Can Aging Be Reversed?

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By Jad G. Sfeir, MD, FACP
Faces of young and elderly woman

Memory decline, arthritis, heart disease, hearing loss, diabetes, frailty, osteoporosis, decreased kidney function, cancer…as we grow older, it seems our bodies accumulate more and more ailments and diseases.

Aging is a process that seems to be universal, as all species – and all organisms within a species – experience it. It is also progressive and intrinsic, meaning aging is naturally built into our bodies, and we have no control regarding when and how it starts or how quickly it progresses.

In fact, cells in the body start aging as soon as we are born. And by our late 20s, many organs in the body start deteriorating and lose their full functioning potential. Plus, the older we get, the more we become frail, meaning that our ability to recover from injuries or stressful health-related events is diminished.

But is aging irreversible? The short answer, surprisingly, is: not necessarily!

We know that some species such as jellyfish can reverse the aging process and go through periods of growth and degrowth. Unlike the jellyfish, our bodies do not have the ability to reverse or stop this process. The aging process in humans leads to changes in the metabolism of our organs that accumulate over time and cause a number of chronic diseases such as those mentioned above. However, recent advances in medicine are leading to insights about how aging develops and, even more important, how it can be delayed or slowed down.

So How Can You Give Your Internal Organs a “Facelift”?

Rather than aiming to live longer, perhaps the goal should be to live healthier. It is an important distinction that researchers in the field make between “lifespan,” which is how many years we live, and “healthspan,” meaning the length of time we live in good health. Unlike Meryl Streep and Goldie Hawn’s characters tried to do in the film “Death Becomes Her,” we aim to “add life to years rather than years to life,” as renowned aging researcher Dr. James Kirkland said.

Many factors contribute to how long and how healthy we live. Our genetic makeup is probably the most important of these factors. Jeannette Calment, from Arles in southern France, has the longest confirmed lifespan of a human, having survived all members of her long-living family. She died in 1997 at the age of 122 years and 164 days. She must have good genes, one would say! She probably did. In fact, hundreds of genes have been discovered that can impact longevity. But there are additional factors such as our diet and the environment in which we live that also impacts longevity.

Take, for example, the small Italian town of Acciaroli in the Mediterranean basin: It has a population of 2,000 people of whom about 300 are 100 years of age or older and are free from dementia or heart disease. Scientists proposed many theories to explain this phenomenon, including the seaside weather in that town and the (now-famous) Mediterranean diet. Or maybe the Mediterranean Sea is feeding into a fountain of youth in Acciaroli!

How Can We Get to the Fountain of Youth?

Until now, chronic diseases associated with aging have been treated individually, using a one-disease, one-drug-class approach. For example, bisphosphonates (such as Fosamax, Actonel, Boniva) are used to treat osteoporosis, antihyperglycemic agents (such as metformin, glimepiride, sitagliptin and empaglifozin) are used for diabetes, and so forth. This leads to an increasingly large number of drugs taken simultaneously by one person who requires treatment of multiple conditions (called polypharmacy), with an increased chance for drug interactions and potential drug side effects.

But what if we find a common pathway to all these aging-associated chronic conditions and diseases that can be targeted with a single drug? Multiple research studies around the world have identified the fundamental process of aging to be behind a number of changes in our bodies, such as inflammation, poor metabolism, and damage to the cells and DNA that eventually lead to development of many age-related diseases. By targeting this common process, we can theoretically slow or prevent many of these diseases with one single drug.

"It is an important distinction that researchers in the field make between “lifespan,” which is how many years we live, and “healthspan,” meaning the length of time we live in good health."

This common pathway is what is known as “cell senescence.” It means that, as we grow older, the cells in our body accumulate damage over time and retire from their normal function; they don’t die, but rather become “senescent cells,” just like a zombie, some would say. They accumulate in many organs and tissues in the body and now have a new role: releasing a number of chemicals, known as SASP (Senescence Associated Secretory Phenotype), that can cause a number of metabolic changes, such as resistance to insulin that eventually leads to diabetes and bone loss that eventually leads to osteoporosis.

It’s important to realize that these senescent cells are not all bad. They are important in healing wounds. Also, if the cells that accumulate damage over time don’t retire, they may turn into cancer! This means that the best way to improve the healthspan is to let them retire and then either kill them or block the release of the SASP chemicals. That way you prevent the damaged cells from turning into cancer, but at the same time prevent them from causing chronic diseases.

Over a dozen senolytic drugs (from the words “senescence” and “lytic,” which means destroying) have been discovered and, when tested in mice, have proven to be effective. When old mice received these drugs, their number of senescent cells went down and the amount of SASP they release decreased. After treatment with these drugs, their bone strength improved, their cardiovascular function and insulin sensitivity – how well the body responds to the effects of insulin – also improved and they had fewer symptoms of frailty.

As the drugs that clear the senescent cells, senolytic drugs work using a “hit-and-run” approach: They are given once to kill the senescent cells, and then the tissue is allowed to rejuvenate over several weeks before another dose of the drug is given. Senolytic drugs do not affect normal healthy cells.

These drugs have the potential of changing medicine as we know it today. However, it will be some time before they make it to the market. What works in mice does not always work in humans, plus there might be side effects in humans that have not been seen in mice. So, although experiments in humans are already underway, these drugs are not ready for prime time yet.

Another area where senolytics can be useful is preventing side effects related to radiation therapy and chemotherapy – drugs used to treat cancer and HIV. While radiation kills cancer cells, it also causes damage to normal, healthy cells and increases the number of senescent cells in tissues. Using senolytic drugs can prevent this. For instance, in mice, if you treat one leg with enough radiation, after three months, the mouse has trouble walking. If you give a single dose of senolytic drugs, they are able to walk quite well.

At What Cost?

Senolytics have to go through the clinical trials process. The first step in human experiments is to test the safety of these drugs. Researchers will then have to identify the best dose and frequency that will give the anti-aging benefit while minimizing the number of side effects such as poor wound healing. Next, the drugs will go through the U.S. Food and Drug Administration (FDA) approval process. Once approved, they will be available for widespread use.

Some scientists expect that these drugs will cost as much as some chemotherapy agents, which can be costly. On the other hand, they will theoretically decrease the number of hospitalizations. The overall savings in healthcare will possibly offset the cost of these drugs by a long shot.

There’s no doubt exciting developments in this area of science are underway, so be on the alert to new information and developments as researchers explore how to live well in our “senior days.”