| Clinical Research Branch |
Intramural Program Investigators ^ Home ^ |
| Shari M. Ling, M.D., Staff Clinician Translational Research and Medical Services Section |
 Dr. Ling received her bachelor's degree from the University of Santa Clara, and her master's degree in Direct Service from the Ethel Percy Andrus School of Gerontology at the University of Southern California. She received her M.D. degree from Georgetown University, where she was elected into the AOA honor society. She completed her internship and residency in Internal Medicine at Georgetown University Medical Center, and served a year as Chief Resident in the Department of Medicine at Georgetown University. She subsequently completed a fellowship in Rheumatology at Georgetown University, and a second fellowship in Geriatric Medicine at Johns Hopkins University. She joined the Laboratory of Clinical Investigation in 2000, and transferred to the Clinical Research Branch in 2003.Research Interests: Osteoarthritis, Mobility Function, Inflammation and Aging. |
| Osteoarthritis: Osteoarthritis (OA) is a painful, chronic, progressive illness for which available therapies remain palliative. OA has been thought of as a disease limited to cartilage degeneration that progressed slowly, resulting in functional limitations late. Our research objectives are to identify early indicators of arthritis development, progression and arthritis-associated functional limitations as a prelude to the development of interventions capable of effectively modifying the disease and preserving mobility function. |
| Musculoskeletal Aging, Arthritis and Functional Limitations: The Baltimore Longitudinal Study of Aging (BLSA) represents a study of normative aging through which knees, hands, bone quality and body composition have been assessed periodically in some participants over the years using conventional radiography, single then dual photon xray absorptiometry respectively. In close collaboration with the investigators in the Longitudinal Studies Section (LSS) of the Clinical Research Branch, we have integrated validated and clinically relevant standardized questionnaires, physical examination and state-of-the-art imaging techniques that will be applied to all eligible BLSA participants. These efforts will allow us to document the process of musculoskeletal aging and delineate the transition from normal aging to the development of common musculoskeletal conditions (i.e. arthritis and osteoporosis) in healthy elderly, but also progression of disease. |
| Functional limitations are a known consequence of OA, but had been thought of as a late complication. In close collaboration with LSS investigators, we will be able to uniquely delineate the effects of musculoskeletal aging (muscles, bones, and joints) and diseases on mobility biomechanics and function, in the context of other aging body systems and diseases. In collaboration with colleagues at the Johns Hopkins University investigators of the Women's Health and Aging Study, we previously demonstrated that even well-functioning women with OA are more likely to report functional limitations that women without OA. We also observed that functional limitations were associated with lower knee extensor strength, higher body weight, and greater pain severity, but were previously not able to determine which came first. We recently reported the results of the longitudinal data acquired from the Women's Health and Aging Study II (ages 70-79 years) who initially reported no lower extremity limitation (e.g., difficulty walking one-quarter mile) or difficulty in activities of daily living (ADL; e.g., transferring) and were observed over 72 months for transitions to categories of greater functional limitations. Lower extremity OA, higher body mass index, and lower knee extensor strength independently increased the risk of transition to combined lower extremity and ADL difficulty first over 72 months. Two modifiable factors, higher relative weight and lower knee extensor strength, substantially affected these transitions, and therefore warrant increased attention in the management of lower extremity OA. |
| Inflammation: Aging is accompanied by a pro-inflammatory state expressed by the increasing levels of inflammatory cytokines, including interleukin-6 (IL- 6), tumor necrosis factor alpha (TNF-a) and interleukin- 1beta (IL-1b). At the same time, aging is associated with a decrease in serum testosterone (T) levels. In close collaboration with LSS investigators of the BLSA, systematic evaluation of these and other inflammatory markers has been integrated into the parent study. These markers will allow us to investigate their relevance to musculoskeletal aging and age-associated disease states. |
| Arthritis and Inflammation: Inflammation is known to contribute to the painful symptoms of arthritis, but vary in its severity depending on the kind of arthritis. We are studying three different forms of arthritis. As mentioned above, osteoarthritis is the most common form of arthritis. Because obesity and excess weight are known risk factors for OA development and are also associated with high inflammatory markers, we are collaborating with members of the Johns Hopkins Arthritis Center to determine the extent to which inflammation changes as overweight or obese adults with arthritis lose weight, and also whether inflammatory markers might predict the success of weight-reduction efforts. We are also interested in rheumatoid arthritis - a systemic disease that causes progressive destruction of all joints as well as progressive muscle wasting, osteoporosis and cardiovascular disease. Since inflammation may be attenuated by the autonomic nervous system, we have initiated a study of a cohort of patients with rheumatoid arthritis (RA) to determine the associations between inflammatory factors, hormonal homeostasis and autonomic nervous system function as measured by heart rate variability in collaboration with our colleagues at the Johns Hopkins Arthritis Center. Finally, we have initiated a study of polymyalgia rheumatica (PMR) - an intensely inflammatory condition that preferentially affects older adults with the sudden development of pain and stiffness of the shoulder and hip joints although clinically distinct from OA and RA. We are using PMR as a natural model of the effects of acute and systemic inflammation on drug metabolism and anemia. |
| Arthritis and Muscle Malfunction: We have initiated several studies that test the hypothesis that inflammation contributes to OA development, progression and disability. We initiated a clinical study to determine whether muscle strength, mass and function are important determinants of mobility function in adults with knee OA, and if these characteristics are associated with local inflammatory factors and circulating biomarkers. We are recruiting adults 50 years and older with and without osteoarthritis of the knee of comparable age, body weight and physical activity level. Muscle strength, muscle mass and mobility function will be correlated with biomarkers, and compared between the two groups. We are striving to complete our enrollment of 88 participants by the end of next year. Since knee OA risk is substantially increased following surgical removal of the knee meniscus, we will also be studying the inflammatory response and its contribution to muscle malfunction in patients who undergo arthroscopic removal of damaged meniscus. |
| Summary: These observational studies comprise a critical step towards the development of specific interventions capable of directly and effectively counteracting the putative factors responsible for the deleterious consequences of aging on the musculoskeletal system and age-associated diseases. |
| Contact Information: Clinical Research Branch Harbor Hospital 3001 Hanover Street Baltimore, MD 21225 Phone 410-350-3934 E mail lingsh@grc.nia.nih.gov For more information about the Branch: http://www.grc.nia.nih.gov/branches/crb/crb.htm |
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