Delaying the Onset of Chronic Disease

Healthy Aging

Finding Holy Grail Geroprotectors

What are geroprotectors?

As we get older, our bodies become more susceptible to the onset of numerous diseases, which often determine our longevity. Traditionally, interventions have focused on a myriad of different drugs targeting different diseases after their onset. As to be expected when trying different weapons in the midst of a large battle, these approaches may or may not be effective.

Today, the world of geroscience is searching for broader, earlier stage approaches that protect us from becoming  susceptible to the onset of multiple diseases, before their onset. While this endeavor is a bold one, effective “geroprotectors” are expected to have a large, meaningful impact that stops (or at least delays) the onset of disease. Consider geroprotectors the ultimate whole body peacemakers that help us live healthier, longer.

In the Annals of the New York Academy of Sciences, DeVito et al. summarize the outcomes of a symposium on geroscience and geroprotectors. For this series, we’ll share the latest and greatest thoughts on how to discover holy grail geroprotectors that could meaningfully improve our healthspan and longevity.

Geroprotector Must-Haves

Among top-tier scientists searching for the ultimate geroprotector, they agree on a few must-haves:

• Must target the underpinnings of the aging process at the cellular level. If we want to have the broadest benefits to our whole body and mind, geroprotectors will need to shore up our cellular health. Not only should a geroprotector keep cells healthy, it should also help reverse aging in cells.
• Must result in clinically relevant changes. An intervention that changes telomere lengths or slows epigenetic clocks is, in concept, a way to slow aging. Unless the given intervention results in meaningful changes (aka healthier blood results, decreased pain, etc), however, it will go on the back-burner as a geroprotector.
• Must help prevent the onset of chronic diseases. In the ongoing clinical TAME trial evaluating metformin as a geroprotector, one of the key desired outcomes is the ability for metformin to prevent the onset of the following diseases in 65 to 80 year old people: myocardial infarction, stroke, congestive heart failure, cancer, dementia and, of course, death. If a geroprotector is helping our cells but not slowing the onset of chronic diseases, off the shelf it goes.

Geroprotector Must-Not-Haves

When looking for the perfect geroprotector, this list is just as important, right?

• Must not be toxic to cells. While this may seem obvious, many interventions that help can also hurt. Safety will be paramount to the optimal geroprotector.
• Must not be limited to short-term use. The mere nature of a geroprotector indicates that we will need to use this intervention over a long period of time. Thus, given this long-term relationship, the perfect geroprotector must be easy to use and remain beneficial over decades.

While much of the search for geroprotectors has focused on repurposing existing drugs (like metformin), many drugs have safety limitations that take them off the geroprotector table.