Patterns of Senescence in Human Cardiovascular Fitness: Vo2 Max in Subsistence and Industrialized Populations

Objectives—This study explores whether cardiovascular fitness levels and senescent decline are similar in the Tsimane of Bolivia and Canadians, as well as other subsistence and industrialized populations. Among Tsimane, we examine whether morbidity predicts lower levels and faster decline of cardiovascular fitness, or whether their lifestyle (e.g., high physical activity) promotes high levels and slow decline. Alternatively, high activity levels and morbidity might counterbalance such that Tsimane fitness levels and decline are similar to those in industrialized populations. Methods—Maximal oxygen uptake (VO2max) was estimated using a step test heart rate method for 701 participants. We compared these estimates to the Canadian Health Measures Survey and previous studies in industrialized and subsistence populations. We evaluated whether health indicators and proxies for market integration were associated with VO2max levels and rate of decline for the Tsimane. Results—The Tsimane have significantly higher levels of VO2max and slower rates of decline than Canadians; initial evidence suggests differences in VO2max levels between other subsistence and industrialized populations. Low hemoglobin predicts low VO2max for Tsimane women while helminth infection predicts high VO2max for Tsimane men, though results might be specific to the VO2max scaling parameter used. No variables tested interact with age to moderate decline. Conclusions—The Tsimane demonstrate higher levels of cardiovascular fitness than industrialized populations, but levels similar to other subsistence populations. The high VO2max of Tsimane is consistent with their high physical activity and few indicators of cardiovascular disease, measured in previous studies

Modernization, Sexual Risk-Taking, and Gynecological Morbidity Among Bolivian Forager-Horticulturalists

Sexual risk-taking and reproductive morbidity are common among rapidly modernizing populations with little material wealth, limited schooling, minimal access to modern contraception and healthcare, and gendered inequalities in resource access that limit female autonomy in cohabiting relationships. Few studies have examined how modernization influences sexual risk-taking and reproductive health early in demographic transition. Tsimane are a natural fertility population of Bolivian forager-farmers; they are not urbanized, reside in small-scale villages, and lack public health infrastructure. We test whether modernization is associated with greater sexual risk-taking, report prevalence of gynecological morbidity (GM), and test whether modernization, sexual risk-taking and parity are associated with greater risk of GM. Data were collected from 2002–2010 using interviews, clinical exams, and laboratory analysis of cervical cells. We find opposing effects of modernization on both sexual risk-taking and risk of GM. Residential proximity to town and Spanish fluency are associated with greater likelihood of men’s infidelity, and with number of lifetime sexual partners for men and women. However, for women, literacy is associated with delayed sexual debut after controlling for town proximity. Fifty-five percent of women present at least one clinical indicator of GM (n = 377); 48% present inflammation of cervical cells, and in 11% the inflammation results from sexually transmitted infection (trichomoniasis). Despite having easier access to modern healthcare, women residing near town experience greater likelihood of cervical inflammation and trichomoniasis relative to women in remote villages; women who are fluent in Spanish are also more likely to present trichomoniasis relative to women with moderate or no fluency. However, literate women experience lower likelihood of trichomoniasis. Parity has no effect on risk of GM. Our results suggest a net increase in risk of reproductive morbidity among rapidly modernizing, resource-stressed populations

Depression as Sickness Behavior? A Test of the Host Defense Hypothesis in a High Pathogen Population

Sadness is an emotion universally recognized across cultures, suggesting it plays an important functional role in regulating human behavior. Numerous adaptive explanations of persistent sadness interfering with daily functioning (hereafter “depression”) have been proposed, but most do not explain frequent bidirectional associations between depression and greater immune activation. Here we test several predictions of the host defense hypothesis, which posits that depression is part of a broader coordinated evolved response to infection or tissue injury (i.e. “sickness behavior”) that promotes energy conservation and reallocation to facilitate immune activation. In a high pathogen population of lean and relatively egalitarian Bolivian foragerhorticulturalists, we test whether depression and its symptoms are associated with greater baseline concentration of immune biomarkers reliably associated with depression in Western populations (i.e. tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1β], interleukin-6 [IL-6], and C-reactive protein [CRP]). We also test whether greater pro-inflammatory cytokine responses to ex vivo antigen stimulation are associated with depression and its symptoms, which is expected if depression facilitates immune activation. These predictions are largely supported in a sample of older adult Tsimane (mean±SD age=53.2±11.0, range=34-85, n=649) after adjusting for potential confounders. Emotional, cognitive and somatic symptoms of depression are each associated with greater immune activation, both at baseline and in response to ex vivo stimulation. The association between depression and greater immune activation is therefore not unique to Western populations. While our findings are not predicted by other adaptive hypotheses of depression, they are not incompatible with those hypotheses and future research is necessary to isolate and test competing predictions

Cardiovascular Disease and Type 2 Diabetes in Evolutionary Perspective: A Critical Role for Helminths?

Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistencelevel human populations, and by extension prehistoric populations. Although some caveats remain, evidence shows these diseases to be unusual among well-studied hunter-gatherers and other subsistence populations with minimal access to healthcare. Here we expand on a relatively new proposal for why these and other populations may not show major signs of these diseases. Chronic infections, especially helminths, may offer protection against heart disease and diabetes through direct and indirect pathways. As part of a strategy to insure their own survival and reproduction, helminths exert multiple cardio-protective effects on their host through their effects on immune function and blood lipid metabolism. Helminths consume blood lipids and glucose, alter lipid metabolism, and modulate immune function towards Th-2 polarization—which combined can lower blood cholesterol, reduce obesity, increase insulin sensitivity, decrease atheroma progression, and reduce likelihood of atherosclerotic plaque rupture. Traditional cardiometabolic risk factors, coupled with the mismatch between our evolved immune systems and modern, hygienic environments may interact in complex ways. In this review, we survey existing studies in the non-human animal and human literature, highlight unresolved questions and suggest future directions to explore the role of helminths in the etiology of cardio-metabolic disease

Methodological Differences Cannot Explain Associations Between Health, Anthropometrics, and Excess Resting Metabolic Rate

We appreciate Ocobock\u27s interest in methodological rigor. We largely agree with her commentary, which suggests that departures from standard protocols might have contributed to the high resting metabolic rate (RMR) measured for Tsimane. Indeed, our paper acknowledges many of the key departures from gold-standard indirect calorimetry methods of RMR assessment and attempts to adjust for several of these (Gurven et al., 2016). Bringing standard clinical methods into remote field settings often involves certain compromises, especially in our case, where RMR measurement was just one component of a large-scale health and aging project (Gurven et al., 2017). RMR data collection was from 2012 to 2014, and where we to measure RMR again for focused follow up, we would consider new available technologies, improve our protocol to the extent possible, and compare against our published estimates

Associations Between Male Testosterone and Immune Function in a Pathogenically Stressed Forager-Horticultural Population

Objectives—Despite well-known fitness advantages to males who produce and maintain high endogenous testosterone levels, such phenotypes may be costly if testosterone-mediated investment in reproductive effort trade-off against investment in somatic maintenance. Previous studies of androgen-mediated trade-offs in human immune function find mixed results, in part because most studies either focus on a few indicators of immunity, are confounded by phenotypic correlation, or are observational. Here the association between male endogenous testosterone and 13 circulating cytokines are examined before and after ex vivo antigen stimulation with phytohaemagglutinin (PHA) and lipopolysaccharides (LPS) in a high pathogen population of Bolivian forager-horticulturalists. Materials and Methods—A Milliplex 13-plex cytokine panel measured cytokine concentration in whole blood samples from 109 Tsimane men aged 40–89 (median=50 years) before and after antigen stimulation with PHA and LPS. Urinary testosterone was measured via enzyme immunoassay; demographic and anthropometric data were collected as part of the Tsimane Health and Life History Project. Results—Higher endogenous testosterone was associated with down-regulated responses in all cytokines after PHA stimulation (but significantly in only 2/13 cytokines), controlling for age and body mass index. In contrast, testosterone was not significantly associated with down-regulation of cytokines after LPS stimulation. MANOVAs indicate that men with higher testosterone showed reduced cytokine responses to PHA compared to LPS (p=0.0098). Discussion—Endogenous testosterone appears to be immunomodulatory rather than immunosuppressive. Potentially costlier forms of immune activation like those induced by PHA (largely T-cell biased immune activation) are down-regulated in men with higher testosterone, but testosterone has less impact on potentially less costly immune activation following LPS stimulation (largely B-cell mediated immunity)

The Tsimane Health and Life History Project: Integrating Anthropology and Biomedicine

The Tsimane Health and Life History Project, an integrated bio-behavioral study of the human life course, is designed to test competing hypotheses of human life-history evolution. One aim is to understand the bidirectional connections between life history and social behavior in a highfertility, kin-based context lacking amenities of modern urban life (e.g. sanitation, banks, electricity). Another aim is to understand how a high pathogen burden influences health and well-being during development and adulthood. A third aim addresses how modernization shapes human life histories and sociality. Here we outline the project’s goals, history, and main findings since its inception in 2002. We reflect on the implications of current findings and highlight the need for more coordinated ethnographic and biomedical study of contemporary nonindustrial populations to address broad questions that can situate evolutionary anthropology in a key position within the social and life sciences

Helminth Infection, Fecundity, and Age of First Pregnancy in Women

Infection with intestinal helminths results in immunological changes that influence the odds of comorbid infections, and might also affect fecundity by inducing immunological states supportive of conception and pregnancy. Here we investigate associations between intestinal helminths and fertility in human females, utilizing nine years of longitudinal data from 986 Bolivian forger-horticulturalists, experiencing natural fertility and a 70% helminth prevalence. We find that different species of helminth are associated with opposing effects on fecundity. Infection with roundworm (Ascaris lumbricoides) is associated with earlier first births and shortened interbirth intervals, while infection with hookworm is associated with delayed first pregnancy and extended interbirth intervals. Thus, helminths may have important, and sometimes contradictory effects on human fertility, reflecting the physiological and immunological consequences of infection with particular species

Political Influence Associates With Cortisol and Health Among Egalitarian Forager-Farmers

Background and objectives: Low social status increases risk of disease due, in part, to the psychosocial stress that accompanies feeling subordinate or poor. Previous studies report that chronic stress and chronically elevated cortisol can impair cardiovascular and immune function. We test whether lower status is more benign in small-scale, relatively egalitarian societies, where leaders lack coercive authority and there is minimal material wealth to contest. Methodology: Among Tsimane’ forager-horticulturalists of lowland Bolivia, we compare informal political influence among men with urinary cortisol, immune activation (innate and acquired), and morbidity as assessed during routine medical exams. Results: After controlling for potential confounds, we find that politically influential men have lower cortisol, and that this association is partly attributable to access to social support. Cortisol is positively associated with men’s income, which may reflect chronic psychosocial stress from market involvement. Greater influence is also associated with lower probability of respiratory infection, which is a frequent source of morbidity among Tsimane’. Among men who lost influence over a 4-year period, cortisol and probability of respiratory infection were higher the greater the decline in influence. Conclusions and implications: Deleterious effects of low status on health are not merely ‘diseases of civilization’ but may result from how (even subtle) status differences structure human behavior

Growth References for Tsimane Forager-Horticulturalists of the Bolivian Amazon

Objectives—Growth standards and references currently used to assess population and individual health are derived primarily from urban populations, including few individuals from indigenous or subsistence groups. Given environmental and genetic differences, growth may vary in these populations. Thus, there is a need to assess whether international standards are appropriate for all populations, and to produce population specific references if growth differs. Here we present and assess growth references for the Tsimane, an indigenous population of Bolivian forager-horticulturalists. Methods—Mixed cross-sectional/longitudinal anthropometrics (9,614 individuals; 30,118 observations; ages 0–29 years) were used to generate centile curves and Lambda-Mu-Sigma (LMS) tables for height-for-age, weight-for-age, body mass index (BMI)-for-age, and weight-for-height (WFH) using Generalized Additive Models for Location Shape and Scale (GAMLSS). Velocity curves were generated using SuperImposition by Translation and Rotation (SITAR). Tsimane ≤5 years were compared World Health Organization (WHO) standards while those \u3e5 years were compared to WHO school age references. All ages were compared to published references for Shuar forager-horticulturalists of the Ecuadorian Amazon. Results—Tsimane growth differs from WHO values in height and weight, but is similar for BMI and WFH. Tsimane growth is characterized by slow height velocity in childhood and early adolescent peak height velocity at 11.3 and 13.2 years for girls and boys. Tsimane growth patterns are similar to Shuar, suggesting shared features of growth among indigenous South Americans. Conclusions—International references for BMI-for-age and WFH are likely appropriate for Tsimane, but differences in height-for-age and weight-for-age suggest Tsimane specific references may be useful for these measures