Demography

George Sutphin, PhD, studies the molecular basis of aging. Individual age is the primary risk factor for the majority of the top causes of death in the United States and other developed nations. As our population grows older, aging is increasingly a central problem for both individual quality of life and the economics of societal health. Understanding the molecular architecture that drives aging will reveal key intervention points to extend healthy human lifespan, simultaneously delay onset of multiple categories of age-associated disease, and develop targeted treatments for specific pathologies. The Sutphin Lab uses a combination of systems biology, comparative genetics, and molecular physiology to identify new genetic and environmental factors in aging and characterize their molecular role in age-associated disease. Keywords: Aging/Age-Related Disease, Comparative Genetics, Systems Genetics

Kristen Pogreba Brown, Ph.D., M.P.H., is an assistant professor of epidemiology at the University of Arizona Mel and Enid Zuckerman College of Public Health. Prior to joining the faculty, Dr. Pogreba-Brown was an Epidemiologist with the College as the director of the Student Aid for Field Epidemiology Response (SAFER) team. In addition to continuing to oversee the SAFER program, her research projects are focused on foodborne diseases and improving methodology to respond to outbreak investigations. She is currently working on a project to identify the risk factors related to foodborne infection as well as the risk factors related to specific chronic outcomes following acute disease. She has recently initiated a One Health Program at the University to form collaborative research teams from across campus and develop a graduate level certificate program. She is also actively involved in public health preparedness activities, specifically for large events. Dr. Pogreba-Brown works with various county health departments in Arizona as well as the state health department to aid in outbreak investigations and serves on the state’s Foodborne Taskforce Committee.

My research program lies in one more focused and two broad and interconnected areas of aging research and intervention. a. Infection and immunity with aging. Over the past 15 years my group has systematically investigated alterations with aging of the immune system and its interactions with acute and persistent microbial pathogens. In the process, we have discovered and described multiple and cumulative defects in microbial detection, initial recognition and uptake by the innate immune system, processing, presentation and initiation of the adaptive immune response, generation of effector immunity and of memory responses and homeostasis and long-term regulation of lymphocyte subsets. We have followed up that work with attempts to correct molecular and cellular defects using novel vaccination and thymic rejuvenation models in mice and non-human primates, and by validating the observations from these models in humans, as well as deriving primary data from human subjects on these same topics. . There is no doubt that I will continue this work on both tracks: primary, basic research will be performed in the mouse, human or NHP model, and, depending on suitability, may be also validated in other models. Translation will be performed in human or NHP models, where we will seek to intervene therapeutically to improve outcomes of infection in older adults. The ultimate goal for the next decade of my career and beyond will be to produce palpable improvement in the immune system of older adults so as to increase success of vaccination and resistance to infection. b. Inflammation in aging: causes and consequences. This is a broader interest of mine, that intersects not only with the immune system, but also with microbial colonization, gut barrier function, metabolism, adiposity and energy sensing. Why do older adults exhibit increased signs and markers of systemic inflammation? Is this inflammation multifactorial, or does it lie in an overexcitable immune system, or increased proinflammatory adipose mass or altered microbial colonization and increased permeability of different (mostly mucosal) barriers? Or a combination thereof? Can we conclusively intervene against diseases of aging and, perhaps, normal aging itself, by modulating inflammation? Microbiome sequencing, deliberate colonization with specific microflora, depletion of different immune cell subsets and/or antibiotic and anti-inflammatory treatments as well as metabolic intervention will all be combined to understand and treat these conditions and their impact upon aging. c. Interventions to extend healthspan and longevity. Advances in the biology of aging have now reached the point where it is no longer unrealistic to put the incredible promise of health-prolonging anti-aging intervention to use in humans. One must: (i) understand effects of life extension in model organisms upon healthspan and end organ function; (ii) carefully dissect signaling pathways that lead to the measured outcomes and validate them in higher primates or humans; and (iii) intervene along these pathways to apply life and healthspan extension treatments. We are currently in the process of multidisciplinary collaborative studies to understand end-organ function and quality of life in the course of different mTOR pathway manipulations in adult and aged mice. Drug discovery program will follow to optimize treatments, and translation will be attempted subsequently in primates and humans.

Yann C. Klimentidis, PhD, is an Associate Professor in the Department of Epidemiology and Biostatistics in the Mel and Enid Zuckerman College of Public Health at the University of Arizona. His research centers on improving our understanding of the links between genetic variation, lifestyle factors, metabolic disease, and health disparities. In the past, he has used measures of genetic admixture and genomic tests of natural selection to understand the genetic basis of population differences in disease susceptibility. His most recent work examines the use various statistical approaches for the analysis of high-dimensional genetic data for improving prediction of genetic susceptibility to type-2 diabetes. In addition, his work examines gene-by-lifestyle interactions in type-2 diabetes, as well as understanding the causal links between metabolic traits such as dyslipidemia and type-2 diabetes. Keywords: Genetics, epidemiology, Cardiometabolic disease, Physical activity

Nearly 50 million couples experience some form of infertility worldwide. Several factors increase a woman’s risk for infertility including aging, stress, and exposure to chemicals. A group of chemicals collectively known as phthalates have been classified as endocrine disruptors based on their ability to interact with the reproductive system. Phthalates have been detected in human urine, animal tissues, and feed. Despite these observations, how phthalates interact with the female reproductive system and what this means for overall fertility is currently unknown. Dr. Craig's work focuses on understanding how phthalates affect the function of the ovary, the major reproductive organ in females. Thus, work in her laboratory is focused on using animal models to help us understand the mechanisms by which phthalates exert their effects on the ovary, determine whether phthalates cause female infertility, and examine whether the effects of phthalates on female reproduction can be prevented or reversed. Using this knowledge she hopes to inspire and guide future work aimed at reducing, preventing, and/or reversing chemical-related infertility in humans and animals. Keywords: Infertility, Toxicology, Endocrine Disruptors, Phthalates, Reproduction