The goal of this application is to test the general hypotheses that: (1) early and frequent exposure to pathogens accelerates immune system development and 'primes'the immune system to higher levels of baseline immune activity and 2) this chronic immune system activation throughout life results in more rapid immunosenescence and a decline in the ability to defend against novel pathogens.. The Tsimane are Bolivian forager-horticulturalists that live with no electricity, running water, or waste disposal, and have extremely limited access to modern medicine. To accomplish our goal, there are five specific aims of this competitive revision to the existing R01 """"""""The Human Life Course and the Biodemography of Aging"""""""".
Aim 1 is to measure the levels of cytokines, inflammatory biomarkers, and immunoglobulins in Tsimane sera.
Aim 2 is to test cytokine responses during in vitro stimulation of fresh whole-blood with bacterial, viral, and helminthic antigens.
Aim 3 is to quantify in vivo lymphocyte and T-cell populations with flow cytometry to characterize cellular components of immunity by age and sex.
Aim 4 is to test a series of predictions derived from the above two hypotheses.
Aim 5 is investigate the relationships between disease states, functional status, mortality and immune system function. The addition of this project will allow us to build a cross-sectional and longitudinal profile of a large sample of adults to model interactions between infection, immune system development and immunosenescence in a population that reached maturity in a pre-modern, highly infectious environment. We combine four methods to investigate immune responsiveness to infection: 1) physician exams combined with laboratory analysis to diagnosis infections by type;2) measurement of serum cytokines, inflammatory markers and immunoglobulins;3) In vitro whole blood challenges with common and novel helminthic, viral and bacterial antigens;4) flow cytometry to identify number and proportions of memory- and senescent- T and B cell phenotypes.). As the Tsimane are undergoing rapid change, we will also be able to assess within-population variance by examining the effects of acculturation on immunity at the community and individual level. We will also compare our results to those obtained in the U.S. and other countries, to assess the impacts of the infectious burden of disease on immunity over the life course.

Public Health Relevance

of research to public health This renewal will provide detailed information on the impacts of infectious disease on health, functional status and mortality in a pre-modern population of forager-horticulturalists of South America experiencing similar demographic conditions as those in mid-19th century Europe. Investigation of arterial, heart and kidney disease in a large sample of older adults can reveal unique insights about the relative contributions of diet, energy expenditure and inflammation due to disease on the rate of physiological aging. in all societies including the contemporary American experience. The results, combined with measures of aging and disease in other populations such as the U.S., Mexico and Indonesia, may help to explain the historical increases in life expectancy over the past several centuries.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG024119-08
Application #
8334415
Study Section
Social Sciences and Population Studies Study Section (SSPS)
Program Officer
Haaga, John G
Project Start
2004-09-15
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
8
Fiscal Year
2012
Total Cost
$1,077,693
Indirect Cost
$89,166
Name
University of California Santa Barbara
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
094878394
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106
Gurven, Michael; Costa, Megan; Ben Trumble et al. (2016) Health costs of reproduction are minimal despite high fertility, mortality and subsistence lifestyle. Sci Rep 6:30056
Hodges-Simeon, Carolyn R; Hanson Sobraske, Katherine N; Samore, Theodore et al. (2016) Facial Width-To-Height Ratio (fWHR) Is Not Associated with Adolescent Testosterone Levels. PLoS One 11:e0153083
Trumble, Benjamin C; Blackwell, Aaron D; Stieglitz, Jonathan et al. (2016) Associations between male testosterone and immune function in a pathogenically stressed forager-horticultural population. Am J Phys Anthropol 161:494-505
Stieglitz, Jonathan; Madimenos, Felicia; Kaplan, Hillard et al. (2016) Calcaneal Quantitative Ultrasound Indicates Reduced Bone Status Among Physically Active Adult Forager-Horticulturalists. J Bone Miner Res 31:663-71
Blackwell, Aaron D; Trumble, Benjamin C; Maldonado Suarez, Ivan et al. (2016) Immune function in Amazonian horticulturalists. Ann Hum Biol 43:382-96
Horvath, Steve; Gurven, Michael; Levine, Morgan E et al. (2016) An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. Genome Biol 17:171
Trumble, Benjamin C; Gaulin, Steven J C; Dunbar, Matt D et al. (2016) No Sex or Age Difference in Dead-Reckoning Ability among Tsimane Forager-Horticulturalists. Hum Nat 27:51-67
Martin, Melanie A; Garcia, Geni; Kaplan, Hillard S et al. (2016) Conflict or congruence? Maternal and infant-centric factors associated with shorter exclusive breastfeeding durations among the Tsimane. Soc Sci Med 170:9-17
Gurven, Michael D; Trumble, Benjamin C; Stieglitz, Jonathan et al. (2016) High resting metabolic rate among Amazonian forager-horticulturalists experiencing high pathogen burden. Am J Phys Anthropol 161:414-425
Jaeggi, Adrian V; Trumble, Benjamin C; Kaplan, Hillard S et al. (2015) Salivary oxytocin increases concurrently with testosterone and time away from home among returning Tsimane' hunters. Biol Lett 11:

Showing the most recent 10 out of 64 publications