Imagine a day in the not-too-distant future. You’re in your late 40s, and it’s time for a special doctor’s visit. The physician reviews your lifestyle, sleep habits and health history and orders some blood work to compare certain biomarkers with baseline measures taken when you were in your 20s. Then she gives you a personalized prescription for change that includes a diet that mimics the effects of fasting and a drug that helps your cells clear out malfunctioning proteins. The goal? To make you age more slowly and lengthen your “healthspan.”
If it sounds like science fiction, you’re right – for now. But researchers in the field of geroscience, which explores the relationship between aging and diseases like cancer, heart disease and Alzheimer’s, see that day coming. They are marshalling evidence that the same cellular processes that drive aging also result in those diseases, and that it’s possible to slow the damage down. “The idea is that if you can treat the underlying causes of aging, you can delay all of these things as a group,” says Dr. Steven Austad, scientific director of the American Federation for Aging Research and a professor at the University of Alabama–Birmingham. “That’s a whole different way of thinking about medicine.”
The goal is not to extend lifespan, though that may indeed happen. Instead it’s to extend the length of time you’re healthy and active. “We want people to be in their 80s and feel like they’re in their 50s and 60s,” says Brian Kennedy, president and CEO at the Buck Institute for Research on Aging in Novato, California. That’s not far-fetched, according to The New England Centenarian Study at Boston Medical Center, whose current subjects range in age from 100 to 115 and have been followed in some cases for 10 years to get a sense of what underlies the longest lives and healthy aging. People who make it to 109 and beyond have generally been independent and quite healthy well into their 90s and even past 100, says Dr. Thomas Perls, founder of the study and professor of medicine. One 106-year-old participant maintains her own garden and does her own canning; a 110-year-old still plays the piano.
Evelyn Folstrom, 109, uses a walker to get around and lives with her daughter and son-in-law in Northfield, Minnesota, but she can still read her daily devotionals and Bible (with her glasses), write letters to her 13 great-grandchildren and occasionally get to church. She says she hasn’t had any major health issues, other than two bouts of colon cancer in 1986 and 2003 that were “taken care of promptly.”
That kind of “compression of morbidity” would be good not only for individuals (who wouldn’t like more time to volunteer or play with grandchildren?) but also for society, says Kennedy. A projected one-fifth of Americans will be 65 or older by 2030, and their health care costs will be overwhelming if they have multiple chronic diseases and cope with disability.
Working with a range of organisms from yeast to worms to rodents, scientists have homed in on several interrelated processes they suspect drive aging. These probably differ in their effect between people, says Felipe Sierra, director of the division of aging biology at the National Institute on Aging. (Thus that personalized aging strategy at your future physical.)
Proteostasis, for one, is a fancy name for the quality-control system at work in your cells. Like a factory, a cell has ways to ensure the proteins it makes are up to snuff, says Dr. Ana Maria Cuervo, co-director of the Institute for Aging Research at Albert Einstein College of Medicine in New York. If they’re not, the malfunctioning proteins are supposed to be broken down and used to build new proteins or as energy. Cuervo’s lab specializes in autophagy, one part of that system that works less well with age and is linked to Alzheimer’s and Parkinson’s disease. Her lab is looking for interventions, whether lifestyle or drugs, that might repair this age-related quality-control decline.
Another area of exploration is inflammation. Low-grade, chronic systemic inflammation in the absence of an infection is a factor in most age-related diseases; it’s even known as “inflammaging.” The sources of it aren’t well known, but scientists are investigating possible contributors, including a state called cellular senescence. When cells undergo mutations or other damaging disruptions, normally the defect is fixed or the cell dies. But sometimes it slips into a kind of twilight zone, no longer dividing but not dying, either. Senescent cells can sometimes produce pro-inflammatory proteins that can damage other cells, says Dr. James Kirkland, a professor of aging research and director of the Kogod Center on Aging at the Mayo Clinic in Minnesota. And they’re strongly associated with diseases of aging like cancer, atherosclerosis, diabetes and dementia.
Kirkland and his colleagues wondered what would happen if senescent cells were removed. In mice, they’ve shown that certain drugs called senolytics can do just that – and slow the progression of age-related changes and even partially reverse them. In a study published last year, the researchers found that a commercially available cancer drug and the supplement quercetin, an antioxidant, improved cardiovascular function, exercise endurance and osteoporosis, plus increased healthspan when used together.
Kirkland cautions that it’s not yet clear whether the benefits will carry over into humans. The abandoned medicine cabinet of history is full of drugs that cured diseases in rodents but didn’t pan out in human beings. But often those diseases – take Alzheimer’s, for example – must be engineered into the lab animals since they don’t occur naturally. Since aging is a process that seems to happen similarly across species, researchers are cautiously optimistic that the research will translate.
Other drugs, too, are being eyed for their potential. A top contender, which has increased both lifespan and healthspan in mice by targeting a protein that controls key cellular functions, is rapamycin, used in people to prevent rejection of transplanted organs. Matt Kaeberlein, a professor of pathology at the University of Washington Medical Center in Seattle, is now studying whether rapamycin has a similar effect in pet dogs, which he thinks might be great models for aging research because they share an environment with humans and are genetically varied.
Kaeberlein and his team have so far put 25 healthy dogs through a 10-week trial of rapamycin; while he can’t yet talk specifics, changes in cardiac function show a trend similar to the benefits seen in mice. He is planning a larger study that would follow 600 dogs randomized to either the drug or a placebo for at least three years to see whether the drug impacts vulnerability to cancer and cardiovascular disease, immune function, mobility and cognitive function. “We want to really assess whether aging has been delayed,” he says.
One drug study is actually approaching the human stage. Dr. Nir Barzilai, director of the Institute for Aging Research at Einstein, is spearheading an effort to test metformin, a diabetes drug, as a bulwark against a host of common age-related diseases. That’s a very different strategy from the usual one of matching a drug to a single disease. The researchers settled on metformin as the first candidate for this type of study because it has a long track record of safety, and epidemiological evidence in humans suggests it might lower the risk for several different diseases. Now the search is on for necessary funding – some $64 million to track 3,000 people over six years, Barzilai says. The start date of the trial will depend on funding, with a goal of beginning within a year, he says.
What, if anything, can people do now to lengthen their healthspan? Some clues come from studies of members of the Seventh-day Adventist Church, which recommends members exercise regularly, eat a well-balanced vegetarian diet, and avoid tobacco and alcohol. That advice seems to have paid off in Loma Linda, California, which has a significant concentration of Adventists and has been identified as the only U.S. “Blue Zone,” an area recognized by researchers as a place where people tend to “live measurably longer, better.” (The other Blue Zones are Sardinia, Italy; Okinawa, Japan; Costa Rica’s Nicoya Peninsula; and the Greek island of Ikaria.)
Researchers at Loma Linda University have for decades studied the lifestyle habits of church members, with 96,000 people in the U.S. and Canada currently enrolled. A study published in 2001 of more than 34,000 non-Hispanic white Adventists in California found that a 30-year-old female participant could expect to live 7.3 years longer and a male could expect to live 4.4 years longer than other white Californians. Besides exercise and the vegetarian diet, regular consumption of nuts and being careful about body weight were factors making a difference.
Studies like this can’t determine whether lifestyle behaviors actually led to longevity. But the evidence “is about as good as you can get,” says Dr. Gary Fraser, principal investigator of the ongoing Adventist Health Study-2 and a professor of medicine and epidemiology at Loma Linda. The findings suggest that while genetics are likely heavily involved in living past 90, most people are equipped to reach that age if they make the right choices, Perls says.
Some researchers are also focusing on when, as opposed to what, you eat. Intermittent fasting, which involves periods of little or no food, have shown benefits in mice. Valter Longo, director of the University of Southern California Longevity Institute, is studying a diet that mimics fasting, with five consecutive days of a low-protein and low-sugar diet amounting to 800 to 1,100 calories per day. For most healthy people, that could be done once every three to six months, he says. Animal studies suggest that starting to eat normally again after a period of food scarcity can regenerate organs by turning on stem cells. And a small pilot study found that a similar diet in humans improved such markers for age-related diseases as trunk fat, glucose and C-reactive protein, a measure of inflammation. A larger trial of 100 people is finished but the results haven’t yet been published, says Longo.
Importantly, the diet is safer than outright fasting, says Longo, who, along with his lab members and family members, follows the regimen. But he warns that people who want to try it should speak with their physicians, and that it isn’t appropriate for diabetics taking medications. Nor are the long-term effects known (though data from clinics that supervise fasting for 10 to 21 days indicate periodic fasting is safe). Other researchers are looking at variations on this theme, such as restricting food consumption to an eight-hour window in the day.
Research also suggests that stress management plays a role. Prolonged psychological stress seems to promote many hallmarks of aging, including inflammation and the shortening of the protective caps on the end of chromosomes known as telomeres, according to Elissa Epel, a professor of psychiatry at the University of California–San Francisco. Short telomeres are associated with the early onset of disease, though it’s not known whether they actually cause aging. But she and her colleagues, led by Eli Puterman at UCSF, have found that a diet of healthful foods like fruits, vegetables and nuts and fewer unhealthful ones like fried foods and soda, along with regular exercise and quality sleep, can counteract those effects. Separately, she also recommends fostering social connections and relationships, and purpose in life.
Folstrom, who will become a “supercentenarian” when she turns 110 this year, would seem to be evidence supporting much of this advice. She’s had a “normal, happy life,” growing up on a farm and living mostly in her beloved Minnesota with her husband, a pastor, until he died in 1999. Along the way she worked in various jobs, including as a country schoolteacher and a switchboard operator. She never drank or smoked. “We have to take care of our bodies,” she says. She’s always been religious and credits God’s plan for her longevity.
Will geroscience help more people follow in her footsteps? The research is very exciting, says the NIA’s Sierra, though “we are really in the infancy of this.” So stay tuned.