A Tour of Geroscience, Largely Focused on Unambitious Goals in the Treatment of Aging – Fight Aging!

Geroscience is a philosophy of development, suggesting that aging can be slowed and we should work towards means to do so. In practice, geroscience is, more or less, the the name given to that part of the research and development community that aims to produce means to alter metabolism to modestly slow aging. It is best represented by the development of supplements and repurposing of very well studied drugs, near all of which produce smaller benefits to long-term heath than regular moderate exercise, and none of which can match the benefits provided by the practice of calorie restriction. It is entirely unambitious. This lack of ambition is one response to a regulatory environment that makes it very challenging and very expensive to produce entirely novel therapies that are capable of achieving sizable benefits. Many groups simply retreat to forms of development that are easier, even though the benefits will be small.

The current popularity of geroscience will be nothing more than a footnote in the history of aging research if it continues to produce supplement companies and interventions that achieve very little in the grand scheme of things. If the primary output of the Buck Institute for Research on Aging is supplement companies, as seems to be increasingly the case, then the Buck Institute for Research on Aging is irrelevant to the goal of treating aging as a medical condition. The research community knows more than enough about the causes of aging to produce therapies that are capable of far more than simply tweaking the operation of metabolism to age a little bit more slowly. We want more programs aimed at repair of the molecular damage that causes aging, and thus rejuvenation, and fewer programs aimed at characterizing metabolic changes that cannot even in principle achieve a greater slowing of aging than is produced by good lifestyle choices.

Is aging without illness possible?

Each morning after breakfast, Scott Broadbent takes a plastic bottle from the refrigerator in his home in Alameda, Calif., pops the top, and drinks the contents, 2.5 ounces of milky liquid. The bottle might contain ketone ester, a supplement meant to help the body burn fat instead of carbohydrates. Researchers are now testing whether it might also slow the aging process. Or Broadbent might instead be getting a placebo. He is part of a clinical trial at the nearby Buck Institute for Research on Aging to assess the supplement’s safety and side effects in older adults.

A retired chemist who used to work for pharmaceutical companies, Broadbent is 70 and in excellent health today, but he worries about the future. He’s not necessarily afraid of dying, but he doesn’t want to be sick and in pain as he grows older. Some scientists think there’s a better way. These researchers – part of a burgeoning field called “geroscience” – aren’t seeking immortality. The focus is much more pragmatic: By addressing the root causes of aging, they hope to stave off the disability and diseases that can make old age so miserable. They want to help people feel healthy for longer, compressing the years of illness that often accompany old age into a much shorter time frame.

Though there are no proven therapies for people yet, geroscientists are eyeing several compounds that can slow the aging process, at least in worms, fruit flies, and mice. Some have already been tested in humans, and many more clinical trials are under way. Perhaps the best studied is rapamycin, a compound first discovered in a soil sample collected in 1964 from Rapa Nui, or Easter Island. Today, people who receive organ transplants take the drug to help keep their immune systems from rejecting the foreign tissue. But rapamycin also prolongs life in yeast, flies, and mice. And it’s being tested in people in clinical trials. How it counters aging isn’t entirely clear. The drug inhibits a protein complex called mechanistic target of rapamycin, mTOR for short, which plays a role in cell growth and protein synthesis. This inhibition appears to have wide-ranging effects, including reducing inflammation, clearing old and damaged cells, and altering cellular metabolism – some of the key processes that researchers think are to blame for the aging process.

Diet is also known to profoundly affect the aging process. Studies have found that the low-carb ketogenic diet, for example, can help mice live longer. But restrictive diets can be hard to follow and have side effects. Broadbent followed the ketogenic diet for a month or so, but his cholesterol levels went dramatically up. Ketone ester, the compound Broadbent might be downing each morning for the Buck Institute’s clinical trial, may mimic the longevity benefits of such diets. When the body runs out of glucose to use for energy, the liver creates another source by converting fat into molecules called ketone bodies. These compounds are more than just fuel. They help regulate inflammation and control other cellular processes, many of them involved in the aging process. Drinking ketone esters, which quickly break down, is a way to deliver the ketone bodies without the diet.