Age-Related Adverse Inflammatory and Metabolic Changes Begin Early in Adulthood.
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2018-05-22
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Abstract
Aging is characterized by deleterious immune and metabolic changes, but the onset of these changes is unknown. We measured immune and metabolic biomarkers in adults beginning at age 30. To our knowledge, this is the first study to evaluate these biomarkers in adults aged 30 to over 80. Biomarkers were quantified in 961 adults. Tumor necrosis factor alpha (TNF-α), tumor necrosis factor receptor I (TNFR-I), tumor necrosis factor receptor II (TNFR-II), interleukin (IL)-2, IL-6, VCAM-I, D-Dimer, G-CSF, regulated on activation, normal T cell expressed and secreted (RANTES), matrix metalloproteinase-3 (MMP-3), adiponectin, and paraoxonase activity were measured by ELISA. Acylcarnitines and amino acids (AAs) were measured by mass spectrometry and reduced to a single factor using principal components analysis (PCA). Glycine was analyzed separately. The relationship between age and biomarkers was analyzed by linear regression with sex, race, and body mass index (BMI) as covariates. Age was positively correlated with TNF-α, TNFR-I, TNFR-II, IL-6, IL-2, VCAM-1, D-Dimer, MMP-3, adiponectin, acylcarnitines, and AAs. Age was negative correlated with G-CSF, RANTES, and paraoxonase activity. BMI was significant for all biomarkers except IL-2, VCAM-1, RANTES, paraoxonase activity, and the AA factor. Excluding MMP-3, greater BMI was associated with potentially adverse changes in biomarker concentrations. Age-related changes in immune and metabolic biomarkers, known to be associated with poor outcomes in older adults, begin as early as the thirties.
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Scholars@Duke
Daniel Christopher Parker
My clinical and research interests center on the development and use of disease-modifying treatments for Alzheimer's disease and related dementias (ADRD). I am a regional leader in the use of amyloid targeted therapies (ATT), including lecanemab and donanemab, for the treatment of early Alzheimer's disease. I serve as director of the Duke Memory Disorders Clinic.
Carl F. Pieper
Analytic Interests.
1) Issues in the Design of Medical Experiments: I explore the use of reliability/generalizability models in experimental design. In addition to incorporation of reliability, I study powering longitudinal trials with multiple outcomes and substantial missing data using Mixed models.
2) Issues in the Analysis of Repeated Measures Designs & Longitudinal Data: Use of Hierarchical Linear Models (HLM) or Mixed Models in modeling trajectories of multiple variables over time (e.g., physical and cognitive functioning and Blood Pressure). My current work involves methodologies in simultaneous estimation of trajectories for multiple variables within and between domains, modeling co-occuring change.
Areas of Substantive interest: (1) Experimental design and analysis in gerontology and geriatrics, and psychiatry,
(2) Multivariate repeated measures designs,
Virginia Byers Kraus
Virginia Byers Kraus, MD, PhD, is the Mary Bernheim Distinguished Professor of Medicine, Professor of Orthopaedic Surgery, Professor of Pathology and a faculty member of the Duke Molecular Physiology Institute in the Duke University School of Medicine. She is a practicing Rheumatologist with over 30 years’ experience in translational musculoskeletal research focusing on osteoarthritis, the most common of all arthritides. She trained at Brown University (ScB 1979), Duke University (MD 1982, PhD 1993) and the Duke University School of Medicine (Residency in Internal Medicine and Fellowship in Rheumatology). Her career has focused on elucidating osteoarthritis pathogenesis and translational research into the discovery and validation of biomarkers for early osteoarthritis detection, prediction of progression, monitoring of disease status, and facilitation of therapeutic developments. She is co-PI of the Foundation for NIH Biomarkers Consortium Osteoarthritis project. Trained as a molecular biologist and a Rheumatologist, she endeavors to study disease from bedside to bench.
William Erle Kraus
My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation. My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I practice as a preventive cardiologist with a focus on cardiometabolic risk and exercise physiology for older athletes. My research space has both a basic wet laboratory component and a human integrative physiology one.
One focus of our work is an integrative physiologic examination of exercise effects in human subjects in clinical studies of exercise training in normal individuals, in individuals at risk of disease (such as pre-diabetes and metabolic syndrome; STRRIDE), and in individuals with disease (such as coronary heart disease, congestive heart failure and cancer).
A second focus of my research group is exploration of genetic determinates of disease risk in human subjects. We conduct studies of early onset cardiovascular disease (GENECARD; CATHGEN), congestive heart failure (HF-ACTION), peripheral arterial disease (AMNESTI), and metabolic syndrome. We are exploring analytic models of predicting disease risk using established and innovative statistical methodology.
A third focus of my group’s work is to understand the cellular signaling mechanisms underlying the normal adaptive responses of skeletal muscle to physiologic stimuli, such as occur in exercise conditioning, and to understand the abnormal maladaptive responses that occur in response to pathophysiologic stimuli, such as occur in congestive heart failure, aging and prolonged exposure to microgravity.
Recently we have begun to investigate interactions of genes and lifestyle interventions on cardiometabolic outcomes. We have experience with clinical lifestyle intervention studies, particularly the contributions of genetic variants to interventions responses. We call this Lifestyle Medicopharmacogenetics.
KEY WORDS:
exercise, skeletal muscle, energy metabolism, cell signaling, gene expression, cell stretch, heart failure, aging, spaceflight, human genetics, early onset cardiovascular disease, lifestyle medicine
Olga Ilkayeva
Olga Ilkayeva, Ph.D., is the Director of the Metabolomics Core Laboratory at Duke Molecular Physiology Institute. She received her Ph.D. training in Cell Regulation from UT Southwestern Medical Center at Dallas, TX. Her postdoctoral research in the laboratory of Dr. Chris Newgard at Duke University Medical Center focused on lipid metabolism and regulation of insulin secretion. As a research scientist at the Stedman Nutrition and Metabolism Center, Dr. Ilkayeva expanded her studies to include the development of targeted mass spectrometry analyses. Currently, she works on developing and validating quantitative mass spectrometry methods used for metabolic profiling of various biological models with emphasis on diabetes, obesity, cardiovascular disease, and the role of gut microbiome in both health and disease.
James R. Bain
Harvey Jay Cohen
Dr. Cohen's research program includes clinical research relating to aspects of the pathways to functional decline and reilience with aging, geriatric assessment, and cancer and anemia in the elderly.
Pathways to functional decline are being explored through the NIA funded Claude Pepper Older Americans Independence Center, and includes studies of the contributions of age related physiologic change, in particular changes in inflammatory parameters, comorbid diseases and conditions, environment, genetics, and the interactionas among them. Data are derived from several current studies as well as previously collected data sets from the Established Populations for Epidemiologic Studies of the Elderly (EPESE), National Long Term Care Survey, and the Chinese Longevity Study (with Dr. Zeng Yi). Previous work has demonstrated the important contributions of age related inflammation and coagulation activation to functional status. He is Co-PI of the Pepper Center Physical Performance Across the LifeSpan (PALS) study, which is a longitudinal cohort study of community dwelling adults from age 30-90+and includes functional measures and biomarkers on inflammation and metabolism.
Geriatric assessment approaches have been studied in a number of randomized and controlled studies and work is now concentrating on the application of Comprehensive Geriatric Assessment tools to the evaluation and treatment of elderly patients with cancer. This is an extension and continuation of a long standing interest in geriatric oncology. Previous studies have elucidated age-related patterns of disease presentation, treatment approaches, clinical trials, survivorship, quality of life, impact of comrobidities and functional outcomes. Dr. Cohen was co-chair, and now member of the Cancer in the Older Adult Committee of the Alliance for Clinical Trials in Oncology (ALLIANCE). A number of active studies and ongoing data bases aree being utilized to address these questions.
Anemia in the older adult is being addressed through an NIA funded U01 consortium (Dr. Cohen Co-PI). the current main study is an observational study followed by a pragmatic treatment trial for anemia in older adults with CHF, in collaboration with the Cardiovascular Research Network (CVRN) of the Health services research network (HSRN)
Miriam C. Morey
The general focus of Dr. Morey's work is exercise and aging. All of her research examines how physical activity, exercise training, or physical fitness influence the physical functioning and/or pyschosocial quality of life of older adults. She directs a supervised hospital-based program for older adults, which is used to examine longitudinally the effects of exercise training on the musculoskeletal, articular, and cardiorespiratory systems. Furthermore, she has a number of studies that examine how system-wide impairments serve as preclinical indicators of disability and overall decline in the quality of life of older adults. Ongoing studies examine the role of exercise training in attenuation or reversal of functional decline and examination of the effectivenes of different methods of physical activity counseling for home-based exercise.
Dr. Morey's research evolves directly from three sources: (1) primary analyses of clinical trials regarding the impact of exercise on a specific outcome, (2) longitudinal analyses of participants in ongoing clinical exercise programs, and (3) secondary analyses of clinical trials which involve exercise or physical activity.
Although physical activity and exercise are the interventions of interest in all of these studies, the outcomes of interest vary considerably. Within the broad domain of aging, Dr. Morey has examined the impact of exercise on physical performance, well-being, sleep quality, disability, and functional limitations. More recently, Dr. Morey has several studies focusing on the effect of tailored telephone physical activity counseling to improve function in elders. Specific studies are targeted to newly diagnosed cancer survivors, long-term cancer survivors, and frail elders in geriatric and primary care settings.
Dr. Morey's expertise is in the area of exercise physiology and aging. She has specific knowledge in age-related changes in cardiorespiratory functioning, the effects of habitual exercise (longitudinal) on performance, and exercise programming for older adults.
Key Words: Exercise, maximal oxygen uptake, cardiorespiratory fitness, aging, disability,
functional limitations, longitudinal
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