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.]
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman