Allostatic Load, Senescence, and Aging Among Japanese Elderly Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Rachael Elizabeth Leahy, M.Sc. Graduate Program in Anthropology The Ohio State University 2014 Dissertation Committee: Dr. Douglas E. Crews, Advisor Dr. Jeffrey Cohen Dr. Randy Nelson Copyright by Rachael Elizabeth Leahy 2014 2 Abstract Senescence varies substantially within and among populations. Data examined here extend knowledge on modern human variation by analyzing elders from Nagasaki Prefecture, Japan, enhance our understanding of relationships between senescence and human biology, and provide more information concerning the use of allostatic load (AL) as a measure of senescent decline among a non-Western population. Developing a valid method for assessing physiological variation due to senescence will benefit those studying health outcomes and survival of elders. It also will aid in focusing healthcare funds and interventions by targeting those most likely to experience unwanted outcomes. Understanding how Japan’s elders are surviving and adapting to old age, life-long stress, and developing dysfunction with increasing age provides a model of how others may slow senescence in other settings. Background: 96 elderly residents of Sakiyama City, Nagasaki Prefecture (ages 55-89) and 27 elderly residents of Hizen-Oshima, Nagasaki Prefecture, Japan (ages 51- 82) were sampled for components of allostatic load (AL) and other aspects of physical and physiological variation. Surveys were conducted by local health care nursing staff and members of a joint American-Japanese research team during participants’ yearly physical examinations. Japan was selected as the study site because Japanese men and ii women rank among the longest-lived people in the world and the population is relatively genetically homogenous. Methods: AL is a summary measure of physiological activity across multiple regulatory systems pertinent to disease risks. AL incorporates data on ten components: systolic and diastolic blood pressure, high density lipoproteins, total cholesterol, glycosylated hemoglobin, dihydroepiandrosterone-sulfate, cortisol, noradrenaline, adrenaline, and waist:hip ratio. It is calculated by summing the number of components for which an individual’s values are in the highest risk quartile. Two alternate measures of AL were calculated for comparison. The first used decile as opposed to quartile cut- points. The second was constructed using principal components analysis (ALPC1). Multivariate regressions were used to analyze associations between AL, controlling for age and sex, and physiological variables in each sample. Results: AL was higher among men than women and was poorly associated with age. Multivariate models of AL, sex, and age predict GTP, creatinine, white blood cell count, percent body fat, weight, dopamine, red blood cell count, GPT, and blood glucose variably by location. Associations between AL and physiological variables change when quartile vs. decile cut-points were used to construct the measure. ALPC1 showed significant associations in the Sakiyama sample with GPT, GTP, white blood cell count, creatine, dopamine, hematocrit, hemoglobin, red blood cell count, uric acid, and the self maintenance score of the Tokyo Metropolitan Institute of Gerontology Index of Competency. iii Conclusions: The poor association between AL and age suggests AL may be assessing underlying senescence better than age alone. Higher AL indicates men in this sample experienced greater cumulative physiological and physical stress over their lives as compared to women in this Japanese setting. AL is significantly associated with immune, liver, and renal function, and aspects of frailty. These results provide additional support for suggesting AL measures physiological dysregulation and senescent decline across multiple somatic systems. Results from ALPC1 indicate sex is an important component in AL. iv Dedication Dedicated to my family: Nancy and Glenn Leahy, for realizing that Dr. Shelly was more than a childhood fantasy and for supporting my dream every step of the way Sarah Leahy Dore, for always being my role-model and my inspiration v Acknowledgements This dissertation could not have been completed without assistance from many people. First, I thank my advisor, Dr. Douglas E. Crews, for his direction, support, and encouragement from my first year at The Ohio State University through the end of the dissertation process. Dr. Crews has spent countless hours reading and re-reading this manuscript and many others; for his tireless efforts to make me into a better scientist, I thank him gratefully. I would also like to thank the team of researchers in Japan who, with my advisor, carefully collected these data: Yosuke Kusano, Kiyoshi Aoyagi, Takahiro Maeda, Aiko Iwamoto, and especially Dr. Yoshiaki Sone. My other committee members, from my candidacy examination through to the dissertation, have also been helpful: Dr. Clark Larsen, Dr. Randy Nelson, and Dr. Jeffrey Cohen. I also thank my research assistants for their support and hardwork: Katie Duff and Jenny Ahern. I would also like to give special thanks to the residents of and participants from Sakiyama and Hizen-Oshima without whom this study would not have been possible. I would like to thank my family, Nancy and Glenn Leahy, and Sarah and Chris Dore for the tremendous support they have given me throughout graduate school. Finally, I would like to thank Kraig Frederickson for his love and and unwavering support of all my endeavors. vi Vita 2007........................................A.B. Anthropology, Bowdoin College 2009........................................M.Sc. Anthropologie Biologique, Préhistoire, et Paléoanthropologie, Université Bordeaux I: Science et Technologies 2010-2014 ..............................Susan L. Huntington Dean’s Distinguished Fellow, The Ohio State University 2012-2013 ..............................Graduate Teaching Associate, The Ohio State University Publications Andre A., R. Leahy, and S. Rottier. 2013. Cremated human remains deposited in two phases: Evidence from the necropolis of the Tuileries Site (Lyon, France: 2nd century AD). International Journal of Osteoarchaeology. http://onlinelibrary.wiley.com/doi/10.1002/oa.2317/abstract. Leahy R. 2012. Diagnoses sexuelles primaires et secondaires [Primary and secondary sexual diagnoses]. In Rottier S, Piette J, Mordant C, eds. Archéologie funéraire du Bronze final dans les vallées de l'Yonne et de la haute Seine. Les nécropoles de Barbey, Barbuise et La Saulsotte. Dijon, Editions Universitaire de Dijon. Leahy R. and D.E. Crews. 2012. Physiological dysregulation and somatic decline among elders: Modeling, applying, and re-interpreting allostatic load. Collegium Antropologicum 36(1):11-22. vii Publications Deguilloux M.F., S. Rottier, R. Leahy, and M.H. Pemonge. 2012. European neolithization and ancient DNA: an assessment. Evolutionary Anthropology 21:24-37. Deguilloux M.F., S. Ricaud, R. Leahy, and M.H. Pemonge. 2011. Analysis of ancient human DNA and primers contamination: One step backward one step forward. Forensic Science International 210(1-3):102-109. Fields of Study Major Field: Anthropology viii Table of Contents Abstract ............................................................................................................................... ii Dedication ........................................................................................................................... v Acknowledgements ............................................................................................................ vi Vita .................................................................................................................................... vii Chapter 1: Introduction ....................................................................................................... 1 1.1 Introduction ............................................................................................................... 1 1.2 Theories of Senescence ............................................................................................. 3 1.2.1 Non-evolutionary theories of senescence ........................................................... 4 1.2.2 Evolutionary theories of senescence ................................................................... 8 1.3 Studying Senescence ............................................................................................... 13 1.3.1 Demographic Transition ................................................................................... 13 1.4 Stress, Stressors, and Stress Responses ................................................................... 16 1.4.1 Defining Stress ................................................................................................. 16 1.4.2 Stressors ............................................................................................................ 19 1.4.3 Measuring Stress Responses ............................................................................. 20 1.4.4 Neuroendocrinology of Stress .......................................................................... 24 1.4.5 Stress and anthropology.................................................................................... 26 1.5 Project Objectives and Hypotheses ......................................................................... 28 1.5.1