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    Can We Grow Older, But Not “Age”?

    CPMC Scientists Study Prevention & Treatment Of Age-Related Illnesses

    People in their senior years often remark how the latter stages of life are anything but golden. That’s because the effects of aging can range from the occasional ache or pain, to frighteningly debilitating physical and mental illnesses that rob the joy from life.

    What if the aging process could be slowed, delayed or treated?

    That’s the focus of scientists at the California Pacific Medical Center Research Institute (CPMCRI), home to some of the largest, richest data sets about aging in the U.S.

    As part of the San Francisco Coordinating Center (SFCC), this group of research professionals is at the forefront of exploring longevity and common illnesses associated with aging. Age-related neurodegenerative illnesses, including Alzheimer’s disease and dementia, and the physical decline associated with osteoporosis and osteoarthritis, are being investigated to uncover new targets for earlier prevention and treatment.

    “Aging ‘normally’ is not necessarily a good thing,” says Steven Cummings, M.D., CPMCRI senior scientist and director of the SFCC. “If we could find a way to slow down the aging process, people would be less likely to contract many diseases that often impact their quality of life.”

    “We’re not in search of preventing diseases that shorten your life,” he clarifies. “We’re in search of things about our biology, cells, muscles and patterns of sleep with respect to aging. These are all features that, if understood, could help us remain active longer doing the things we love to do. So it’s not just the idea of living longer, but living longer in good health. And that seems to be worth trying to figure out.”

    Walking Slowly—a Link to Other Risks

    One area of aging that Dr. Cummings has studied extensively is slow gait or “dismobility.” This is a condition in which a person can walk only at very slow speeds - no more than 10 feet in five seconds.

    Dr. Cummings and two colleagues recently published their findings in the Journal of the American Medical Association (JAMA). Their research revealed that people who have a slow gait are more likely to fall, break a hip and/or experience other serious mobility injuries. They also found that
    these individuals are at increased risk of contracting other illnesses such as chronic obstructive pulmonary disease, diabetes, congestive heart failure and dementia.

    Even though slow gait speed is a strong predictor of future problems and illnesses, doctors rarely test for it, so it’s seldom recorded in the patient’s medical records. “We think it’s important to know who these people are,” says Dr. Cummings.

    If made aware of this problem, he says, clinicians could conduct studies around what kind of testing could pinpoint underlying causes of the dismobility. They could also proactively develop and prescribe exercise or physical therapy that might improve gait speed and help prevent the onset of other potentially serious problems later.

    Dr. Cummings’ research suggests that gait speed—which is highly reproducible and widely used in clinical and epidemiologic research—should be measured annually beginning at age 70 when the prevalence of dismobility substantially rises.

    Dismobility has serious financial implications. By 2040, the United States is expected to have more than 81 million adults age 65 years or older. Approximately 19 percent, or

    15.4 million of these adults, are expected to have impaired mobility (unable to walk more than three blocks), potentially adding an estimated $42 billion to annual health care costs. Diagnosing slow gait is an important first step toward helping to prevent disability and dependence for millions of elderly and chronically ill patients.

    Exploring Loss of Muscle Function

    In a similar vein, research conducted by CPMCRI scientist Peggy Cawthon, Ph.D., M.P.H., is exploring how age-related loss of muscle mass and strength, a condition defined as “sarcopenia,” can impair muscle function, putting people at risk for falling and suffering serious injuries.

    “Sarcopenia is to muscle loss what osteoporosis is to bone loss,” she explains.

    The human body has the most bone and muscle mass around age 30, which slowly diminishes over time. “But while losing bone is a normal part of aging, there is a point at which you have lost enough that it is characterized as osteoporosis,” she says.

    The same idea applies to sarcopenia. “At some point, the amount of muscle that you have and the amount of muscle function that you’ve lost has crossed over from what is considered ‘normal’ to sarcopenia,” she continues. “Part of what we’re working on is defining those parameters.”

    In addition to losing mobility, people who have reduced muscle strength are more likely to fall, a significant cause of severe and disabling injuries, says Dr. Cawthon. This puts them at risk for fractures, bruising, bleeding and head injuries.

    By learning more about sarcopenia and how to diagnose it, researchers hope to one day develop drugs and exercise interventions (similar to treatments for managing osteoporosis) that could help people retain or improve their muscle strength.

    Mining the Human Genome for Clues to Aging

    “Through my research I am discovering the genetic factors involved in the aging process,” says CMPCRI scientist and professor Greg Tranah, Ph.D. “And not just age-related diseases, but also the ways in which we degenerate while we age. We’re trying to identify specific genetic factors that play a role in physical and cognitive degeneration.”

    Working together with Dr. Cummings, Dr. Tranah is attacking this issue from a different angle. Rather than studying people who are sick, his research teams are studying healthy older individuals. “If we can discover how a centenarian has accomplished a healthy life, at least the genetic factors involved, that will give us leverage for finding ways to improve everybody’s health.”

    In these genetic studies, Dr. Tranah’s teams are discovering genes and specific genetic variants in DNA associated with cancer, dementia, longevity, macular degeneration, depression, sleep and circadian rhythms. Much of his work is focused on examining the role of mitochondrial DNA (mtDNA) sequence variation in human aging, including the age-related changes in mtDNA that impact neurodegeneration, disability, vision and hearing.

    “We’re looking for genetic clues that will lead to the development of interventions for preventing or treating diseases and conditions as they develop,” he says.

    “Genetic research may also help us design more personalized, precise treatments or behavioral interventions,” he continues. “Not everyone responds to medicine the same way. But by identifying genetic markers associated with diseases and degeneration, we hope to pinpoint which people will respond to specific treatments.”

    Of the many age-related diseases, Dr. Tranah says the prevalence of Alzheimer’s disease is particularly terrifying. “The number of deaths caused by heart disease and cancer are leveling out or decreasing,” he says. “But Alzheimer’s is going through the roof as America ages. It’s really frightening. So if we can find a way to delay the onset of Alzheimer’s by even five years, we could keep people healthier longer, relieve the burden on millions of families and save billions of health care dollars.”

    Visit cpmcri-currents.org to view aging-related research and news from CPMCRI investigators.

    Tips for Healthy Aging

    • Exercising.
      Research shows that regular physical activity is vital not only for maintaining physical strength, stamina and flexibility, but also for retaining good mental health and cognitive ability.

    • Staying engaged with others.
      Older people often withdraw, shut down and isolate. People who have regular activities that involve interaction with others stay healthier longer.

    • Getting outside.
      Walking around the block, going on trips, being part of the surrounding life space provides physical, visual and mental stimulation that helps people stay alert and connected.

    • Watching your weight.
      Many debilitating diseases such as diabetes, heart disease, hypertension, as well as joint pain, sleep apnea and other chronic conditions are linked to excess weight.