Tufts researchers explore the science of aging

Anti-wrinkle creams, superfoods that keep you young, dietary supplements that promise improved memory, "immortal" cells that can renew themselves forever-;in our stores and media, claims about aging abound.

But do you actually understand how your body and mind change as you age? How much of aging is particular to you, and how much can you control? Do you know how you want to age, or what aging well means? Do you know what aging is?

The bottom line is, for a phenomenon that's happening to all of us at this very moment, aging remains remarkably mysterious.

Experts across Tufts University are working to change that. At the School of Medicine, they are studying cardiac health in postmenopausal women; at the School of Dental Medicine, they are putting students in special suits to simulate aging; and at the Friedman School of Nutrition Science and Policy, they are teaching future dietitians, scientists, and policymakers about the nutritional needs of older adults.

And the hub of it all is one of the largest research centers in the world that focuses on healthy aging and its relationship to nutrition and physical activity: the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts.

"To me, aging is the most compelling issue in modern biology. It's surprisingly complex," said Christopher Wiley, a scientist on the Basic Biology of Aging Team who studies the role of nutrition and metabolism in aging at a cellular level. "There are so many ways of getting at the same problem. There's always going to be something new to figure out and something new to study."

It's an exciting moment in the science of aging-;and an important one, said Sarah Booth, director of the HNRCA and senior scientist and leader of the center's Vitamin K Team. Within 10 years, people aged 65 and older will outnumber those 18 and younger, according to the U.S. Census Bureau's 2017 National Population Projections. This will significantly affect public health and the health of our economy.

According to the Administration on Aging, part of the U.S. Department of Health and Human Services, consumers aged 65 and older spent an average of $6,668 on out-of-pocket health care costs in 2020, up 38 percent since 2010. In 2017-2018, 40.4 million people provided unpaid care to a family or non-family member aged 65 and older.

Booth also pointed out that one in five people aged 65 or older remain in the workforce, which raises questions about how to accommodate different generations with different skills, experiences, work philosophies, and physical needs in the workplace. "Aging is the new reality," Booth said. "And most people aren't even thinking about the implications for society."

To adjust to this new normal, we must understand what aging really is. And from Tufts' converging studies, an answer is emerging-;a deeper, more nuanced one that challenges and often contradicts the popular understanding, that could transform how each of us lives, as well as our whole society.

We know about aging now what we knew about cancer in the 1980s. We're just at the tip of the iceberg here. But we're already at a point where we are testing interventions for human aging, which is absolutely fascinating, and really exciting."

Christopher Wiley, Scientist

How to talk about aging

Why do we still know so little about aging? Humans have always gotten older-;yet the term "geroscience," the study of the mechanisms of aging, didn't even exist until a decade ago.

Aging research is new, because aging as we know it-;large numbers of people spending long periods of time in older age-;is new. Life expectancy in the U.S. was only about 62 for men and 64 for women 100 years ago, in 1943. In 2020, persons reaching age 65 had an average life expectancy of an additional 18.5 years (19.8 years for women and 17.0 years for men).

So what is aging, anyway?

Here's what it isn't, according to Wiley: conditions such as arthritis, cataracts, heart disease, Alzheimer's, Parkinson's.

"We associate these chronic degenerative diseases with aging, because their incidence rates increase exponentially among older people," Wiley said. "The basic processes that underlie aging can drive chronic degenerative conditions. But chronic degenerative conditions are not aging, per se."

Another thing that aging is not, at least for the purposes of most research: what happens when we're younger. We're technically getting older from the moment we're born, but that doesn't become relevant at the HNRCA until we reach a certain age. "We're really talking about the processes that occur either positively or negatively at a specific segment of the lifecycle at the opposite end from infants: older adults," Booth said.

"Older adults" is the proper term, Booth emphasized-;not "elder," "elderly," or "old," which are vague, negative, and no longer used in the scientific literature.

How old is an older adult? It depends who you ask. A number of federal agencies set it at 65, but that number may date back to the average lifespan of American men in the 1930s, when social security was established in the United States, Booth said. Other federal agencies focus on adults 60 and older, while the American Association of Retired Persons works with those 50 and older.

Sixty-five is also a common cutoff in research on older adults, Booth said-;although studies of older women often use menopause, because it's a distinct, measurable event that changes aging. Studies of sarcopenia, or muscle wasting, often focus on adults in their 80s and 90s, which is the period when that disease tends to develop. "It really depends on the scientific question," Booth said.

Sensitivity and attention to nuance are needed not only to research aging, but also to talk and think about it-;and the HNRCA is up to that challenge. "It's really exciting that we have a lot of people who understand the importance of looking at healthy aging from a multidimensional perspective, and an institution that not only understands the science, but respects the process of aging," Booth said.

What is aging?

So what is the process of aging, biologically?

Wiley defines it simply: It's a loss of function over time.

It happens to everything. Metal rusts and loses strength. Springs get less springy. The wind-up toy stops working.

More complex objects have more parts to wear down, more functions to be lost, and a much wider range of possible failures. "You could have two cars, same makes, same model, driven by the same person, and two different things will fail on the car," Wiley said.

The same thing happens to the human body. "There's damage to your cells happening all the time," Wiley said. Except the body, with its many interlinked processed, systems, and levels of organization, is much more complex than a car-;and therefore has many more points of potential failure.

When you think about just how intricate and finely tuned the human body is, Wiley suggested, the real mystery isn't why it fails-;it's why it survives. "The fact that life works is amazing," Wiley said.

The body does have one advantage: it's self-repairing. "The body tries to maintain itself and restore homeostasis even in the face of all this stress and all this damage. We have these really sophisticated programs for dealing with these points of failure," Wiley said.

But as we get older, Wiley said, cells are unable to keep up with the repairs. Small failures accumulate.

"It can start with something as simple as a broken molecule, one little thing that goes wrong in one cell, and then it's like the butterfly effect," Wiley said. "The tissue starts struggling, and then the organ, and then your entire body."

Different types of cells express damage in different ways. The lenses of our eyes stiffen and cloud. The cartilage in our joints thins and our ligaments shorten, losing flexibility. Blood vessels harden, bones become fragile, and muscle and brain mass decline.

We can replace things-;hips, livers, even hearts-;but not forever. We're too complex, and the damage too steady.

"There's definitely a misconception out there that we're trying to make people immortal. But there is never going to be an immortality vaccine," Wiley said. "There's never going to be one thing that defeats all of aging. There's always going to be another point of failure."

The goal of health aging

If we can't defeat aging, what can we do?

Figure out how to live longer, is most people's first thought. "There's a lot of discussion and interest in the space of how to extend our lifespans, and more and more private philanthropy looking for magic bullets," Booth said.

But there's a fundamental limitation to studying how to make human lives longer. "We don't get grants for a hundred years," Wiley said. "And who's going to do it?"

Also, living longer doesn't address the real problem-;and could actually make it worse. "The challenge is that more and more people are living disabled for longer periods of time before life ends, which has huge consequences for society in terms of health care, culture, and ethics," Booth said.

That's why more and more research and federal funding focuses not on extending chronological age (the number of years an organism has been alive) but on slowing down biological aging, or how "old" our cells and tissues actually are and how well they function. Lengthening the time in which we can continue to move around, care for ourselves, and participate in social life and activities, is a worthier goal than extending years of suffering, Booth argued. "We're really talking about helping people live as long as they can in a healthy way, free of disability caused by chronic disease," Booth said.

People tend to use the word "longevity" to refer to both longer life and better health as we age, which is why Booth prefers "lifespan" for chronological age and "healthy aging" for improving biological age. "We've got a very confusing national debate right now because people are conflating a lot of different concepts," Booth said. "We need to be more thoughtful on how we define terms, or they could actually be detrimental to the concept of healthy aging."

"Healthspan" has promise as a term for our years free of disability, Booth noted-;but it doesn't cover the increasing numbers of older adults who are losing their health but retaining their abilities through the new field of gerotechnology, which spans smartphone features, ambient systems, robotics, artificial intelligence, and more. "We are continuously moving that threshold of that ability to live independently," Booth said. "It's a really exciting time."

The many drivers of aging

How do we lengthen people's healthy years?

First, according to Booth and Wiley, we must solve a mystery central to aging: why no two individuals age alike.

"There's really not much difference between babies, but you see much greater variation in biological aging in older people," Booth said. "The big challenge is, why do some people have these aging processes that don't result in chronic disease-related disability, and others do?"

Many drivers of aging are mechanisms that we have in common. We all have telomeres-;the protective caps of our chromosomes, often compared to shoelace tips-;that wear down over time, leading to errors in DNA copying and an end to cell replication (called cellular senescence).

But mice have telomeres much longer than those in humans, and they live just three or four years, Wiley pointed out. Plus, humans vary in both telomere length, and how quickly they wear down. "There's this belief out there that if you were just able to lengthen telomeres, you wouldn't get old," Wiley said. "But all our evidence says it's a combination of things."

One of these things is diet, which the HNRCA is now studying in greater depth than ever before. One of six institutes nationwide to receive a grant from the National Institutes of Health-;in the amount of $8.5 million-;for the cutting-edge field of precision nutrition, the HNRCA is embarking on a major study of how and why certain diets have different effects on individuals' aging and other biological processes.

Other factors that influence aging are genetics, exercise, environment, stress levels, and even socioeconomic class, to name just a few. But we don't know how much each contributes-;it's hard to isolate one factor, or even to look at all of them. "We are an accumulation of everything since we were conceived-;and even before that, because now there's even evidence that prior generations influence who we are," Booth said. "You're looking at a lot of factors, and you're looking across an entire lifetime. That's a lot of data points."

Different disciplines, same problem

So how do we look at everything that ever happens to us across our lifetime, and use it to understand aging?

We do it together, according to Booth. The HNRCA brings together more than 40 scientists working across a wide range of fields to study how exercise and nutrition accelerate or slow down the common biological processes of natural aging. It has research teams focusing on the brain, the heart, the eyes, and bones, along with cancer, obesity, and more.

"We're bringing the broader sociological demographics to our research to understand why some groups in the population have accelerated aging compared to others," Booth said. "We're bringing in engineers, mathematicians, artificial intelligence, and machine learning to look for patterns and predictive algorithms in the data from all these different disciplines."

The HNRCA also partners with dozens of departments across the university, whether examining fruit flies with the Department of Biology in the School of Arts and Sciences or comparing human and canine muscle wasting with the help of the Cummings School of Veterinary Medicine.

"We're looking at the same question through different lenses with different tools, technologies, and perspectives," Booth said. "Progress in aging research is only going to be achieved by bringing together different disciplines addressing the same problem."

And slowly but surely, that progress is happening, says Wiley. Researchers are making headway in the question of why two worms with the same genetics have different lifespans, zeroing in on small fluctuations early in life that become large differences later.

"The biggest change I've seen in the past ten years is that we really are finding new, different ways of actually intervening somewhere that could potentially extend the healthy years of life, and prevent people from getting age-related diseases," Wiley said.

Public perception has yet to catch up with the new ways scientists are thinking about and researching aging, Wiley said, but there's one thing he hopes people understand.

"What aging research is really trying to do is compress the morbidity and make it as small as possible-;to alleviate suffering," Wiley said. "I think that's a much more humanitarian goal, and I think we're having a lot of success with those efforts."