Part of a series.
A pill to end aging.
Is there or could there be such a pill? Some researchers think so.
Many believe that rather than attack the causes and treatment of chronic illnesses one by one, it would be better to understand the biology of aging and from that learn how to slow the process and hence prevent or delay the onset of various chronic illnesses.
Today, the lifespan for a male is about 76 years and a female 81 years. Most people die of a chronic illness such as heart disease, cancer, stroke, diabetes or Alzheimer’s. These are diseases that become increasingly frequent during aging and so are termed “age prevalent diseases.” It is clear that many of these can be prevented or at least delayed with lifestyle modifications. Most important are physical exercise, good nutrition, no tobacco and reduced stress. Of course, a pill would be simpler. Too many people are not willing to accept lifestyle modifications whereas they would happily take a daily pill!
Alternatively, however, it may be that most chronic illnesses are not age-induced but lifestyle caused, they just take a long time to manifest and therefore become age-prevalent diseases. In that case, a pill might not prevent or delay them although it might extend lifespan.
For any drug to be considered effective and valuable it will need to be easy to take (e.g., pill), effective even if not initiated until adulthood and, very importantly, have few if any significant side effects. A tall order for sure!
No drug has been found that will stop the aging process, only slow it down, perhaps considerably. As such, some scientists suggest that anti-aging drugs might be able to extend life to about 120 years but probably not much more.
Here are some examples of drugs being considered.
Vitamins and supplements
One of the theories about the cause of aging is that free radicals cause damage over the years. Hence, antioxidants would be valuable. These include vitamins C and E, coenzyme Q and others. However, no controlled clinical trials have been developed nor will they because the over the counter drugs are relatively inexpensive and the costs of a trial would be high.
There are enzymes in cells called sirtuins that control a variety of biologic pathways related to the aging process. They do this apparently by affecting the activity of mitochondria, the energy factories of the cell. Resveratrol is one of many compounds called sirtuin-activating compounds or STACS that can modify the activity of sirtuins. In the 1990’s Leonard Guarente and two colleagues at MIT found that yeasts that had an extra copy of a gene for a sirtuin gene lived longer. About a decade ago, David Sinclair at Harvard found that resveratrol stimulated or activated sirtuins. There was great enthusiasm about resveratrol. This is the substance found in red wine that when given in high doses to obese mice led to much longer lives. Venture capital was brought in; magazine and news articles were written. Many supplements containing resveratrol appeared at the local health food store. But to date, there have been no clinical trials.
Metformin has been on the market for more than fifty years as a drug to treat diabetes. It is well known to have relatively few side effects.
When tested in the roundworm, C. elegans, the worms remained healthy and aged more slowly. Studies in mice showed that they lived nearly 40 percent longer than normal.
So it was interesting that a review of a U.K. Registry of 180,000 people showed that individuals with diabetes mellitus who took metformin lived longer than those treated with another diabetes drug, a sulfonylurea. Of course, there may have been variations unappreciated in the two groups leading their doctors to prescribe one drug versus another. Still, the difference in lifespan was unexpected and intriguing. Further, the older diabetic patients on metformin also lived longer than older non-diabetic individuals. The groups might not have been similar but on the surface, at least, you might expect those with diabetes to die sooner — not later — than those with diabetes mellitus.
Why should metformin be effective? No one really knows for sure, but apparently, it reduces toxic compounds from aging cells.
An FDA-approved controlled clinical trial will begin in 2017 testing the hypothesis that metformin versus placebo will lengthen life. And the hypothesis also raises the question of whether slowing the aging process will also delay or prevent age prevalent disease. Termed Targeting Aging with Metformin, or TAME, the trial is recruiting individuals between ages 70 and 80. Various scientists are saying that metformin treatment, should the trial be positive, would prove be one of the most important therapeutic advances in decades.
Time will tell whether metformin has a beneficial effect and, if so, whether it is an effect that is clinically significant. Further, it should determine if slowing the aging process, if that happens, will also slow the onset of chronic illnesses.
Another drug, rapamycin, also increases lifespan in mice and rats. Rapamycin has been used to prevent rejection in human transplant recipients for the past two decades. Given its side effect profile, there is appropriate anxiety about using rapamycin in humans, but some clinical trials are underway with companion dogs. Dogs develop many of the same age-prevalent diseases as humans but do so over a much shorter lifetime. Hence, rapamycin is being evaluated for its effect on lifespan, cardiac function and perhaps cancer onset and immune function.
Drug companies have not put a lot of interest into anti-aging drugs for three possible reasons. First, the knowledge base upon which to develop such drugs has just not been available. Second, natural compounds, such as antioxidants and generic drugs like metformin, don’t offer much opportunity for profit. Third, it has been unclear if the FDA would approve an indication labeled “anti-aging.” But this is all rapidly changing. The knowledge base is growing. Patentable drugs look increasingly promising. And the FDA has now given the green light for the metformin trial.
The business opportunities are obviously great. Conceptually, firms see that if anti-aging compounds also prevent age-prevalent diseases, then they can sell them effectively as drugs to reduce total health care expenses.
Before we get too excited about a “pill to delay aging,” let us remember that sound nutrition, plenty of exercise, no tobacco and reduced stress can and do have a very measurable impact. Of course, it takes commitment and time along with persistence, but it does work and is certainly worth the effort expended.
Stephen C. Schimpff is a quasi-retired internist, professor of medicine and public policy, former CEO, University of Maryland Medical Center, and senior advisor, Sage Growth Partners. He is the author of Fixing the Primary Care Crisis: Reclaiming the Patient-Doctor Relationship and Returning Healthcare Decisions to You and Your Doctor.
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