The puzzle of aging: UW experts are piecing together new ways to live longer and better

When it comes to aging well, heredity is only half of it: Everything from mitochondria to marital status can factor in.

“When I started working as a nurse in 1968, aging was something people suspected happened much earlier: You get old, you get sick, and you die,” says Nancy Fugate Woods, dean emerita of the UW School of Nursing. “Retirement was seen as a quick prelude to the end of your life.”

But today, thanks to improved hygiene, the development of medications, and clean water, Americans don’t face the level of infectious disease they did at the start of the 20th century. In fact, we’re living 30 years longer than our ancestors just a few generations ago. So now it’s not just a question of how long we live, but how well, says Woods.

“My generation is not satisfied with ‘you get old, you get sick, you die,” says Woods, a baby-boomer. “We have a tradition of changing almost every life experience we go through. Now we’re thinking about what we can do that makes this part of the lifespan worth living.”

As humans live longer, they’re more and more grappling with age-related illnesses like heart disease, diabetes and dementia. Over the last decade, thanks in part to medical advances and in part to our changing culture, the visions and views of aging have changed significantly. Sixty is no longer the end of life, but the start of the next chapter.

Woods, ’69, turned 71 in August and retired from the UW after nearly 40 years in academia. Nonetheless, she keeps a lively schedule, understanding that the rigor that comes with collaborating with colleagues, mentoring students and continuing her research will keep her intellect engaged. “Sometimes there is a perception that once we reach a certain age, we need to slow down or not do an activity,” she says. And that is a dangerous way of thinking. Studies show that increased activity, even at nursing homes with residents in wheelchairs, improves both physical and mental well-being.

Recently, Woods and her colleagues have been exploring what it means to “age well,” and how race, economics, sexual orientation and other factors affect our later years. They are studying the notion of “optimal aging,” which allows for disability and disease but emphasizes individuals having the capacity to adapt to the changes aging brings. The way to thrive is to accept change and adjust our behaviors to still be able to do what we want, says Woods. If stability is an issue, for example, use a cane or enlist the assistance of a caregiver. “There is a wide range of possibility beyond just not going out,” she says. “You can still experience high life satisfaction and still experience personal growth, even if you encounter physical and cognitive changes along the way.”

Though she recently retired, Nancy Fugate Woods, dean emerita of the School of Nursing, has simply moved her work to her dining room table. She continues to collaborate on studies on women’s health and positive aging.

Social engagement is also important. Woods devotes energy for her grandchildren and for nurturing relationships with friends. “I believe I am growing in my understanding as a human being because of that,” she says. She readily admits, even after a career that included studying midlife and older women’s health, she doesn’t have it all figured out. “I am grappling with what my next chapter should be,” she says. “I’m trying to fill it with discernment, with activities that have meaning, where I make contributions.”

Perhaps the most important lesson we have today, she says, is no matter how old you are, it’s never too early to start thinking about how you will age, and almost never too late to make changes.

Aging on the mind

When K. Warner Schaie enrolled at the UW for graduate school in 1952, few on the faculty were studying aging, let alone the psychology of it. But Schaie had already undertaken his first exploration of intellectual ability and cognitive decline in older adults.

Schaie, as an undergraduate at UC Berkeley, had administered to retirees a mental ability test designed for children. At the time, few people were studying cognitive change in adults, particularly seniors. Sitting in his living room on Queen Anne Hill, with a view of Lake Union in front of him and fresh stack of library books beside him, Schaie, now nearly 90, reaches into his memory for the details.

“I was intrigued. Someone said there’s a senior center out at the marina in San Francisco,” he says. Testing older people there and people of different ages at another facility, he found that adults and those in middle age performed better on the mental skills test than high school students. At a time when the prevailing belief was that people reached their intellectual peak in their 20s—around the time they peaked physically—this was a revelation.

At the UW, Schaie sought to repeat his study. It was his good timing that Group Health Cooperative had just formed and one of his professors was on its advisory board. Schaie added his own questions to a Group Health survey. He measured verbal ability, numerical ability, reasoning, word fluency and spatial orientation and came up with some surprising results.

The findings of that first 1956 study became the basis of his dissertation as well as the foundation of the Seattle Longitudinal Study, a 47-year effort to follow the participants and understand how their abilities changed with age. Returning every seven years to collect data, “it turned out the findings were very interesting. Some people as they got older had gotten worse, but some had gotten better,” says Schaie. Looking at the same people over time, Schaie and his team found that for most people cognitive functioning improves from young adulthood to midlife, declines slightly in the 60s and progresses downward into the 80s.

As agents of our own development, we can make lifestyle decisions that help us keep up our mental abilities.

He was also curious as to how rigid or flexible the participants were in their behaviors. For example, could they easily shift from one task to another? Schaie gives the example of breakfast where those who exhibit rigid behaviors would eat the same food at the same time every day. Schaie’s study found that people who are very rigid don’t do as well in late life. The reason? Old age is a time of rapid change and requires a lot of flexibility, he says.

He also found that factors like having above-average education (today in Seattle that means more than some college), a job that is high in complexity and low in routine, success in life, and marriage helped delay mental decline. Health also plays a major part, particularly if you are free from cardiovascular disease, which Schaie found took a toll on brain function.

After finishing his master’s and Ph.D. in psychology, Schaie rose to national prominence for broadening our understanding of the psychology of aging. His work changed public policy, causing government agencies in the United States and Canada to raise the mandatory retirement ages in a number of fields. While a 55-year-old brain might not be as good as a 30-year-old brain at something like calculus, Schaie says, middle-aged people are better at managing large-scale projects with multiple pieces and numerous people, and are generally better at planning, reasoning and problem-solving.

Throughout his career, Schaie he kept the Seattle Longitudinal Study going and in some cases managed to capture data from multiple generations of the same family. In the 1980s, the study broadened to explore how a person’s intelligence might be preserved or modified. The study already showed that we may start to experience some cognitive decline in our 20s and 30s, particularly with perceptual speed.

Sherry J. Willis, an educational psychologist who collaborates with Schaie on the Seattle study and is also his wife, offered participants over 64 an opportunity to try intensive brain training to restore function. She and Schaie theorized that mental loss might be due to lack of use and could be reversed. Going to participants’ homes for regular sessions, researchers led them in a series of exercises in memory, reasoning and speed of processing. They found that people who had continual training over periods of time maintained or improved their cognitive functioning and were better able to do tasks like manage their own checkbooks and medicines, and live independently longer.

As agents of our own development, we can make lifestyle decisions that help us keep up our mental abilities, says Schaie. In one research paper, he put is this way: We can engage in stimulating activities or be couch potatoes. Furthermore, we should think about being flexible, undertaking activities that stimulate our intellects like reading and traveling, trying new experiences and attending cultural and educational events, he says.

Schaie, who will be 90 in February, and Willis, now in her 70s, find cruising and exploring new parts of the world, attending conferences, and visiting friends in other cities keeps them engaged on many levels. They are also co-editing a book and work out with a physical trainer once a week. “Don’t just live day to day,” says Willis. “You can’t stop learning. And keep in mind flexibility [in your behaviors] is really important.”

Fight the frailty

That sight of a frail older person who moves slowly and gingerly troubles Oleg Zaslavsky, a faculty member in the School of Nursing who studies lifespan health and innovative interventions. Frailty is a medical syndrome characterized by weight loss, muscle loss, fatigue and limited physical activity. Not a lot is known about the biological mechanisms that cause frailty in older adults. But we do now know that frail people have an increased risk of falls, fractures, disability and mortality, says the assistant professor. They need more health care and need it sooner than their robust counterparts.

Frailty is also a serious concern for medical providers. It affects recovery from all kinds of surgery including out-patient procedures—leading to postoperative complications and longer recovery times. Frail people are more likely to end up in nursing homes and may never regain their level of function after their surgeries, says Zaslavsky. Now he and his colleagues are studying how and why certain people become frail and what can be done about it.

The research shows that people who engage in physical activity are not only healthier but happier, and they stay independent longer. They also spend less on medical costs (nearly $1,000 a year).

Evidence is showing that exercise and nutrition can help. Also, working on getting stronger even if it is just a few weeks prior to surgery improves a patient’s ability to bounce back. As a member of the UW’s De Tornyay Center for Healthy Aging, Zaslavsky works with agencies and facilities that serve older adults, helping them develop physical wellness programs.

In the 1990s, the UW’s Health Promotion Research Center helped develop EnhanceFitness, a research- and evidence-based exercise program for older adults. Today, it is a national model offered through Sound Generations and the YMCA, which provide classes with strength training, balance, stretching and cardio. Participants exercise in groups with certified instructors who can tailor the program to each person’s abilities and needs.

The research shows that people who engage in physical activity are not only healthier but happier, and they stay independent longer. They also spend less on medical costs (nearly $1,000 a year). Understanding this, faculty like Zaslavsky and sociology professor Jerald Herting have looked into why some older adults join and stick with group exercise programs and why some drop out. A recent pilot study, which Herting co-authored, found that those who dropped out of EnhanceFitness either said the class was too hard, that it was too easy, or that they didn’t like to exercise. The first two concerns can be remedied by working with the instructors, but the latter is a broader concern, notes Herting. The study also found that white people were more likely to drop out than those of other ethnicities. Now the challenge, notes the report, is engaging older people who are less inclined to be active.

Perhaps medical referrals and better outreach explaining the benefits of exercise will help. In 2014, the Centers for Disease Control funded a $3.75 million grant to the School of Public Health to conduct additional research into healthy aging. Efforts include finding ways to get physical therapists and primary care providers to recommend senior exercise programs not only to fight frailty and save medical costs, but because regular exercise is linked to reduced risk of dementia and Alzheimer’s disease.

Aging and disease

While much of the nursing and sociology research at the UW focuses activity and behavior, there’s still a lot to learn about what age does to us on a cellular level. That was the start of UW pathologist Matt Kaeberlein’s hunt for ways to slow aging.

As an undergraduate at Western Washington University, he heard  a talk by MIT biologist Leonard Guarente, one of the country’s leading experts in the biology of aging. “It fascinated me that you could study something as complicated as aging,” says Kaeberlein, now an internationally-recognized expert in his own right. His work has been published in Nature and Science and featured in The New York Times.

In 1997, Kaeberlein went to work in Guarente’s lab, helping zero in on genes that might increase longevity. That led to a postdoctoral position in Stanley Fields’ lab at the UW. Today Kaeberlein is known for his work toward increasing lifespan and delaying the onset of disease. With nine postdocs, five grad students and more than 40 undergraduate researchers, he also has one of the liveliest labs on campus.

Matt Kaeberlein

Leading one of the liveliest labs in the UW Health Sciences complex, biologist
Matt Kaeberlein is on the hunt for compounds that can change the mechanisms of aging.

“While aging is not a disease, it does drive disease,” Kaeberlein says. As you age, he explains, your risk increases of getting certain diseases. What about getting older makes us more likely to develop chronic illness? he asks. Rather than focus on an individual disease, Kaeberlein and his colleagues are targeting aging on a molecular level, seeking interventions that slow aging and stave off chronic disease and disability. He is also among the UW researchers exploring mitochondrial diseases, which affect nerves and muscles. Mitochondria are what generate energy for cells. Now there is evidence that mitochondrial dysfunction has a role in aging and contributes to age-related disorders like Parkinson’s disease, Alzheimer’s disease, diabetes and some cancers.

It’s an exciting time in the field where researchers are starting to develop evidence that specific interventions (like rapamycin, a drug that Kaeberlein has been working with that prolongs the lifespans in yeasts, fruit flies and mammals) do work. “People are starting to think about clinical trials,” he says. “We’re starting to ask how we can take what we’ve learned in the lab out to the real world.”

But when it comes to trying trendy treatments and drugs on ourselves, Kaeberlein urges caution. Fad ideas like calorie restriction or “young blood,” the notion that infusions from a younger person might reverse age-related impairments, have not been rigorously tested and could even do harm, he laments.

For himself, Kaeberlein’s practice is simple. Practical. He tries to eat healthy foods and exercise regularly. “I’ve gotten better on that than I used to be. I also don’t smoke and I try not to drink too much,” he says. “Those are things that we know with some certainty give you the best chance of living a long, healthy life.”

The Golden Years

Straight out of science fiction, a rare compound found on Easter Island and now being used in humans as an immunosuppressant could be an answer to improving our senior years. Today, UW scientists—with the help of a few canine test subjects—are exploring just how it might help us live longer and healthier lives.

“Let me tell you about its cool backstory,” says Matt Kaeberlein, a UW pathologist with an expertise in the biology of aging. As we sit in his office in the Health Sciences complex, he unfolds a tale that starts in 1964. Canadian researchers collecting soil around the monoliths on Rapa Nui, also known as Easter Island, found a bacteria and an intriguing compound the bacteria produced, which they called rapamycin.

Rayna, a senior-aged golden retriever, took part in the UW’s Dog Aging Project testing a new compound for its ability to delay age-related diseases. Her humans, UW alumni Helen Kyte and Tom Clein of Redmond, volunteered her for the trial.

The compound—which appeared to suppress the body’s immune system—sat on a shelf somewhere for a few decades before it got into the mainstream, says Kaeberlein. Then scientists started exploring its uses for cancer treatment. The FDA eventually approved the drug as an immunosuppressant for organ transplants.

Fast forward to 2004, when Kaeberlein was a postdoctoral researcher at the UW collaborating with biochemist Brian Kennedy. They were performing a genome-wide screening for compounds that could increase the lifespan in yeast. Of the hundreds of compounds they tried, rapamycin stood out. “We were pretty excited about it,” says Kaeberlein. So were other scientists in the field, as well as the National Institute on Aging, a division of the National Institutes of Health, which supports some of Kaeberlein’s research. They broadened the testing to include mice, and the results were similarly promising. Mice given rapamycin have been found to live up to 25 percent longer than their counterparts and seem to have better outcomes with age-related diseases like cancer and Alzheimer’s.

“That really starts to make you think the chances are this could work in people,” says Kaeberlein. That first mouse study had another significant benefit. A glitch in the testing program meant that the scientists weren’t able to give rapamycin to the mice until they were 20 months old, which would be the equivalent of a 60-year-old person. Nonetheless, it worked. This showed that even when the test subjects were given the drug late in life, they received significant benefit.

“It was the first time anyone had shown that you can start an intervention in middle age and get increased lifespan in a mammal,” says Kaeberlein. “It certainly changed the way I think about interventions to target aging.”

Originally, the team thought rapamycin would only slow aging, but now it looks like it can also restore lost function in an older animal. “The data so far suggests that as long as you don’t have a disease that’s terminal, if you’re a mouse, it’s not too late to get some benefit—even rejuvenate certain organs and tissues and extend the period of healthy life from the point you’re at,” says Kaeberlein.

The data so far suggests that as long as you don’t have a disease that’s terminal, if you’re a mouse, it’s not too late to get some benefit—even rejuvenate certain organs and tissues and extend the period of healthy life from the point you’re at.

Matt Kaeberlein

But “how do we take what we think we know in the lab and bring it into the real world?” he says. Teaming up with UW biologist Daniel Promislow and Kate Creevy, a veterinarian at Texas A&M, Kaeberlein turned the focus to dogs. “One real advantage is that with dogs we can do in 10 years what it takes 70 years to do in people,” he says.

“I’m a dog person, I’ve had dogs all my life including three right now,” says Kaeberlein. Promislow is a dog person, too. “In conversations with Daniel about the study of aging in dogs, it occurred to me that companion dogs might provide a really fantastic opportunity to look at rapamycin and how it does outside of the laboratory.”

Rayna is a charming senior-aged golden retriever who loves tennis balls, chasing deer and standing on her hind legs to pick pears from the tree in her yard. When her owners, Redmond couple Tom Clein, ’79, ’81, and Helen Kyte, ’79, heard about the UW’s Dog Aging Project two years ago, they decided to sign her up. “We figured if it doesn’t do any harm and it does extend her life, we should try it,” says Clein.

During the 10-week study, Puget Sound-area pet owners gave their dogs three tablets a week. Some dogs received a small dose, some a larger dose and some a placebo. Among the pups who were given the drug, researchers found positive results and no significant side effects.

Two interesting things were reported by those whose dogs were getting the rapamycin: their activity had increased and, what was more interesting, about 30 percent of them said their dogs were more affectionate. “It could reflect changes in cognitive function,” says Kaeberlein.

It turns out that Rayna was in the group that received the high dose of rapamycin. “The only thing we noticed was that she seemed to be drinking more water,” says Clein. “During and after the trial she showed a pretty steady enthusiasm for activity.”

Now the project is moving into its second phase, which will be conducted out of Texas A&M. The yearlong study will focus on the dogs’ cardiac and cognitive functioning as well as activity. The Dog Aging Project’s long-term goal is to obtain funding for a five-year study to really answer the questions: does rapamycin extend or improve lifespan in dogs like it has in mice, and if so, by how much?