A focus on living better, if not longer, is reshaping geriatric research nationally -- and Minnesota's own Mayo Clinic is leading the way.
Study subject Pamela Rotty, 54, Rochester, ran up a flight of stairs while Margaret Holets, a bone density technician, left, timed her. Rotty ran the steps twice holding nothing, then carried weights for another portion of the timed fitness test.
Do you want to live to 120, only to feel like you're 120?
In the human quest for longevity -- if not immortality -- it's a question that often gets overlooked.
But it's a core issue for a team of scientists at the Mayo Clinic in Rochester, whose work is reshaping the course of geriatric research nationally.
Over the past three years, Mayo has built one of the largest aging centers in the nation. With 48 geriatricians, 10 geriatric psychiatrists and research supported by 90 federal or private foundation grants, the center has been producing more than 100 research papers annually.
Aging is still the enemy, but the Mayo team's goal is to understand how it works and how to get in its way.
"What elderly people don't want to do is live a very long time at all costs, feeling sick," said Dr. James Kirkland of Mayo's Robert and Arlene Kogod Center on Aging. "What people want is to be independent and free of chronic disease and able to do things on their own."
For Kirkland, it's the difference between lifespan and a relatively new term called healthspan, which means the quality of your life in whatever time you have.
The center scored a high-profile success with the discovery that removing certain cells from the body might slow the onset of age-related diseases.
These "senescent'' cells, which are no longer dividing or producing new cells, are normally removed from the body by natural processes, but they build up with age. Kirkland and his colleagues found that by using drugs to clear these cells from genetically modified mice, they could inhibit the aging process -- and in doing so made the mice less prone to such age-related problems as cataracts, inactivity because of muscle loss and wrinkles because of fat-tissue loss.
"Even if the drug was started in old age," Kirkland said, "we delayed subsequent age-related declines."
The study gained global attention when it was published in the journal Nature, but it represents just one among many research targets at the center. One of Kirkland's colleagues, Dr. Johannes Veldhuis, is examining whether a decline in growth hormone is either a cause or an effect of aging, and if drugs targeting the decline could alter the aging process. A team of researchers led by Dr. Andre Terzic is looking at using elderly patients' own stem cells and transplanting them back into tissues in need of repair. Dr. Sundeep Khosla is studying genetic and age-related causes of osteoporosis and complications from the resulting loss of bone density.
Some studies offer smaller goals and immediate payoffs, such as how to improve recovery from chemotherapy for elderly patients.
Others will take years in pursuit of the aging center's ultimate goal -- to uncover the steps in the aging process that lead to such ailments as Alzheimer's disease, cancer, heart attacks, strokes and diabetes.
Kirkland doesn't foresee an old-age drug that could ward off all these diseases. But if his research identifies the aging process that triggers them, it will give doctors a roadmap for how and when to intervene before they become severe.
"Our paper brings it beyond the level of science fiction," he said, "but it starts us on an extremely long path."
Pamela Rotty gladly signed up to be part of this quest. The 54-year-old from Rochester has seen the difference in healthspan in her own family: Her father's poor health left him unable to travel or fulfill all his retirement dreams, while her grandmother farmed and even took a belly-dancing class in her 90s.
"You don't think about it as much in your 30s and 40s," she said. "But now you're just over the hump of 50 and all of a sudden you're looking over the other side and you're a little more focused. You start looking at the longevity of your parent and grandparents."
Rotty was at Mayo last fall, participating in Khosla's latest study of muscle and bone loss in postmenopausal women. Study coordinators had her run up stairs, then do it again carrying 25 pounds of weight, then sit and rise from a chair 10 times quickly. She also received a full-body scan and a CT scan, and was strapped into a chair to measure how much weight she could lift with her knees.
The former aerobics instructor took it all with a grain of competition, and scowled when a test of her knee lift came in at 48 pounds. Fifty sounded nicer to her.
The study seeks to identify when declines in muscle and bone make women more at risk for osteoporosis and its complications. Often, bone and muscle decline are studied separately. But Khosla (the bone guy) and Nathan LeBrasseur (the muscle guy) are examining how they work together.
"If we can identify the women that are most at risk for losing bone and muscle mass, those are the women that are at risk for loss of healthspan," because of falls that cause hip fractures, Khosla said.
Across Mayo's campus, similar experiments are taking place with mice in LeBrasseur's lab. Mice are being modified genetically to see how the inclusion or removal of certain genetic traits or proteins affect aging and bone and muscle strength.
Researchers hold mice near a wire. When the mice claw the wire, it measures their strength by how hard they pull against it. A mouse-size treadmill measures endurance.
Studies have been inconclusive on whether exercise lengthens lifespan. But LeBrasseur said there is evidence that physical activity improves healthspan -- reducing the odds of certain diseases, for example.
Even so, exactly how exercise affects healthspan isn't fully understood. "It's time now to really start digging into the mechanisms of exercise," said LeBrasseur, an associate professor of physical medicine and rehabilitation. "How is exercise really improving your health?"
Research in this area has a tantalizing payoff. Understanding how the body changes in response to exercise could lead to drugs that maximize the body's response to working out, or stimulate the body in ways that mimic exercise.
"I don't believe we'll ever be able to put exercise in a pill," LeBrasseur said, "but if we can replicate some of the effects of exercise in a pharmacological format, that might be very good for individuals" who are too frail to be physically active.
An exercise drug also could be used in "prehabilitation" LeBrasseur said, giving people preparing for an orthopedic procedure or surgery the benefits of exercise to help improve their recoveries.
Proceed with caution
Of course, tinkering with the body to disrupt aging has to be measured against the potential harm. Senescent cells, for example, might have some underlying and misunderstood purpose. Removing them could disrupt that natural process and lead to unexpected cancers or diseases -- more than offsetting the benefit Kirkland found through his research.
His latest study used mice genetically bred to age rapidly (so the research could proceed more quickly). They also contained genes that would prevent them from suffering harm once their senescent cells were removed with drug therapy. Follow-up research is needed, just for starters, in regular mice before doctors could conceive trials in people.
Not all research in the aging center is so theoretical. A clinical trial is underway to determine how exercise and diet improve chemotherapy treatment for elderly patients and reduces side effects. Colleagues at Mayo's Jacksonville, Fla., campus have discovered that exercise increases the size and function of the hippocampus, the region of the brain that regulates memory and is first to decline with the onset of Alzheimer's disease.
Whether any of this will make a difference in Rotty's lifetime is unclear. She'll diligently return to Mayo for the next three years for fitness tests and body scans. She exercises daily, hoping she'll be able to travel with her husband. He talks of touring the United States in a motor home. She dreams of exploring Europe. It'll be a good thing, Rotty figures, if they're healthy enough to resolve that argument one day.
"My mom is 78, and she walks 4 miles every morning and she swims a half an hour every day," she said. "I'm kind of patterning myself after that, hoping that I'll enjoy the excellent health that she's been able to enjoy. If I play my cards right ..."