A Treatment for Aging? Revolutionary New Science Could Help Us Live Healthier and Longer.

By Joe DeSantis The United States faces a human and financial crisis of chronic illness. Every year, one-fifth of our economy – about $3.7 trillion – is lost to chronic diseases such as heart disease, dementia, diabetes, and cancer. This includes the cost of treating the diseases ($2.1 trillion) and the lost economic output from people being sick and being caregivers. These costs are projected to increase even higher as the number of Americans with chronic illness grows from 157 million to 200 million by 2050. In part, these daunting figures are a byproduct of our success in treating these diseases. For instance, in 2018, the US experienced the largest one year drop in cancer mortality in history. This follows the previous largest one year drop in 2017. Overall, since 1991, the cancer death rate has fallen by 31 percent. Deaths from heart disease have also experienced an extraordinary decline over the past several decades. Roughly one-third the number of Americans die annually from heart disease today than in the 1970s. The challenge is that as we improve survival rates with disease, people live longer, which increases their risk of developing other diseases. In fact, aging is the No. 1 risk factor for disease. The National Council on Aging estimates that not only do 80 percent of Americans over 65 have one chronic condition, 68 percent have two or more. The US Centers for Disease Control and Prevention has a narrower definition of chronic disease, but even it shows that 56 percent of all Americans over 65 have two or more chronic conditions. This whack-a-mole challenge in treating chronic disease as we age, and the increasing expense of doing so, has led to a renewed focus on prevention in health care. Doctors and health plans are paying more attention to the lifestyle factors that put us at higher risk of chronic illness and seeking to help their patients and customers live healthier lives. This is a welcome development, but we should be realistic about how difficult it will be to make significant improvements in chronic disease at a population level simply by encouraging healthier lifestyles. While we have had success in reducing smoking in America, it was due to a massive, society-wide effort that was given unusual urgency by the fact that one person’s smoking puts others around them at risk. The same cannot be said for lack of exercise. In fact, most of the trends of modern life make healthy living harder, not easier. Getting people to be more active, eat healthier, and sleep better is swimming against the tide. Fortunately, a new scientific field has emerged that could significantly expand our toolbox to prevent chronic disease. The key insight of this new science is the close connection between risk for developing chronic illness and aging. Geroscience asks: What if chronic diseases are better understood as symptoms of the underlying condition of aging? What if by treating aging, we could prevent or significantly delay the onset of a whole constellation of chronic diseases? The idea of treating aging seems confusing until you understand that what these scientists mean by aging is not simply adding years to your life. They are referring to a process of growing dysfunction at the cellular level in organisms that increases the risk of disease. Geroscientists have identified nine “hallmarks of aging” in humans that negatively reinforce one another, causing a downward spiral in health. Treatments for aging would target one or more of these pathways to maintain healthy cell function for longer, thus preventing disease. Geroscience is more than a theory. Scientists have used a variety of techniques from small molecules to gene therapies to target aging pathways in mice. The results of those experiments have been mice that don’t just live longer, but live healthier, with much lower incidences of age-related diseases during their lives. As exciting as these developments are, it is always a big leap to get treatments that work in mice to be effective in humans. But this challenge is particularly difficult for therapies to treat aging. Our entire regulatory framework for pharmaceuticals is based on the idea of treating diseases after they occur, not preventing them. In order for the US Food and Drug Administration to approve a treatment, a pharmaceutical company must show that it is safe and it achieves a clinically meaningful endpoint in how a patient “feels, functions, or survives.” It is not clear how to apply that standard if a patient starts off healthy. At the least, it would require clinical trials that last years and involve thousands of people to show a lower rate of onset of age-related chronic illnesses in the treated group compared to controls. These sorts of trials would be expensive. For this reason, most, if not all, of the clinical trials being run right now in humans that target aging pathways are for the purpose of treating diseases, not preventing them. This is certainly worthwhile, but it is not actually harnessing the truly revolutionary nature of this approach. The bet these companies are taking is that if they can show that this concept of targeting aging pathways can help treat disease, then it will create a “foot in the door” to using the same treatments to prevent them. One solution is to allow the use of surrogate biomarkers based on the identified nine hallmarks of aging to be used as endpoints in clinical trials. Geroscientists have created “aging clocks” that use some of these hallmarks to measure your “real age.” Treatments could be measured effective if they slow, stop, or even reverse patients’ aging clocks. (One small clinical study attempting to regrow the thymus gland with human growth hormone had the unexpected side effect of decreasing participants’ aging clocks by 2.5 years.) There is some precedent for this. For instance, treatments that reduce tumor size are assumed to be making an improvement because tumor size is recognized as a marker for cancer progression, and thus survival time. As more scientists, doctors and regulators are educated about aging biomarkers and their relationship to developing chronic diseases, a similar model could be adopted for aging therapies. Of course, discussing an idea like treating aging leads one to wonder: Could we eventually live forever, and in good health? Maybe, but even the most optimistic of scientists in the field say that we are far away from that point. It makes the most sense to focus on the potential of what we know now – using therapies that prevent chronic disease instead of waiting to treat them once they appear. This is a revolution that could be the key to solving America’s crisis of chronic illness. To learn more, listen to Newt’s interviews with Dr. David Sinclair and Dr. Nir Barzilai on his podcast and stay tuned for more news on how you can get involved in helping this new field of science make the transition from the lab to the clinic. Newt hosts monthly virtual events in which he discusses news of the day and why it matters to you and your community. These Newt Live events are your opportunity to communicate directly with Newt. We hope you will join us next time and let Newt answer your questions and provide his insight on the issues that concern you most. JOIN TODAY to be a part of this special event and receive a BONUS GIFT. Click here to join Newt’s Inner Circle.

INNER CIRCLE MEMBER CONTENT

Did you watch the debate between Governors Newsom and DeSantis?