Research & Discovery > Guiding Bodies Into Aging Gracefully

Guiding Bodies Into Aging Gracefully

By understanding how “zombie cells” contribute to age-related conditions, Dr. Nathan LeBrasseur hopes to find a healthy, robust aging process.

By Dan Samorodnitsky, Ph.D. Photography by Matthew C. Meyer

Nathan LeBrasseur, Ph.D., M.S., is, in his own words, a nontraditional clinician-scientist.

“As a young man, I didn’t know what I wanted to do,” he says with a laugh. “I started in physical therapy.”

Growing up in a paper mill town in northern Minnesota, he was the first in his family to pursue higher education. As a physical therapist, he worked in a sports medicine clinic, helping people to jump higher, throw farther, run faster. But eventually he realized he wanted to do more. Physical therapy was rewarding, but he was pushing people who were already at 90% up to 100%. And not all patients were like that.

“I realized that hospitalized older patients were often just trying to get out of bed or rise from a chair. That realization made me redefine my understanding of ‘human performance’ — as a physical therapist I was focused on optimizing human performance, and that experience changed what I thought of as ‘optimizing.’”

A New Path

To find a way to boost that performance, Dr. LeBrasseur went back to school for a Ph.D. Now, as director of the Mayo Clinic Robert and Arlene Kogod Center on Aging and the Noaber Foundation Professor of Aging Research at Mayo Clinic, he’s occupied with a new question, or rather, several questions: “What is aging, in a biological sense? What is this thing that creates so many vulnerabilities? What are the effects of the wear and tear of life on our bodies?”

The big, overarching idea that guides Dr. LeBrasseur and his colleagues at the Kogod Center on Aging is that if doctors can better understand the aging process, that process can be delayed, managed or softened, instead of “playing a game of whack-a-mole,” as Dr. LeBrasseur puts it, with common diseases of aging like Alzheimer’s, Parkinson’s and cancer.

An Inevitable Fate

Aging is really because of the laws of physics. Due to the effects of entropy, things — including our bodies — tend to break down and become more disordered over time. The Kogod Center on Aging is measuring damage to the human body, to its cells and tissues. They are delving into the “hallmarks” of aging — damage to DNA, mitochondrial dysfunction, how often the proteins in our body are replaced as they wear out, and top of mind for Dr. LeBrasseur, something called senescent cells.

These are cells that are worn out, used up and damaged. Like an old car, perhaps they can be repaired, or maybe they need to be broken down, their parts recycled and retired. These are the two main fates for old cells: death, by a self-destruct mechanism (called apoptosis), or repaired to carry on.

Senescence isn’t just a part of getting older. In biology, it also plays a role in development. For example, how does an organ know how big to get? That’s senescence. When the cells of a particular organ stop growing and dividing, it’s a signal to the rest of the body that the organ has reached its adult state.

You, me, your dog, your coffee machine — aging happens to everything and everyone.
— Nathan LeBrasseur, Ph.D., M.S.

However, as we age, senescent cells take on a more dangerous role. These are known as zombie cells — damaged cells that, by chance or by mutation, evade both the body's repair mechanisms and apoptosis pathways. These zombie cells simply carry on in their damaged state. They continue to perform their cellular duties, to the best of their abilities, but can cause more problems than they would if they just self-destructed.

When senescent cells linger, that’s bad. They secrete a lot of toxic molecules into the body that hinder normal processes. This manifests in all kinds of ways, and as a body ages, its ability to heal slows, thanks to damaged cells.

“Not only is the ‘seed’ damaged,” says Dr. LeBrasseur, pointing to damaged cells, “but the ‘soil’ is now toxic. Even if there are other healthy cells around, the toxic secretions of damaged zombie cells compromise those healthy cells and their healing process.”

Where to go from here? Dr. LeBrasseur says they don’t have to reinvent the wheel. According to him, the big breakthrough was in 2011, when zombie cells were one of the scientific breakthroughs of the year, as ranked by Science.

Understanding the Aging Process

A group of researchers at Mayo Clinic, including Dr. LeBrasseur, removed zombie cells in a mouse model and saw that doing so delayed a litany of age-related disorders. By injecting mice with a drug that made senescent cells self-destruct, they delayed the onset of cataracts and muscle weakness. Mice without senescent cells could run and scurry longer than control mice, while maintaining their weight as they aged, something that becomes a struggle for aging humans. The mice didn’t live longer, but they lived healthier, happier lives.

While these sorts of approaches are theoretically possible, more work needs to be done to develop safe and effective senescent cell-targeting drugs for humans. Already, they point to opportunities to potentially manage and ease the process of aging.

“The foundational things for healthy aging are the things that you already know about — exercise, eating well, socializing and so on,” says Dr. LeBrasseur. “These activities are critical for aging well, and I don’t know how much we can change that with just drugs. And you have control. It doesn’t cost money to do those things, but it does take personal effort. Some people are disappointed with those kinds of answers.”

Dr. LeBrasseur says to think of aging with a holistic perspective — choices made all through life have an effect. It’s not the individual meals you eat but the lifetime of food choices, not the one walk but a lifetime of walking every day. In essence, humans prepare their whole lives to become old. Everyone will eventually develop some health condition, and they start to pile up.

But Dr. LeBrasseur wonders: “Can we boost the resilience of older adults before they even get sick and have to undergo harsh treatments like surgeries and chemotherapy?”

In addition to encouraging patients to engage in healthy lifestyle activities, the team at the Kogod Center on Aging is continuing to explore the effects of zombie cells, with the goal of eventually finding ways to prevent their negative impacts on our health. In the future, Dr. LeBrasseur hopes that for older adults, those twilight years can be a whole lot smoother.