by Patrick Cox
October 21, 2015
John Mauldin and I spent the day at “the Buck” earlier this week at the invitation of Brian K. Kennedy, Ph.D., the president and CEO of the Buck Institute for Research on Aging. The Buck is the world’s first major scientific research institution dedicated to solving the problems of aging. This includes, to make things clear, the development of anti-aging biotechnologies. Founded in 1999, the institute currently employs about 140 Ph.D.s as well as more than 100 technicians and support staff in 22 labs dedicated to different challenges.
We spoke at length with Kennedy, who has run the Buck Institute for five years, but were also shown the facility designed by renowned architect I.M. Pei, who came out of retirement due to his support for the institute’s mission.
Expecting a tour led by an intern or public relations person, I was surprised and flattered that Mary McEachron, the chief administrative officer and general counsel of the institute, acted as guide and historian. Without McEachron, the Buck Institute might not exist today. She was the attorney most responsible for defending the will of Beryl Hamilton Buck, who wanted to fund an anti-aging institute in northern Marin County, California. The San Francisco Foundation sued to break the Buck trust, arguing that the money should be spent elsewhere because Marin County is one of the wealthier counties in America.
In a court battle that spanned years, McEachron successfully argued that the scientific mission of the Buck Institute—to solve the problems of aging—would benefit not only San Francisco but the rest of the world as well. I find it somewhat remarkable that anyone could even argue with that premise, but it was a somewhat different world in the ‘80s when the suit was in court. In those days, the notion that science might be able add a decade or two of healthy years to our lives was pure science fiction.
The Specter of Overpopulation
Despite the fact that life expectancy at the time was increasing about a month per year, nobody expected the development of real exponential improvements in health spans before the arrival of commuter jetpacks and robotic maids. Additionally, the ‘80s were a time of fear spread by scientists from leading universities and the UN, of looming catastrophe caused by overpopulation and resource depletion.
Many believed that significantly longer lives, if they ever arrived, would only hasten doomsday.
Now, of course, we know that fertility rates were already headed downward in the ‘80s, apparently a side effect of longer lives and higher living standards. Today, global birthrates are well below replacement rate and still falling. Instead of peak oil, we’ve hit peak babies as well as peak workers.
To the extent that world population is still increasing, it’s only because life spans are increasing quite rapidly, particularly in formerly undeveloped parts of the world. People aren’t dying as soon as they used to, so total population figures will grow for a while before turning downward.
We now face a real threat in the 21st century, unlike so many past Chicken Little panics. It is aging.
The Solution: Increasing Health Spans
Though every one of us faces this problem individually, the real issue is the societal and economic impact of an increasingly older population, leading to exponentially growing healthcare and retirement costs due to age-related diseases.
These age-related diseases are forcing retirements and draining treasuries worldwide. The US government already is borrowing 30 cents of every dollar it spends, which happens to be almost the exact percentage of the budget that flows to the aged in the form of Social Security, Medicare, and other transfer payments. The trends that have created this problem, however, are accelerating as the population of transfer payment recipients/beneficiaries gets bigger due to increased life spans. At the same time, the number of younger contributors/payers into the system is shrinking along with birth rates.
This is why life extension in the narrowly defined sense is not the answer. In fact, it is in many ways the problem. Tacking extra years onto the end of life for a person who is already ailing and feeble only increases costs and suffering. The only real solution is anti-aging biotechnologies that will extend health spans and careers so that each generation can pay its own way instead of sending the bill to the next.
Part of the reason I enjoyed visiting Brian Kennedy and the Buck so much was that I was surrounded by so many brilliant people who not only understand how grave this threat is to our system, but who also understand that it is solvable. Kennedy himself spends a considerable part of his time explaining the economics of aging to the public.
In the last four or five years, he told us, the community of scientists who research aging has become convinced that we can significantly increase health spans. The consensus among top researchers is that we have the ability to delay the processes that cause age-related diseases. Meanwhile, progress educating the public about this good news is slower, but it is happening.
For obvious humanitarian reasons, I want everybody to understand right now that our most serious problems are solvable. As a financial analyst, however, I realize that this disconnect between reality and public perception is the basis for the biggest financial opportunities of our era.
Just as energy can be generated from two systems with different thermal or charge states, transformational investors can profit from the investment communities’ failure to grasp these enormous but unrecognized forces. Yes, yes, I’m a capitalist… but the people who fund the technologies that solve our biggest problems more than deserve to be rewarded.
Obstacles to Progress
Kennedy agrees that society will eventually recognize that anti-aging therapeutics are necessary. This is because the problems of aging will worsen until an irate public forces us to solve them. Right now, however, our institutions are decades behind the science.
Kennedy pointed out, for example, that NIH funding for scientific research has flatlined and the odds of getting grant money for truly important research have fallen badly. Ironically, this is largely due to budgetary pressures created by societal aging that are straining budgets around the world.
Lest you decide that increasing the NIH budget is the solution, Kennedy cites calculations that less than 1% of NIH grants support research into the aging pathways. I love pure science as much as anybody, but we might do better prioritizing research funding for the problems that threaten our health, economy, and our children’s future.
Another enormous problem is that the FDA’s approval processes were created before the biotech revolution gave us insight into the molecular pathways and mechanisms targeted by drug candidates. As a result, they are unnecessarily slow and expensive.
This is tragic because, as Kennedy points out, it will be easier to target aging than to reverse the diseases caused by aging. It’s also much, much cheaper.
The benefits of anti-aging therapies are twofold. Not only are they far less expensive than disease treatments, they keep people healthier longer so they are able to move out of the recipient column into the contributor column. So the balance sheet is improved from both sides.
A primary focus of the Buck Institute has been research into rapamycin, the antifungal compound produced by bacteria found on Easter Island. Kennedy pointed out that the ability to impart life- and health-extending benefits—even late in life—has come as a surprise even to the research community. This makes sense because people tend to assume that aging irreversibly damages cells and cellular processes. If this were the case, it would mean that anti-aging interventions late in life would provide little benefit to animals, including humans.
That isn’t the case, though. Diseases do not seem to be caused by physical damage to the body brought about by aging, as was previously believed. Rather, many of the complex genetic systems of the body are thrown out of whack as we age, causing impaired functionality that leads to disease. Therefore, a compound that restores biological systems to a healthier state will have a major impact on health spans for older as well as younger people.
In rodent studies, animals the equivalent of 65 human years old received rapamycin, resulting in major improvements in health as well as a 15% improvement in life spans. The videos of the mice treated with rapamycin compared to normal mice are striking in contrast. Somewhat greater benefits accrued if therapy began earlier, but the majority of the benefits from anti-aging therapies can be delivered rather late in life.
If this model holds for people (and I think it has to), it means 65-year-olds could experience major improvements in apparent age and increase their life expectancies from 80 to 92 via some form of rapamycin, which reduces the side effects that accompany the form of the molecule widely used to prevent organ transplant rejection. Even if it were only a 10-year increase in health and life spans, most of us would be willing to pay a great deal for that benefit—especially because it would cost much less than treating the diseases it prevents.
Though biogerontologists and demographers now understand this, most people do not. When I speak to older people about the anti-aging strategies that are being impeded by regulatory burdens, the typical attitude I see is that it’s already too late for them to benefit from these discoveries. This is entirely wrong. Even if you’re quite old, you could benefit enormously from these strategies.
Another common misperception that Kennedy pointed out to John and me is that anti-aging research is going to benefit only the very rich. Once he said this, I realized how often I had encountered this attitude. In fact, rapamycin, metformin, and several other extremely promising anti-aging candidates are not terribly expensive to manufacture.
The costs imposed by our regulatory system will raise prices somewhat, but anti-aging therapies are going to reduce healthcare costs so much, insurance companies will be happy to pay for them once they are approved. The real reason to support anti-aging efforts, Kennedy points out, is to avoid financial disaster.
Though Kennedy has focused a great deal on rapamycin, he has also studied metformin. He discussed efforts by his friend Dr. Nir Barzilai to get FDA approval for clinical trials that would demonstrate the life-extending benefits of this widely used diabetes drug.
Barzilai is director of the Institute for Aging Research at the Albert Einstein College of Medicine and the director of the Paul F. Glenn Center for the Biology of Human Aging Research. If Barzilai is allowed to show in clinical trials that the markers of aging have been improved, it could open up the path for other compounds such as analogs of rapamycin, the NAD⁺ enhancers, and anatabine citrate to seek approval as anti-aging compounds.
The “Age” Age
This raises the obvious question about the various compounds with proven anti-aging effects in animals that are mirrored by biochemical improvements in humans. Kennedy suggested that, because they work on different pathways, these therapies could be synergistic. Besides variations of the rapamycin molecule and metformin, he volunteered that we could see these benefits from the compounds that restore mitochondrial function, which I’ve discussed here at length.
Kennedy also brought up Valter Longo’s fasting mimicking diet, which I’ve written about extensively and enthusiastically. Kennedy has collaborated with Longo on much of his research, and they’ve co-authored peer-reviewed journal articles. Kennedy’s work, not surprisingly, has appeared in top journals such as Cell, Nature, Science, Genes & Development, and Proceedings of the National Academy of Sciences of the United States of America (PNAS).
I think it’s incredibly meaningful that even the most careful scientists such as Brian Kennedy and the researchers who work at the Buck Institute now believe science has the ability to quickly extend health spans enough to solve our demographic and financial challenges. You’ve undoubtedly read or heard of an instance where somebody labels the current era with one description or another. “This is the age of (fill in the blank).” Kennedy gets it right, however, when he says, “This is the Age age.”
If you’d like to learn more about the change in scientific attitudes about aging and feel like spending a few dollars to do so, I recommend “Geroscience: Linking Aging to Chronic Disease” in the journal Cell.
The summary couldn’t be plainer: “Mammalian aging can be delayed with genetic, dietary, and pharmacologic approaches. Given that the elderly population is dramatically increasing and that aging is the greatest risk factor for a majority of chronic diseases driving both morbidity and mortality, it is critical to expand geroscience research directed at extending human healthspan.”
Note, by the way, that this article is co-authored by Kennedy’s friend Claudio Franceschi, who coined the term inflammaging. If you’ve been following my work, you know how much I admire Franceschi’s work.
If you’re interested in helping fund the Buck Institute’s work, you can learn more about it at this link. There’s a link to one of Kennedy’s TedX videos on the front page of the site, which is also available through YouTube.
Originally published at Transformational Technologies.