Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm.
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2020-05-05
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Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972-1973. Rates of change in each biomarker over ages 26-38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person's pace of biological aging.
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Belsky, Daniel W, Avshalom Caspi, Louise Arseneault, Andrea Baccarelli, David L Corcoran, Xu Gao, Eiliss Hannon, Hona Lee Harrington, et al. (2020). Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm. eLife, 9. pp. 1–56. 10.7554/elife.54870 Retrieved from https://hdl.handle.net/10161/21108.
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Scholars@Duke

Avshalom Caspi
Caspi’s research is concerned with three questions: (1) How do childhood experiences shape aging and the course of health inequalities across the life span? (2) How do genetic differences between people shape the way they respond to their environments? (3) How do mental health problems unfold across and shape the life course?

Kim Marie Huffman
Determining the role of physical activity in modulating health outcomes (cardiovascular disease risk) in persons with rheumatologic diseases (rheumatoid arthritis, gout, osteoarthritis)
Integrating clinical rheumatology, basic immunology, metabolism, and exercise science in order to reduce morbidity in individuals with arthritis
Evaluating relationships between circulating and intra-muscular metabolic intermediates and insulin resistance in sedentary as well as individuals engaging in regular exercise
Addressing the role of physical activity in modulating inflammation, metabolism, and functional health in aging populations

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

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,

Terrie E. Moffitt
Terrie E. Moffitt, Ph.D., is the Nannerl O. Keohane University Professor of Psychology at Duke University, and Professor of Social Development at King’s College London. Her expertise is in the areas of longitudinal methods, developmental theory, mental disorders and antisocial behaviors, neuropsychology, and genomics in behavioral science. She is currently uncovering the consequences of a lifetime of mental and behavioral disorder on processes of aging. She is the Associate Director of the Dunedin Longitudinal Study, which follows a 1972 birth cohort in New Zealand. She also co-founded the Environmental Risk Longitudinal Twin Study (E-Risk), which follows a 1994 birth cohort in the UK. Dr. Moffitt also is a licensed clinical psychologist, with specialization in neuropsychological assessment. She collaborates with criminologists, economists, geneticists, epidemiologists, sociologists, demographers, gerontologists, statisticians, neuroscientists, medical scientists, opthalmologists, and dentists. Dr. Moffitt is a fellow of the National Academy of Medicine and the American Academy of Arts and Sciences , as well as the British Academy, Academy of Medical Sciences (UK), Academia Europa, Association of Psychological Science, and the American Society of Criminology. She holds honorary doctorates from the Katholieke Universiteit Leuven, Belgium, and Universitat Basel, Switzerland. For her research, Dr. Moffitt has received both the American Psychological Association's Early Career Contribution Award and Distinguished Career Award. Dr. Moffitt was also awarded a Royal Society-Wolfson Merit Award, the Klaus-Grawe Prize, and was a recipient of the Stockholm Prize in Criminology, NARSAD Ruane Prize, the Klaus J. Jacobs Research Prize, and in 2022 the Grawemeyer Prize. Her service includes serving as chair of the Board on Behavioral, Cognitive, and Sensory Science at NASEM, Chair of the NIA Data Monitoring Committee for the Health and Retirement Study, and Chair of the Jury for the Klaus J. Jacobs Prize in Switzerland. Dr. Moffitt attended the University of North Carolina at Chapel Hill for her undergraduate degree in psychology. She continued her training in psychology at the University of Southern California, receiving an M.A. in experimental animal behavior, and a Ph.D. in clinical psychology. She also completed postdoctoral training in geriatrics and neuropsychology at the University of California Los Angeles Neuropsychiatric Institute. In her spare time, she works on her poison-ivy farm in North Carolina.
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