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Exercise Can Make Cells Healthier, Promoting Longer Life, UVA Finds

Whether it’s running, walking, cycling, swimming or rowing, it’s been well known since ancient times that doing some form of aerobic exercise is essential to good health and well-being. You can lose weight, sleep better, fight stress and high blood pressure, improve your mood, plus strengthen bones and muscles.

“Whether muscle is healthy or not really determines whether the entire body is healthy or not,” said Zhen Yan, PhD, of the University of Virginia School of Medicine. “And exercise capacity, mainly determined by muscle size and function, is the best predictor of mortality in the general population.”

But why? Yan might have some answers. He and colleagues at UVa are peering inside the cell to understand, at a molecular level, why that workout, like it or not, is so vital to the body. They found that one important benefit involves the cellular power plant – the mitochondria – which creates the fuel so the body can function properly.

Exercise Stresses Mitochondria

Yan and colleagues have completed a study in mice that, for the first time, shows that just one bout of moderate to intense exercise acts as a “stress test” on mitochondria in muscles. They discovered that this “stress test” induced by aerobic exercise triggers a process called mitophagy, where the muscle disposes of the damaged or dysfunctional mitochondria, making the muscle healthier. Yan compares exercise-induced mitophagy to a state vehicle inspection that removes damaged cars from the streets.

“Aerobic exercise removes damaged mitochondria in skeletal muscle,” Yan said. “If you do it repeatedly, you keep removing the damaged ones. You have a better muscle with better mitochondrial quality. We clean up the clunkers, now the city, the cell, is full of healthy, functional cars.”

How Exercise Removes Mitochondria ‘Clunkers’

For this study, Yan and colleagues assessed the skeletal muscle of a mouse model where they had added a mitochondrial reporter gene called pMitoTimer. The mitochondria fluoresce green when they are healthy and turn red when damaged and broken down by the cell’s waste disposal system, the lysosomes.

The mice ran on a small treadmill for 90 minutes and Yan’s team observed mitochondrial stress (signs of “state inspection”) and some mitophagy (towing of the clunkers) at six hours after exercise. Yan explained that exercise in these mice also stimulated a kinase called AMPK, which in turn switched on another kinase called Ulk1. These chemical reactions appear to be important in control of the removal of dysfunctional mitochondria.

“When its turned on, Ulk1 activates other components in the cell to execute the removal of dysfunctional mitochondria,” Yan said. “It’s analogous to a 911 call where a tow truck removes the clunkers. However, we still do not know how these activities are coordinated.”

Some Mice Didn’t Benefit From Exercise

Yan’s lab also deleted the Ulk1 gene in mouse skeletal muscle and found that, without the gene, the removal of damaged or dysfunctional mitochondria is dramatically inhibited, suggesting a new role for the Ulk1 gene in exercise and mitophagy.

“Mice that were unable to do mitophagy did not have the benefit of exercise,” explained study co-author Joshua Drake, PhD, a postdoctoral fellow in the Yan lab. “Even though, from an exercise standpoint, they still were able to run just as far as normal mice, they didn’t benefit metabolically with training.”

Drake pointed out that some people with type 2 diabetes don’t respond to exercise, which is a growing clinical problem. He hopes that continued research in the Yan lab will lead to new discoveries to help these non-responders.

Findings Published

The findings have been published online by the scientific journal Nature Communications.

The study is the product of a collaboration among several laboratories at UVA, Brigham and Women’s Hospital and Harvard Medical School in Cambridge, Mass., and St. Jude’s Children’s Research Hospital in Memphis.

The article is the work of Yan, Drake, Rhianna C. Laker, Rebecca J. Wilson, Vitor A. Lira, Bevan M. Lewellen, Karen A. Ryall, Mei Zhang, Jeffrey J. Saucerman, Laurie J. Goodyear and Mondira Kundu. 

The research was made possible by grants from the National Institutes of Health and the National Institute of Musculoskeletal and Skin Diseases (R01-AR050429, ADA 1-16-PDF-030).


UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

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  • Focused Ultrasound Shows Promise to Treat Parkinson’s Disease Tremor

    An initial test to determine if a scalpel-free form of brain surgery can reduce tremor caused by Parkinson’s disease has produced encouraging results. Further research is warranted, the researchers conclude in a paper published today by the scientific journal JAMA Neurology.

    The pilot study was led by Jeff Elias, MD, of the University of Virginia School of Medicine and also was conducted at Swedish Neuroscience Institute in Seattle. Twenty-seven participants with tremor-dominant Parkinson’s disease were enrolled in the study; the research team randomly assigned 20 to be treated with  focused ultrasound waves on their brains, while the seven others received a fake procedure, to account for any potential placebo effect. (They were later offered the opportunity to have the actual procedure). All had tremor that had resisted medical treatment, and all continued taking their existing Parkinson’s medication.

    The trial participants who received the focused ultrasound procedure had a 62 percent median improvement in their hand tremor three months later. Those who underwent a sham procedure also improved to a lesser degree, however, suggesting some placebo effect. Additional testing is needed to better establish the effectiveness of focused ultrasound for Parkinson’s tremor, the researchers concluded.

    The median age of trial participants was 67.8 years, and 26 were male. The most significant side effects reported were mild numbness on one side of the body, which improved, and numbness of the face and finger, which were persistent. Two subjects also experienced partial weakness that recovered or improved during the study. (The procedure has since been modified to mitigate this risk of weakness, the researchers say.)

    About Focused Ultrasound

    Focused ultrasound already has been approved by the U.S. Food and Drug Administration for the treatment of essential tremor, the most common movement disorder. That approval came after Elias and his colleagues at UVA pioneered the approach. Other researchers are also evaluating focused ultrasound’s potential for treating many other conditions, including breast cancer, brain tumors, epilepsy and pain.

    The technology works by focusing sound waves inside the body to generate a tiny hot spot, much like a magnifying glass focuses light. By carefully controlling this process, researchers can interrupt faulty brain circuits or destroy unwanted tissue. Unlike traditional brain surgery, there is no need to drill or cut into the skull. Magnetic resonance imaging lets the researchers monitor the location and intensity of the procedure in real time, an important safety feature when making permanent changes to the brain.

    Next Steps

    The researchers believe that a larger, multicenter study is needed to better define the potential role of focused ultrasound in managing Parkinson’s disease. 

    “Our findings suggest that the patients likely to benefit from this approach are those for whom tremor reduction is enough to improve their quality of life,” said UVA researcher Binit Shah, MD.

    To learn more about focused ultrasound at UVA, visit To keep up with all the latest developments and research breakthroughs from UVA, subscribe to the Making of Medicine blog at

    About the Parkinson’s Research

    The research team consisted of Aaron E. Bond, Shah, Diane S. Huss, Robert F. Dallapiazza, Amy Warren, Madaline B. Harrison, Scott A. Sperling, Xin-Qun Wang, Ryder Gwinn, Jennie Witt, Susie Ro and Elias.

    The research was supported by the Focused Ultrasound Foundation, the Commonwealth of Virginia, Diane and David Heller, Robert and Molly Hardie and the Prince Charitable Trust.


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • Breastfeeding for 2 Months HALVES Risk of SIDS, Study Finds

    Breastfeeding for at least two months cuts a baby’s risk of Sudden Infant Death Syndrome almost in half, a sweeping new international study has found.

    The study determined that mothers do not need to breastfeed exclusively for their baby to get the benefit, potentially good news for moms who can’t or choose not to rely solely on breastfeeding.

    “These results are very powerful! Our study found that babies who are breastfed for at least two months have a significant reduction in their risk of dying from SIDS,” said researcher Kawai Tanabe, MPH, of the University of Virginia School of Medicine. “Breastfeeding is beneficial for so many reasons, and this is really an important one.”

    Preventing SIDS

    Previous studies have suggested that breastfeeding was associated with a decreased risk of SIDS, the leading cause of death of babies between 1 month and one year of age, but this study is the first to determine the duration necessary to provide that protection. The researchers found, after adjusting for variables that could distort their results, that breastfeeding for at least two months was associated with a significant decreased risk. Breastfeeding for less than two months did not offer such a benefit.

    “Breastfeeding for just two months reduces the risk of SIDS by almost half, and the longer babies are breastfed, the greater the protection,” said UVA researcher Fern Hauck, MD, of the UVA School of Medicine and the UVA Children's Hospital. “The other important finding from our study is that any amount of breastfeeding reduces the risk of SIDS — in other words, both partial and exclusive breastfeeding appear to provide the same benefit.”

    To determine the effects of breastfeeding on SIDS risk, the researchers analyzed eight major international studies that examined 2,259 cases of SIDS and 6,894 control infants where death did not occur. This large collective sample demonstrated the consistency of findings despite differing cultural behaviors across countries, and it provides convincing evidence of the reliability of the findings.

    Based on their results, the researchers are calling for “ongoing concerted efforts” to increase rates of breastfeeding around the world. Data from 2007 showed that a quarter of U.S. babies had never been breastfed, the researchers report. (The World Health Organization has established a goal of having more than half of infants worldwide being breastfed exclusively for at least six months by 2025.)

    “It’s great for mothers to know that breastfeeding for at least two months provides such a strong protective effect against SIDS,” said researcher Rachel Moon, MD, of the UVA School of Medicine and the UVA Children's Hospital. “We strongly support international and national efforts to promote breastfeeding.”

    It remains unclear why breastfeeding protects against SIDS, though the researchers cite factors such immune benefits and effects on infant sleeping patterns as possible mechanisms.

    Findings Published

    The researchers have published their findings in the scientific journal Pediatrics. The research team consisted of John M.D. Thompson, of New Zealand’s University of Auckland; Kawai Tanabe of the UVA School of Medicine; Rachel Y. Moon, of the UVA School of Medicine; Edwin A. Mitchell, of the University of Auckland; Cliona McGarvey, of Temple Street Children’s University Hospital in Dublin, Ireland; David Tappin, of the University of Glasgow’s School of Medicine in Scotland; Peter S. Blair, of the School of Social and Community Medicine at the University of Bristol in England; and Fern R. Hauck, of the UVA School of Medicine.

    To keep up with the latest medical research news from UVA, subscribe to the  blog at


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • Aetna introduces new Medicare Advantage plan with UVA Health System

    Aetna (NYSE: AET) today announced a new Aetna Medicare Advantage plan with a $29 monthly plan premium. This plan is available for Medicare beneficiaries in Charlottesville as well as Albemarle, Fluvanna, Greene, Louisa, Madison and Nelson counties. The Aetna Medicare UVA Health System Prime Plan provides access to University of Virginia Health System’s network, physicians and other health care providers at in-network rates.

    Enrolled Medicare Advantage patients will experience more coordinated care. They’ll benefit from improved information flow to the UVA physicians providing care. This is particularly helpful for patients with chronic or complex health needs. Aetna nurse case managers will assist UVA care providers with care coordination, outreach and follow-up services.

    Plan highlights include a $0 copay for primary care physician office visits, lab services and routine vision and eye exams, along with $0 medical and pharmacy annual deductibles.

    “Aetna is pleased to offer Medicare beneficiaries a new low-premium plan that focuses on collaboration and quality of care,” said Mike Bucci, president of Aetna’s operations in Virginia. “We will work closely with the doctors and health care professionals at UVA Health System to provide each member with a personalized and coordinated health care experience.”

    “This relationship will help us better provide patient-centered care that is focused on health and wellness to Medicare beneficiaries throughout the Charlottesville region by helping us enhance care coordination,” said Pamela M. Sutton-Wallace, chief executive officer of UVA Medical Center.

    This plan will be available in Charlottesville as well as Albemarle, Fluvanna, Greene, Louisa, Madison and Nelson counties during the Medicare Annual Enrollment Period this fall with an effective date of January 1, 2018.

    For more information about the plan, please visit


    About Aetna

    Aetna is one of the nation’s leading diversified health care benefits companies, serving an estimated 44.7 million people with information and resources to help them make better informed decisions about their health care. Aetna offers a broad range of traditional, voluntary and consumer-directed health insurance products and related services, including medical, pharmacy, dental, behavioral health, group life and disability plans, and medical management capabilities, Medicaid health care management services, workers’ compensation administrative services and health information technology products and services. Aetna’s customers include employer groups, individuals, college students, part-time and hourly workers, health plans, health care providers, governmental units, government-sponsored plans, labor groups and expatriates. For more information, see and learn about how Aetna is helping to build a healthier world@AetnaNews

    Aetna Medicare is a PDP, HMO, PPO plan with a Medicare contract. Our SNPs also have contracts with State Medicaid programs. Enrollment in our plans depends on contract renewal. This information is not a complete description of benefits. Contact the plan for more information. Limitations, copayments, and restrictions may apply. Benefits and/or co-payments/co-insurance may change on January 1 of each year. Other providers are available in our network. You must continue to pay your Medicare Part B premium. See Evidence of Coverage for a complete description of plan benefits, exclusions, limitations and conditions of coverage. Plan features and availability may vary by service area.

    About UVA Health System

    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in America and America's Top Doctors.

  • Exercise Discovery Could Save Lives of Sickest, Most Gravely Injured

    A new discovery about how exercise helps protect us from disease could one day dramatically reduce the death rate among the sickest and most gravely injured.

    People suffering from severe trauma or the full-body infection known as sepsis often develop multiple organ dysfunction syndrome, or MODS. It’s as though the immune system turns against the patient, attacking the vital organs instead of the infection. MODS is a primary cause of death in intensive care units, killing up to 80 percent of patients who develop it. Frustratingly, doctors know little about why it occurs, and nothing can be done to stop it. But the new discovery from the University of Virginia School of Medicine could change that.

    “This data suggests if everything is true, if this can indeed provide protection against sepsis and multi-organ dysfunction, that would imply that 80 percent of deaths in the clinical ICU could be cut in half,” said UVA researcher Zhen Yan, PhD.

    Exercise for Disease Prevention

    Yan’s research in mice suggests that skeletal muscles naturally make an antioxidant that helps get rid of excessive free radicals, unstable atoms that can damage cells. The antioxidant, known as EcSOD, is one of the mechanisms by which exercise protects the body from disease, his findings show. “This data really provides direct evidence that a humoral factor, a factor carried in the blood circulation produced by the largest organ of the body, ‘knows’ intelligently where to go and really provides protection where there is crisis,” said Yan, of UVA’s Department of Medicine and UVA’s Robert M. Berne Cardiovascular Research Center.  

    The antioxidant helps prevent MODS by protecting the first line of defense, the vessel wall, and preventing inflammatory cells from accumulating inside the vital organs. “In the condition of sepsis and severe trauma, our defense system becomes exaggerated to the point that [the body’s immune defenses] misunderstand the signal, so that they begin to attack the organs,” Yan said. “Our body is mistakenly thinking there is a danger signal coming from the organs themselves.”

    The new insight into the role of this elegant antioxidant that is produced by our body may let doctors rein in the excessive and damaging immune response. “If we understand the mechanism, we may be able to strategically and intelligently design better pharmacological interventions and genetic interventions,” Yan said.

    “Clinically, this has huge implications, indicating the importance of regular exercise in keeping us more resistant to many disease conditions,” he noted. “Even under the condition of serious disease, like sepsis, you have a better chance to survive.”

    Benefits for Patients, Troops

    Yan, a top expert in the study of the benefits of exercise, said his findings may offer a way to head off MODS and sepsis if those conditions are caught early. It’s unclear if a treatment based on the finding would help those with severe multi-organ dysfunction, he said. But he can foresee another benefit as well: “It could have tremendous implications for personnel deployed to the battlefield who may get injured,” he said. “If we train them regularly with the appropriate exercise regimen which will produce more [of the antioxidant] from the muscle, or we can design ways to provide biologically active EcSOD to subjects who are either vulnerable or who have already started to have severe disease conditions, this may lead to a huge impact on their survival.”

    Findings Published

    The researchers have published their findings online in the scientific journal Free Radical Biology & Medicine. The paper was authored by Jarrod A. Call, Jean Donet, Kyle S. Martin, Ashish K. Sharma, Xiaobin Chen, Jiuzhi Zhang, Jie Cai, Carolina A. Galarreta, Mitsuharu Okutsu, Zhongmin Du, Vitor A. Lira, Mei Zhang, Borna Mehrad, Brian H. Annex, Alexander L. Klibanov, Russell P. Bowler, Victor E. Laubach, Shayn M. Peirce and Yan.

    The work was supported by the National Institutes of Health, grant R01GM109473, and the American Heart Association.

    To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • Susan G. Komen Awards UVA $450,000 for Innovative Breast Cancer Research

    Researcher Melanie Rutkowski, PhD, can envision a day when doctors prescribe a specific diet to prevent the spread of breast cancer. A day when doctors could identify women at high risk for breast tumors just by examining the bacteria in their guts.

    And now Susan G. Komen has awarded her $450,000 to fund pioneering research that could make that happen.

    Over the next three years, the grant will let Rutkowski, of the University of Virginia School of Medicine, expand our understanding of the relationship between the microbiome – the microorganisms that naturally live in our bodies – and the immune system’s response to breast cancer. She will seek to determine if chronic disruption of the microbiome, possibly caused by diets heavy in processed foods, fats and sugar, is hurting the immune system’s ability to battle breast tumors – and perhaps even facilitating the cancer’s spread through the body.

    “One of the underlying questions about breast cancer is why do some individuals with breast cancer develop more aggressive or metastatic disease? And why is there so much variability in the context of how their immune systems respond to these cancers?” said Rutkowski, of the UVA Cancer Centerand UVA’s Carter Immunology Center. “What our research is suggesting is that these microbes that live within us, when they are unbalanced, they can dramatically influence disease progression, making the tumors more aggressive and ultimately result in the inability of the immune system to eliminate the tumor.”

    Breast Cancer’s Link to the Gut

    Doctors are increasingly realizing the importance of the microbiome in human health and disease, Rutkowski noted. “It’s becoming more and more appreciated now that these microbes are involved in a whole variety of different pathologies,” she said. “There have been links with neurological disorders, with certain metabolic disorders, and now there’s a lot of appreciation of how these microbes, especially within the gastrointestinal tract, influence the immune response against certain types of cancer.”

    Once breast cancer has spread, it is untreatable, so preventing its spread – known as metastasis – is vital. Rutkowski’s research suggests that manipulating the microbiome may lead to better outcomes. It could be as simple as a doctor instructing a patient to eat a diet high in fiber to complement her treatment regimen, Rutkowski said.

    “These microorganisms have many functions. They provide a first line of defense against invading pathogens, they are involved in aiding in digestion, they have a lot of metabolic products that they secrete that help to break down the food we ingest,” she said. “Those metabolic products actually have immune regulatory activity. They help to maintain the balance of good inflammation and bad inflammation, and what is becoming really appreciated about these microorganisms is that they are able to influence our immune system. Our interest, then, is to understand how they influence cancer.”

    That understanding could then be put to use in the war against breast cancer – leading to better treatments and better ways to identify women at risk, Rutkowski hopes. “Ultimately,” she said, “I’d like to see this work benefit patients.”

    About Susan G. Komen

    Susan G. Komen has invested more than $920 million to support pioneering research around the world since its founding in 1982. The group is committed to supporting research, people and resources that will reduce breast cancer deaths in the United States by 50 percent by 2026.


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

    About UVA Cancer Center
    UVA Cancer Center is accredited by the Commission on Cancer and is one of 69 National Cancer Institute (NCI) designated cancer centers in the U.S. for its work in cancer research, prevention, detection and treatment. UVA Cancer Center provides comprehensive, world-class cancer treatment in an environment of caring for patients across Virginia, led by doctors who have been honored by publications such as Best Doctors in America® and America’s Top Doctors®.

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