aged 65-80 so their bodies perform more like when they were middle-aged.
For today’s podcast episode, I talked with Dr. Peter Diamandis, XPRIZE’s founder and executive chairman. Under Peter’s leadership, XPRIZE has launched 27 previous competitions with over $300 million in prize purses. The latest contest aims to enhance healthspan, or the period of life when older people can play with their grandkids without any restriction, disability or disease. Such breakthroughs could help prevent chronic diseases that are closely linked to aging. These illnesses are costly to manage and threaten to overwhelm the healthcare system, as the number of Americans over age 65 is rising fast.
In this competition, called XPRIZE Healthspan, multiple awards are available, depending on what’s achieved, with support from the nonprofit Hevolution Foundation and Chip Wilson, the founder of Lululemon and nonprofit SOLVE FSHD. The biggest prize, $81 million, is for improvements in cognition, muscle and immunity by 20 years. An improvement of 15 years will net $71 million, and 10 years will net $61 million.
In our conversation for this episode, Peter talks about his plans for XPRIZE Healthspan and why exponential technologies make the current era - even with all of its challenges - the most exciting time in human history. We discuss the best mental outlook that supports a person in becoming truly innovative, as well as the downsides of too much risk aversion. We talk about how to overcome the negativity bias in ourselves and in mainstream media, how Peter has shifted his own mindset to become more positive over the years, how to inspire a culture of innovation, Peter’s personal recommendations for lifestyle strategies to live longer and healthier, the innovations we can expect in various fields by 2030, the future of education and the importance of democratizing tech and innovation.
In addition to Peter’s pioneering leadership of XPRIZE, he is also the Executive Founder of Singularity University. In 2014, he was named by Fortune as one of the “World’s 50 Greatest Leaders.” As an entrepreneur, he’s started over 25 companies in the areas of health-tech, space, venture capital and education. He’s Co-founder and Vice-Chairman of two public companies, Celularity and Vaxxinity, plus being Co-founder & Chairman of Fountain Life, a fully-integrated platform delivering predictive, preventative, personalized and data-driven health. He also serves as Co-founder of BOLD Capital Partners, a venture fund with a half-billion dollars under management being invested in exponential technologies and longevity companies. Peter is a New York Times Bestselling author of four books, noted during our conversation and in the show notes of this episode. He has degrees in molecular genetics and aerospace engineering from MIT and holds an M.D. from Harvard Medical School.
Show links
- Peter Diamandis bio
- New XPRIZE Healthspan
- Peter Diamandis books
- 27 XPRIZE competitions and counting
- Life Force by Peter Diamandis and Tony Robbins
- Peter Diamandis Twitter
- Longevity Insider newsletter – AI identifies the news
- Peter Diamandis Longevity Handbook
- Hevolution funding for longevity
XPRIZE Founder Peter Diamandis speaks with Mehmoud Khan, CEO of Hevolution Foundation, at the launch of XPRIZE Healthspan.
Hevolution Foundation
Matt Fuchs is the editor-in-chief of Leaps.org and Making Sense of Science. He is also a contributing reporter to the Washington Post and has written for the New York Times, Time Magazine, WIRED and the Washington Post Magazine, among other outlets. Follow him @fuchswriter.
Important findings are starting to emerge from research on how genes shape the human response to the Covid virus.
From infections with no symptoms to why men are more likely to be hospitalized in the ICU and die of COVID-19, new research shows that your genes play a significant role
Early in the pandemic, genetic research focused on the virus because it was readily available. Plus, the virus contains only 30,000 bases in a dozen functional genes, so it's relatively easy and affordable to sequence. Additionally, the rapid mutation of the virus and its ability to escape antibody control fueled waves of different variants and provided a reason to follow viral genetics.
In comparison, there are many more genes of the human immune system and cellular functions that affect viral replication, with about 3.2 billion base pairs. Human studies require samples from large numbers of people, the analysis of each sample is vastly more complex, and sophisticated computer analysis often is required to make sense of the raw data. All of this takes time and large amounts of money, but important findings are beginning to emerge.
Asymptomatics
About half the people exposed to SARS-CoV-2, the virus that causes the COVID-19 disease, never develop symptoms of this disease, or their symptoms are so mild they often go unnoticed. One piece of understanding the phenomena came when researchers showed that exposure to OC43, a common coronavirus that results in symptoms of a cold, generates immune system T cells that also help protect against SARS-CoV-2.
Jill Hollenbach, an immunologist at the University of California at San Francisco, sought to identify the gene behind that immune protection. Most COVID-19 genetic studies are done with the most seriously ill patients because they are hospitalized and thus available. “But 99 percent of people who get it will never see the inside of a hospital for COVID-19,” she says. “They are home, they are not interacting with the health care system.”
Early in the pandemic, when most labs were shut down, she tapped into the National Bone Marrow Donor Program database. It contains detailed information on donor human leukocyte antigens (HLAs), key genes in the immune system that must match up between donor and recipient for successful transplants of marrow or organs. Each HLA can contain alleles, slight molecular differences in the DNA of the HLA, which can affect its function. Potential HLA combinations can number in the tens of thousands across the world, says Hollenbach, but each person has a smaller number of those possible variants.
She teamed up with the COVID-19 Citizen Science Study a smartphone-based study to track COVID-19 symptoms and outcomes, to ask persons in the bone marrow donor registry about COVID-19. The study enlisted more than 30,000 volunteers. Those volunteers already had their HLAs annotated by the registry, and 1,428 tested positive for the virus.
Analyzing five key HLAs, she found an allele in the gene HLA-B*15:01 that was significantly overrepresented in people who didn’t have any symptoms. The effect was even stronger if a person had inherited the allele from both parents; these persons were “more than eight times more likely to remain asymptomatic than persons who did not carry the genetic variant,” she says. Altogether this HLA was present in about 10 percent of the general European population but double that percentage in the asymptomatic group. Hollenbach and her colleagues were able confirm this in other different groups of patients.
What made the allele so potent against SARS-CoV-2? Part of the answer came from x-ray crystallography. A key element was the molecular shape of parts of the cold virus OC43 and SARS-CoV-2. They were virtually identical, and the allele could bind very tightly to them, present their molecular antigens to T cells, and generate an extremely potent T cell response to the viruses. And “for whatever reasons that generated a lot of memory T cells that are going to stick around for a long time,” says Hollenbach. “This T cell response is very early in infection and ramps up very quickly, even before the antibody response.”
Understanding the genetics of the immune response to SARS-CoV-2 is important because it provides clues into the conditions of T cells and antigens that support a response without any symptoms, she says. “It gives us an opportunity to think about whether this might be a vaccine design strategy.”
Dead men
A researcher at the Leibniz Institute of Virology in Hamburg Germany, Guelsah Gabriel, was drawn to a question at the other end of the COVID-19 spectrum: why men more likely to be hospitalized and die from the infection. It wasn't that men were any more likely to be exposed to the virus but more likely, how their immune system reacted to it
Several studies had noted that testosterone levels were significantly lower in men hospitalized with COVID-19. And, in general, the lower the testosterone, the worse the prognosis. A year after recovery, about 30 percent of men still had lower than normal levels of testosterone, a condition known as hypogonadism. Most of the men also had elevated levels of estradiol, a female hormone (https://pubmed.ncbi.nlm.nih.gov/34402750/).
Every cell has a sex, expressing receptors for male and female hormones on their surface. Hormones docking with these receptors affect the cells' internal function and the signals they send to other cells. The number and role of these receptors varies from tissue to tissue.
Gabriel began her search by examining whole exome sequences, the protein-coding part of the genome, for key enzymes involved in the metabolism of sex hormones. The research team quickly zeroed in on CYP19A1, an enzyme that converts testosterone to estradiol. The gene that produces this enzyme has a number of different alleles, the molecular variants that affect the enzyme's rate of metabolizing the sex hormones. One genetic variant, CYP19A1 (Thr201Met), is typically found in 6.2 percent of all people, both men and women, but remarkably, they found it in 68.7 percent of men who were hospitalized with COVID-19.
Lung surprise
Lungs are the tissue most affected in COVID-19 disease. Gabriel wondered if the virus might be affecting expression of their target gene in the lung so that it produces more of the enzyme that converts testosterone to estradiol. Studying cells in a petri dish, they saw no change in gene expression when they infected cells of lung tissue with influenza and the original SARS-CoV viruses that caused the SARS outbreak in 2002. But exposure to SARS-CoV-2, the virus responsible for COVID-19, increased gene expression up to 40-fold, Gabriel says.
Did the same thing happen in humans? Autopsy examination of patients in three different cites found that “CYP19A1 was abundantly expressed in the lungs of COVID-19 males but not those who died of other respiratory infections,” says Gabriel. This increased enzyme production led likely to higher levels of estradiol in the lungs of men, which “is highly inflammatory, damages the tissue, and can result in fibrosis or scarring that inhibits lung function and repair long after the virus itself has disappeared.” Somehow the virus had acquired the capacity to upregulate expression of CYP19A1.
Only two COVID-19 positive females showed increased expression of this gene. The menopause status of these women, or whether they were on hormone replacement therapy was not known. That could be important because female hormones have a protective effect for cardiovascular disease, which women often lose after going through menopause, especially if they don’t start hormone replacement therapy. That sex-specific protection might also extend to COVID-19 and merits further study.
The team was able to confirm their findings in golden hamsters, the animal model of choice for studying COVID-19. Testosterone levels in male animals dropped 5-fold three days after infection and began to recover as viral levels declined. CYP19A1 transcription increased up to 15-fold in the lungs of the male but not the females. The study authors wrote, “Virus replication in the male lungs was negatively associated with testosterone levels.”
The medical community studying COVID-19 has slowly come to recognize the importance of adipose tissue, or fat cells. They are known to express abundant levels of CYP19A1 and play a significant role as metabolic tissue in COVID-19. Gabriel adds, “One of the key findings of our study is that upon SARS-CoV-2 infection, the lung suddenly turns into a metabolic organ by highly expressing” CYP19A1.
She also found evidence that SARS-CoV-2 can infect the gonads of hamsters, thereby likely depressing circulating levels of sex hormones. The researchers did not have autopsy samples to confirm this in humans, but others have shown that the virus can replicate in those tissues.
A possible treatment
Back in the lab, substituting low and high doses of testosterone in SARS-COV-2 infected male hamsters had opposite effects depending on testosterone dosage used. Gabriel says that hormone levels can vary so much, depending on health status and age and even may change throughout the day, that “it probably is much better to inhibit the enzyme” produced by CYP19A1 than try to balance the hormones.
Results were better with letrozole, a drug approved to treat hypogonadism in males, which reduces estradiol levels. The drug also showed benefit in male hamsters in terms of less severe disease and faster recovery. She says more details need to be worked out in using letrozole to treat COVID-19, but they are talking with hospitals about clinical trials of the drug.
Gabriel has proposed a four hit explanation of how COVID-19 can be so deadly for men: the metabolic quartet. First is the genetic risk factor of CYP19A1 (Thr201Met), then comes SARS-CoV-2 infection that induces even greater expression of this gene and the deleterious increase of estradiol in the lung. Age-related hypogonadism and the heightened inflammation of obesity, known to affect CYP19A1 activity, are contributing factors in this deadly perfect storm of events.
Studying host genetics, says Gabriel, can reveal new mechanisms that yield promising avenues for further study. It’s also uniting different fields of science into a new, collaborative approach they’re calling “infection endocrinology,” she says.