We’re on the verge of changing how we will age - Dr. Verdin

Interview with Dr. Eric Verdin - President and chief executive officer of the Buck Institute for Research on Aging.

You recently joined the Scientific Advisory Board of Amazentis, the Swiss life science company behind Mitopure and Timeline, why?

Amazentis started with a basic discovery in the laboratory and is now bringing it to the clinic for use in humans. I am really excited by the focus that Amazentis has placed on testing the efficacy of their product in the clinic. By conducting these hard experiments, they are making a progressively stronger case that supplementation with urolithin A could be a game-changer for human health and longevity.

What drew you to studying longevity and lifespan? Tell our followers a little about the journey that ultimately led you to the Buck Institute.

I was born in Belgium and received my Doctorate of Medicine there from the University of Liege. Being interested in biomedical research, I came to the United States for continued training at Harvard Medical School. While the science of molecular aging is relatively new, less than 20 years old, the US really is at the forefront of this research which is how I came to stay here.

My interest in aging really came from a breakthrough we had while we were studying the epigenetic regulation of HIV transcription. We discovered a family of proteins that play a critical role in aging. These proteins are sirtuins. My colleague Leonard Guarente at MIT in Boston identified sirtuins in an aging model in yeast, and from there, we looked at mouse and human genomes to see if there were similar proteins. We’ve focusing for the past twenty years about understanding their role in aging.

Given the state of scientific understanding, what are reasonable expectations for “healthspan” for people in middle age today? How about expectations for young people?

There’s a lot of hope and a lot of excitement that we’re on the verge of really changing the way we age and the perception of how we will age. Our goal as longevity researchers is to transform everyone into a centenarian so that everyone could live to 90-95 in good health.

Many of our followers keep up to date on the latest findings in longevity science and are familiar with sirtuins, NAD+, and other compounds that you are currently studying. For those who may be unfamiliar with these terms, do you have a simple way to explain their importance in health and aging that a wider audience could understand?

We can think of proteins as tools that our cells use to do everything we do, and sirtuins are a family of signaling proteins that are involved in many metabolic responses. They influence things like inflammation, DNA repair, and aging. They appear to be inducing a protective response in our cells. So when these proteins become activated, our cells become resistant to stresses and the aging process.

Some sirtuins are dependent on nicotinamide adenine dinucleotide+ (NAD+) which is a coenzyme essential to metabolism and cellular energy production. As we age, NAD+ levels decline and we experience a loss of sirtuin activity. We are currently exploring the role these proteins and metabolites have in slowing the aging process.

Decline in mitochondrial health is another hallmark of aging, which is why I am so interested in the research by professor Johan Auwerx and the team at Amazentis. They discovered that this compound called Urolithin A (UA) activates mitophagy, an essential mitochondrial repair pathway that clears away damaged mitochondria as we age.

Can you help our community understand the basic principles of bioenergetics and mitochondrial function and how that plays a role in the development of age-related disease?

Bioenergetics is the study of how our cells transform energy. Being the energy center of our cells, the mitochondria play a crucial role here. Mitochondria are involved in the production of ATP and healthy mitochondrial function has been linked to improved physiological benefits such as improved muscle strength, which is vital as we age. Because the mitochondria produce reactive oxygen species as part of their metabolic processes to create energy, they are susceptible to a high amount of oxidative stress and DNA damage, which we believe plays a significant role in the aging process.

Ultimately, the aging process is the slow accumulation of cellular damage. Damage can occur in the form of DNA mutations or misfolding of proteins, which causes the proteins to lose their activity.

The body has a number of monitoring systems in our cells that help to ensure that everything is functioning correctly and which eliminate or repair damaged cells. Our repair systems keep us healthy and performing for most of our life. Yet, at some point, that changes. We currently believe that there is either the accumulation of irreversible damage or a loss of the repair mechanism that occurs at some point in our lives, leading to age-related disease.

Concerning cellular aging, what research is looking most promising at this moment in time? What are you most excited about continuing to study and uncover?

Over the last five years, we have learned a lot about compounds generated during the fasting process and their role in aging. Fasting causes us to utilize stored fat for fuel instead of the carbohydrates that we eat. When this happens, fats go into our liver and are transformed into ketone bodies. These ketone bodies can then be used by the heart and the brain for energy.

We are learning a lot about how these ketone bodies work in the aging process. One way is they appear to protect us against oxidative stress, which offers protection against the manifestations of aging. We are currently trying to generate new ketone body-like substances that we will be able to ingest. These compounds would then mimic the effects of fasting and help protect against age-related damage while still eating a normal diet.

Additionally, the research being conducted on Urolithin A shows much promise in supporting mitophagy and supporting healthspan. The Buck institute first became aware of UA’s potential from research conducted in Johan Auwerx’s lab published in Nature Medicine looking at how the compound UA increased the lifespan of c. elegans and improved muscle function of mice. This research is very intriguing to us and what we are studying this molecule at the Buck. Taking it one step further, we were especially excited by the Amazentis trial, which was done in humans and replicated the findings that have been done in animal models.

Based on the available evidence today, what are some novel things the general public should be incorporating into their lifestyle to help promote healthy aging. What are some practices you do?

The two major things someone can do to help promote healthy aging are to exercise and modify one’s diet.

Eating vegetables is one way to induce a protective response. Plants have developed a number of chemicals that help protect them from being eaten, and research suggests that this confers mild stress onto us when we consume them which is thought to generate an adaptative response against other cellular stresses that contribute to aging.

Fasting and caloric restriction is another way to safely stress the body. There are several ways to fast but I favor time-restricted feeding where an individual abstains from eating anywhere from 12-16 hours every day. There is still much to learn about which type of fasting ultimately offers the most benefit, but there is growing evidence that any form of fasting induces a protective response.

Looking back at the last decade or so, what are some of the biggest breakthroughs that have been discovered in regards to cellular aging? As you look forward into the next decade or so, what do you anticipate will be the areas of greatest advance?

Over the last decade, we have started to take longevity research very seriously and, as a result, have discovered many precise molecular mechanisms that are involved in the aging process. It feels a bit like we are still pioneers in this field, and the last five years especially have led to a number of promising developments. Additionally, we are shifting our focus from lifespan to focusing on healthspan which is living not just longer, but more healthfully, which is what we ultimately all want.

One thing we’ve come to understand is that much of what happens to us as we age is not actually based on genetics but rather our lifestyle. A recent study has found that only seven percent of the aging process is due to our genes which leaves a lot of room for our habits and environment to dictate our healthspan. It is exciting to know that we can take aging into our own hands and be active players in how we age.

One thing that I’m hopeful that we will see in the near future is creating models where we can study longevity in humans rather than animal models. As you can imagine, this is a challenge with the human lifespan being much longer than worms, mice, or even primates, so both study design and the high cost of these long-term trials need to be addressed. As we identify functional markers of aging in the blood, we will be able to create predictive models of aging in humans that do not take decades of following the study participants.