Harvard’s David Sinclair Treats Aging as a Disease and Plans to Launch a Clinical Trial to Prove It

Innovation That Matters

Harvard University’s David Sinclair, world renowned for his anti-aging research, sees no limit on human life span and is collaborating on a clinical trial to evaluate the effectiveness of a new drug aimed at slowing the aging process. 

“There is no maximum human life span,” says Sinclair, Ph.D., who is a professor in the Department of Genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. “Anyone who says that doesn’t know what they are talking about.”

Sinclair hopes to demonstrate what he has been researching, – and talking about, for the past 20 years – that aging is a disease, which can be treated.

“We’re trying to understand not just the hallmarks of aging, or what we might call the symptoms of aging, but what’s driving all of that,” he says. “What is it about a whale that can live 300 years and a tree that can live 2,000 years? What is that process that leads to all the other downstream effects of aging and that leads to all the diseases that we can succumb to as we grow older?”

Together with the FDA, Sinclair and others worked on guidelines for a clinical trial, which he contends will “for the first time, test and hopefully show that we can have not just an impact on the health of individuals, but also their rate of aging.”

If he’s successful, Sinclair has pledged to make the anti-aging medicines available to the entire world, “not just developed countries, because I think this is just too important to provide the drugs to people who can afford them and leave out large sections of the globe.”

He acknowledges the societal implications of extending human life span are enormous and he compares the potential impact of anti-aging drugs to that of vaccines and antibiotics in the 20th century, which “allowed us to reach the level of well-being and wealth that we enjoy now in the developed world.”

Sinclair earned his Ph.D. in molecular genetics at the University of New South Wales in Sydney. He was a postdoctoral researcher at Massachusetts Institute of Technology where he co-discovered a cause of aging for yeast and the role of the SIR2 gene, one of a series of sirtuin genes that exist in all organisms from yeast to humans. In 1999, he joined Harvard Medical School where his laboratory’s research has focused on how sirtuin genes influence diseases and aging,

Sinclair is co-founder of the biotechnology companies Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, EdenRoc Sciences, Liberty Biosecurity, and Life Biosciences; and sits on the boards of several others. He is also co-founder and co-chief editor of the journal Aging.

WuXi AppTec Communications’ interview with Sinclair about his aging research and drug development is part of an exclusive series spotlighting the inside perspectives of thought leaders on topics shaping the future of new medicines.

WuXi: How do you define aging? Is it a disease or a specific group of diseases?

David Sinclair: I define aging as a disease. There’s no question about it in my mind. If you look up a definition of what is a disease and what is aging in the Merck Manual of Geriatrics, the gold standard, you will see that if a deterioration of the body occurs to less than half the population, we call it a disease. If it happens to more than half the population, we call it aging. That’s as simple as it is. It’s a 50 % cut off.

I would argue, first off, that makes aging more important to work on because it affects more people. But also consider this: If you lived in a world where people were healthy to 150 and you started to become frail at 80 people would raise money for you and your family to try to treat your syndrome. Really, it’s all relative as to whether we call something a disease or call it aging.

WuXi: How are you applying your anti-aging research?

David Sinclair: Over the past 20 years, my life has been focused on not just making discoveries, but innovating and working towards making medicines. We have had a number of spinout companies that are currently in clinical trials of drugs that could not just treat one disease, but could treat and delay all diseases of aging.

There are two approaches we’re taking. One is to boost the body’s defenses against deterioration. Back in the early 1990s I was part of a team that worked to discover the role of the sirtuin gene in our bodies’ defenses against aging. The sirtuin gene exists in everything from yeast cells through to humans. We think they are one of the best ways for us to not just treat one disease, but potentially all areas of illness.

The second approach we’re taking is we’re trying to understand not just the hallmarks of aging, or what we might call the symptoms of aging, but what’s driving all of that. Is there a unified process that leads us to have a life span of about 80 years? What is it about a whale that can live 300 years and a tree that can live 2,000 years? What is that process that leads to all the other downstream effects of aging and that leads to all the diseases that we can succumb to as we grow older?

WuXi: What will define success for your research efforts?

David Sinclair: Success for me is that people will be living healthier and longer across the globe. Short term success would be to have one or more medicines that are prescribable for a particular disease. That’s what we are striving for now. But my hope is once these drugs are on the market they can be tested in a wide variety of other diseases that afflict us as we get older, and are safe enough to be used across the planet. I’ve already pledged to make the drugs that we are developing available to the entire world; not just developed countries, because I think this is just too important to provide the drugs to people who can afford them and leave out large sections of the globe.

WuXi: Which specific disease are you targeting?

David Sinclair: I’m working with numerous companies and they are in clinical trials to treat a whole range of diseases – childhood diseases, rare diseases, and also age-related diseases. The amazing thing about these discoveries in the aging field is that there is a wealth of indications that the drugs can be used for and it’s really a question of what’s their best application and how they can reach the market the fastest because there are patients who are clearly in need of these molecules.

WuXi: Is your goal to treat specific diseases, or do you have a clinical trial focused on extending life span?

David Sinclair: My friend Nir Barzilai (director of the Institute for Aging Research at the Albert Einstein College of Medicine) has one planned called TAME and I’m helping as best I can. We’ve worked with the FDA to draw up guidelines and endpoints for the trial. That’s all in place. We hope that trial will begin this year and for the first time we will be able to test and hopefully show that we can have not just an impact on the health of individuals, but also their rate of aging.

Hopefully before that happens we’re optimistic that we will be able to have the law changed in countries across the world that will recognize the technology is here already to be able to impact people’s lives dramatically and that aging should be defined as a disease that is treatable. And just because it’s common doesn’t mean we should ignore it.

WuXi: How will changing the law to recognize aging as a disease affect research and development?

David Sinclair: We’re on a path to get drugs that extend life span on the market and that’s going to happen whether governments act or not. It’s just a matter of time. But things would be faster and there would be more investment if governments would appreciate and formally recognize aging as a treatable condition so that drug companies and biotechnology companies could be directly reimbursed for helping patients.

There’s this thought that we couldn’t afford the number of people who would ask for these drugs and it’s true. There could be a billion people who would be prescribed these medicines, potentially everybody over the age of 40. But what’s not appreciated is that the cost savings far outweigh the cost of the drug. It’s been calculated that the cost savings just for the U.S. would be in the tens of trillions of dollars per drug, and society would advance to the next level in the same way that vaccines and antibiotics allowed us to reach the level of well-being and wealth that we enjoy now in the developed world.

WuXi: How would you price a drug like this?

David Sinclair: Some of the medicines we’re working on could be relatively cheap. They aren’t expensive to produce. It’s really just a question of how expensive they are to develop. That’s the reason why if the barriers to development were lower, then the cost would also be lower. I could see these drugs being, some of them, less than a dollar a day to extend somebody’s life span by five or 10 years. I have pledged that the drugs we develop will be available globally. I also have pledged that the first country in the world to declare aging a disease will get our first drug at cost for the entire population.

WuXi: How would you describe the recent history of approaches to anti-aging research?

David Sinclair: Anti-aging research had a bad name in the 1980s because there was very little cutting edge science being applied to it. That changed in the 1990s when longevity genes were discovered by geneticists studying model organisms, and now we understand that these same genes are present in our bodies and are largely responsible for the benefits of diet and exercise and are the reason why, when we’re young, we don’t get sick.

Now we’re at the point in human history where we understand what to do, it’s just a matter of doing it, and executing on the drug development programs, and to target the anti-aging pathways that we know to exist. I believe we are no different from all the other organisms whose life spans we’ve extended.

WuXi: How do you see these anti-aging strategies evolving over the next five-to-10 years? Is this the next wave of excitement for Silicon Valley? Or will it evolve more slowly?

David Sinclair: I’ve been commercializing aging research for the past 15 years. It’s only in the last year that interest has gone through the roof from venture capitalists, private individuals, and more recently pharmaceutical companies across the board. That’s happening for two reasons.

One is the world is more optimistic than it used to be, or is living in very good times; and another is that technology, the science, has reached a point where it seems not just feasible to greatly extend human life span, but an inevitability. The companies that are able to dominate that space will be some of the largest companies in the 21st century, rivaling Amazon, Google and Pfizer.

WuXi: Is there a maximum human life span? What would it be?

David Sinclair: There is no maximum human life span. Anyone who says that doesn’t know what they are talking about. If you look back in history there is an apparent life span limit of about 120 or 122. But that would be like saying in 1870, there will always be pain during surgery or in 1900 that humans will never have powered flight.

What we’re talking now are technologies that can take humans far beyond what they naturally would get from just a good diet and exercise. So it’s impossible to extrapolate looking backwards. You need to extrapolate looking forward. And I can see the future from this vantage point with dozens of start-up companies and technologies that can make a significant difference in the human life span. And just one of these companies will have that effect. When we combine the technologies, I think that humans can live decades longer in a healthy way.

My father is part of an experiment in our family. He has been taking some of the molecules that we have shown to be safe, some molecules for over a decade. We’ll see how he goes, but he is 78 and he feels younger than he did when he was in his 30s. He’s climbing mountains. He’s whitewater rafting. He’s watching his friends become frail and die and he doesn’t feel any different than he did five decades ago.

WuXi: What are the societal implications of extending human life span 10, 20 or 30 years?

David Sinclair: There will be big changes to society, similar to what we went through in the 20th century. But on the whole we will be living in a better world that we would never go back to, similar to looking at the 19th century and their health.

We know what’s going to happen if we don’t do anything with health care. No nation can afford the health care trajectory. This is our best hope. In fact, I would argue, our only hope of making it through that health care crisis, which will slow down the world’s economy in the coming decades. The economic impact of increasing health span cannot be understated. It will raise global economic wealth by up to 10 percent in the short term. Long term it will allow countries to afford health care and education for all. The spare change can also be put towards protecting and restoring the environment.

The retirement age will likely have to be later in life. But people will be able to have second and third careers. My father just started a new career at age 78. If you’re given the choice of being sick or dead versus starting a new career, I think almost everybody, if they’re healthy, would take the new career option.

WuXi: How will extending life span relieve escalating health care costs as most of the spending now occurs near the end of life? Even if you live another 30 years, eventually your health will begin to decline?

David Sinclair: What we see in our studies with animals is that the longer the animals live, the faster they decline. That’s also true for humans. The longest lived humans have the least impact on the health care system. They die relatively quickly.

The problem with current medical research and the pharmaceutical approach is they study one disease and attempt to treat one disease at a time. What we’ve seen over the past 50 years, as a society we’ve been very effective in preventing heart disease, but not very effective at keeping the brain healthy. As a result we actually have an increase in dementia rather than a decrease; and we have people spending more percentage of their time in a dilapidated, decrepit state, which is extremely expensive and stressful for families.

The approach that the aging research community is taking is to say let’s not just keep one aspect of our body alive, not just one organ or one tissue, but let’s harness the body’s natural defenses against decay and disease and keep all of the organs healthy and young and resilient so that yes you can take a drug for your diabetes, but as a side effect you won’t get cancer and Alzheimer’s and by the way you’ll have a lot more energy and fitness, be able to go climb mountains and go white water rafting, things like my father does at 78.

WuXi: What are some ethical considerations in extending human life span?

David Sinclair: Some people worry that these drugs will be available only for the wealthy and that’s why I’ve pledged to make them available globally no matter how wealthy your nation is.

Another concern is that older people in their 70s and 80s should die to make way for the younger generation. My argument against that is try telling that to a healthy 78-year-old who’s productive and helping society. We know how to create jobs. There’s unlimited possibility for what humans can do to help each other and make the world a better place to live. There have been millions of jobs created in the past few years in the U.S. We have essentially full employment.

So it’s not a question of making way for the young. I would say that young people should want to have mentors who have seen 100 years of ups and downs. Wise mentors can help make sure that young people don’t make the same mistakes that they did.

Subscribe to WXPress

Receive our newsletter and information on upcoming events.