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

This renewal will provide detailed information on infectious disease and immune responsiveness over the life course in a pre-modern population of forager-horticulturalists of South America experiencing a high pathogen burden. Investigation of immune system development and senescence in a large sample of older adults can reveal unique insights about how the immune system responds to the intensity of pathogen exposure and how increased activation of the immune system throughout life can affect the rate of immunosenesence. Since much of the world still lives in developing countries, with co-infection of parasites, viruses and bacteria, the results of this research, combined with measures of aging and disease in other populations such as the U.S. and Indonesia, will help eludicate trends in disease epidemiology across environmental and social contexts.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG024119-07S2
Application #
8188275
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
2011-09-01
Budget End
2012-08-31
Support Year
7
Fiscal Year
2011
Total Cost
$602,676
Indirect Cost
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
Blackwell, Aaron D; Urlacher, Samuel S; Beheim, Bret et al. (2017) Growth references for Tsimane forager-horticulturalists of the Bolivian Amazon. Am J Phys Anthropol 162:441-461
Stieglitz, Jonathan; Trumble, Benjamin C; Kaplan, Hillard et al. (2017) Horticultural activity predicts later localized limb status in a contemporary pre-industrial population. Am J Phys Anthropol 163:425-436
Gurven, Michael; Fuerstenberg, Eric; Trumble, Benjamin et al. (2017) Cognitive performance across the life course of Bolivian forager-farmers with limited schooling. Dev Psychol 53:160-176
Kaplan, Hillard; Trumble, Benjamin C; Stieglitz, Jonathan et al. (2017) Diet, atherosclerosis, and helmintic infection in Tsimane - Authors' reply. Lancet 390:2035
Jaeggi, Adrian V; Kramer, Karen L; Hames, Raymond et al. (2017) Human grooming in comparative perspective: People in six small-scale societies groom less but socialize just as much as expected for a typical primate. Am J Phys Anthropol 162:810-816
Kaplan, Hillard; Thompson, Randall C; Trumble, Benjamin C et al. (2017) Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet 389:1730-1739
Trumble, Benjamin C; Stieglitz, Jonathan; Blackwell, Aaron D et al. (2017) Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. FASEB J 31:1508-1515
Gurven, Michael; Stieglitz, Jonathan; Trumble, Benjamin et al. (2017) The Tsimane Health and Life History Project: Integrating anthropology and biomedicine. Evol Anthropol 26:54-73
Sobolewski, Marissa; Weiss, Bernard; Martin, Melanie et al. (2017) Toxicoanthropology: Phthalate exposure in relation to market access in a remote forager-horticulturalist population. Int J Hyg Environ Health 220:799-809
Gurven, Michael D; Trumble, Benjamin C; Stieglitz, Jonathan et al. (2016) Cardiovascular disease and type 2 diabetes in evolutionary perspective: a critical role for helminths? Evol Med Public Health :

Showing the most recent 10 out of 76 publications