Poor oral health is associated with inflammation, aortic valve calcification, and brain volume among forager-farmers.

Poor oral health is associated with cardiovascular disease and dementia. Potential pathways include sepsis from oral bacteria, systemic inflammation, and nutritional deficiencies. However, in post-industrialized populations, links between oral health and chronic disease may be confounded because the lower socioeconomic exposome (poor diet, pollution, low physical activity) often entails insufficient dental care. We assessed tooth loss, caries, and damaged teeth, in relation to cardiovascular and brain aging among the Tsimane, a subsistence population living a relatively traditional forager-horticulturalist lifestyle with poor dental health, but minimal cardiovascular disease and dementia. Dental health was assessed by a physician in 739 participants aged 40-92 years with cardiac and brain health measured by chest computed tomography (CT) (n=728) and brain CT (n=605). A subset of 356 individuals aged 60+ were also assessed for dementia and mild cognitive impairment (n=33 impaired). Tooth loss was highly prevalent, with 2.2 teeth lost per decade and a 2-fold greater loss in women. The number of teeth with exposed pulp was associated with higher inflammation, as measured by cytokine levels and white blood cell counts, and lower body mass index. Coronary artery calcium and thoracic aortic calcium were not associated with tooth loss or damaged teeth. However, aortic valve calcification and brain tissue loss were higher in those that had more teeth with exposed pulp. Overall, these results suggest that dental health is associated with indicators of chronic diseases in the absence of typical confounds, even in a population with low cardiovascular and dementia risk factors.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

Background: In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. Methodology: In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). Results: Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007). Conclusions and Implications: Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.

Adolescence is characterized by more sedentary behaviour and less physical activity even among highly active forager-farmers.

Over 80% of adolescents worldwide are insufficiently active, posing massive public health and economic challenges. Declining physical activity (PA) and sex differences in PA consistently accompany transitions from childhood to adulthood in post-industrialized populations and are attributed to psychosocial and environmental factors. An overarching evolutionary theoretical framework and data from pre-industrialized populations are lacking. This cross-sectional study tests hypotheses from life history theory, that adolescent PA is inversely related to age, but this association is mediated by Tanner stage, reflecting higher and sex-specific energetic demands for growth and reproductive maturation. Detailed measures of PA and pubertal maturation are assessed among Tsimane forager-farmers (age: 7-22 years; 50% female, n = 110). Most Tsimane sampled (71%) meet World Health Organization PA guidelines (greater than or equal to 60 min/day of moderate-to-vigorous PA). Like post-industrialized populations, sex differences and inverse age-activity associations were observed. Tanner stage significantly mediated age-activity associations. Adolescence presents difficulties to PA engagement that warrant further consideration in PA intervention approaches to improve public health.

Applying an evolutionary mismatch framework to understand disease susceptibility.

Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.

Metapopulation dynamics of SARS-CoV-2 transmission in a small-scale Amazonian society.

The severity of infectious disease outbreaks is governed by patterns of human contact, which vary by geography, social organization, mobility, access to technology and healthcare, economic development, and culture. Whereas globalized societies and urban centers exhibit characteristics that can heighten vulnerability to pandemics, small-scale subsistence societies occupying remote, rural areas may be buffered. Accordingly, voluntary collective isolation has been proposed as one strategy to mitigate the impacts of COVID-19 and other pandemics on small-scale Indigenous populations with minimal access to healthcare infrastructure. To assess the vulnerability of such populations and the viability of interventions such as voluntary collective isolation, we simulate and analyze the dynamics of SARS-CoV-2 infection among Amazonian forager-horticulturalists in Bolivia using a stochastic network metapopulation model parameterized with high-resolution empirical data on population structure, mobility, and contact networks. Our model suggests that relative isolation offers little protection at the population level (expected approximately 80% cumulative incidence), and more remote communities are not conferred protection via greater distance from outside sources of infection, due to common features of small-scale societies that promote rapid disease transmission such as high rates of travel and dense social networks. Neighborhood density, central household location in villages, and household size greatly increase the individual risk of infection. Simulated interventions further demonstrate that without implausibly high levels of centralized control, collective isolation is unlikely to be effective, especially if it is difficult to restrict visitation between communities as well as travel to outside areas. Finally, comparison of model results to empirical COVID-19 outcomes measured via seroassay suggest that our theoretical model is successful at predicting outbreak severity at both the population and community levels. Taken together, these findings suggest that the social organization and relative isolation from urban centers of many rural Indigenous communities offer little protection from pandemics and that standard control measures, including vaccination, are required to counteract effects of tight-knit social structures characteristic of small-scale populations.

Apolipoprotein-ε4 is associated with higher fecundity in a natural fertility population.

In many populations, the apolipoprotein-ε4 (APOE-ε4) allele increases the risk for several chronic diseases of aging, including dementia and cardiovascular disease; despite these harmful effects at later ages, the APOE-ε4 allele remains prevalent. We assess the impact of APOE-ε4 on fertility and its proximate determinants (age at first reproduction, interbirth interval) among the Tsimane, a natural fertility population of forager-horticulturalists. Among 795 women aged 13 to 90 (20% APOE-ε4 carriers), those with at least one APOE-ε4 allele had 0.3 to 0.5 more children than (ε3/ε3) homozygotes, while those with two APOE-ε4 alleles gave birth to 1.4 to 2.1 more children. APOE-ε4 carriers achieve higher fertility by beginning reproduction 0.8 years earlier and having a 0.23-year shorter interbirth interval. Our findings add to a growing body of literature suggesting a need for studies of populations living in ancestrally relevant environments to assess how alleles that are deleterious in sedentary urban environments may have been maintained by selection throughout human evolutionary history.

Energetic costs of testosterone in two subsistence populations.

OBJECTIVE: Testosterone plays a role in mediating energetic trade-offs between growth, maintenance, and reproduction. Investments in a high testosterone phenotype trade-off against other functions, particularly survival-enhancing immune function and cellular repair; thus only individuals in good condition can maintain both a high testosterone phenotype and somatic maintenance. While these effects are observed in experimental manipulations, they are difficult to demonstrate in free-living animals, particularly in humans. We hypothesize that individuals with higher testosterone will have higher energetic expenditures than those with lower testosterone. METHODS: Total energetic expenditure (TEE) was quantified using doubly labeled water in n = 40 Tsimane forager-horticulturalists (50% male, 18-87 years) and n = 11 Hadza hunter-gatherers (100% male, 18-65 years), two populations living subsistence lifestyles, high levels of physical activity, and high infectious burden. Urinary testosterone, TEE, body composition, and physical activity were measured to assess potential physical and behavioral costs associated with a high testosterone phenotype. RESULTS: Endogenous male testosterone was significantly associated with energetic expenditure, controlling for fat free mass; a one standard deviation increase in testosterone is associated with the expenditure of an additional 96-240 calories per day. DISCUSSION: These results suggest that a high testosterone phenotype, while beneficial for male reproduction, is also energetically expensive and likely only possible to maintain in healthy males in robust condition.

Labour's pain: strenuous subsistence work, mechanical wear-and-tear and musculoskeletal pain in a non-industrialized population.

Musculoskeletal pain is the most debilitating human health condition. Neurophysiological pain mechanisms are highly conserved and promote somatic maintenance and learning to avoid future harm. However, some chronic pain might be more common owing to mismatches between modern lifestyles and traits that originally evolved under distinct premodern conditions. To inform assumptions about factors affecting chronic pain vulnerability prior to industrialization, we assess pain prevalence, perceived causes, and predictors among Tsimane forager-horticulturalists. Habitual subsistence work is the primary reported cause of pain throughout life for both sexes, and pain is more common with age, especially in the back, and for those with more musculoskeletal problems. Sex differences in pain are relatively weak, and we find no association between women's reproductive history and pain, contrary to the hypothesis that reproduction causes women's greater pain susceptibility. Age-standardized current pain prevalence is 1.7-8.2 times higher for Tsimane than other select populations, and Tsimane chronic pain prevalence is within the range of variation observed elsewhere. Chronic low back pain is not a 'mismatch disease' limited to post-industrialized populations. Hominin musculoskeletal changes supporting bipedalism probably imposed health costs, which, after millions of years of evolution, remain an epidemiological burden that may be exacerbated by modern conditions.

Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.

Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.

Adolescence is characterized by more sedentary behavior and less physical activity even among highly active forager-farmers.

Over 80% of adolescents worldwide are insufficiently active, posing massive public health and economic challenges. Declining physical activity (PA) and sex differences in PA consistently accompany transitions from childhood to adulthood in post-industrialized populations and are attributed to psychosocial and environmental factors. An overarching evolutionary theoretical framework and data from pre-industrialized populations are lacking. In this cross-sectional study we test a hypothesis from life history theory, that adolescent PA reductions reflect an evolved strategy to conserve energy, given the increasing sex-specific energetic demands for growth and reproductive maturation. Detailed measures of PA and pubertal maturation are assessed among Tsimane forager-farmers (age: 7-22 yrs.; 50% female, n=110). We find that 71% of Tsimane sampled meet World Health Organization PA guidelines (≥60 minutes/day of moderate-to-vigorous PA). Consistent with post-industrialized populations, we observe sex differences and inverse age-activity associations mediated by Tanner stage. Physical inactivity in adolescence is distinct from other health risk behaviors and also not merely resulting from obesogenic environments.

Evolutionary mismatch and the role of GxE interactions in human disease.

Globally, we are witnessing the rise of complex, non-communicable diseases (NCDs) related to changes in our daily environments. Obesity, asthma, cardiovascular disease, and type 2 diabetes are part of a long list of "lifestyle" diseases that were rare throughout human history but are now common. A key idea from anthropology and evolutionary biology-the evolutionary mismatch hypothesis-seeks to explain this phenomenon. It posits that humans evolved in environments that radically differ from the ones experienced by most people today, and thus traits that were advantageous in past environments may now be "mismatched" and disease-causing. This hypothesis is, at its core, a genetic one: it predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions and have differential health effects in ancestral versus modern environments. Here, we discuss how this concept could be leveraged to uncover the genetic architecture of NCDs in a principled way. Specifically, we advocate for partnering with small-scale, subsistence-level groups that are currently transitioning from environments that are arguably more "matched" with their recent evolutionary history to those that are more "mismatched". These populations provide diverse genetic backgrounds as well as the needed levels and types of environmental variation necessary for mapping GxE interactions in an explicit mismatch framework. Such work would make important contributions to our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and sociocultural contexts.

Prevalence of dementia and mild cognitive impairment in indigenous Bolivian forager-horticulturalists.

INTRODUCTION: We evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle. METHODS: Participants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans. RESULTS: Tsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia. DISCUSSION: The prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

Female cooperative labour networks in hunter-gatherers and horticulturalists.

Cooperation in food acquisition is a hallmark of the human species. Given that costs and benefits of cooperation vary among production regimes and work activities, the transition from hunting-and-gathering to agriculture is likely to have reshaped the structure of cooperative subsistence networks. Hunter-gatherers often forage in groups and are generally more interdependent and experience higher short-term food acquisition risk than horticulturalists, suggesting that cooperative labour should be more widespread and frequent for hunter-gatherers. Here we compare female cooperative labour networks of Batek hunter-gatherers of Peninsular Malaysia and Tsimane forager-horticulturalists of Bolivia. We find that Batek foraging results in high daily variation in labour partnerships, facilitating frequent cooperation in diffuse networks comprised of kin and non-kin. By contrast, Tsimane horticulture involves more restricted giving and receiving of labour, confined mostly to spouses and primary or distant kin. Tsimane women also interact with few individuals in the context of hunting/fishing activities and forage mainly with spouses and primary kin. These differences give rise to camp- or village-level networks that are more modular (have more substructure when partitioned) among Tsimane horticulturalists. Our findings suggest that subsistence activities shape the formation and extent of female social networks, particularly with respect to connections with other women and non-kin. We discuss the implications of restricted female labour networks in the context of gender relations, power dynamics and the adoption of farming in humans. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.

Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations.

A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype-phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4, MUC21 and MUC22, TOX2, ANXA6, and ABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.

There and back again: The biosocial dynamics of returning from the field.

BACKGROUND: Leaving "home" to pursue fieldwork is a necessity but also a rite of passage for many biological anthropology/human biology scholars. Field-based scientists prepare for the potential changes to activity patterns, sleep schedules, social interactions, and more that come with going to the field. However, returning from extended fieldwork and the reverse-culture shock, discomforts, and mental shifts that are part of the return process can be jarring, sometimes traumatic experiences. A failure to acknowledge and address such experiences can compromise the health and wellbeing of those returning. AIMS: We argue for an engaged awareness of the difficult nature of returning from the field and offer suggestions for individuals and programs to better train and prepare PhD students pursuing fieldwork. MATERIALS & METHODS: Here, we offer personal stories of "coming back" and give professional insights on how to best ready students and scholars for returning from fieldwork. DISCUSSION/CONCLUSION: By bringing forward and normalizing the difficulty of the fieldwork-return process, we hope that this reflection acts as a tool for future scholars to prepare to come home as successfully and consciously as possible.

Helminth infection is associated with dampened cytokine responses to viral and bacterial stimulations in Tsimane forager-horticulturalists.

BACKGROUND: Soil-transmitted helminths (STHs) and humans share long co-evolutionary histories over which STHs have evolved strategies to permit their persistence by downregulating host immunity. Understanding the interactions between STHs and other pathogens can inform our understanding of human evolution and contemporary disease patterns. METHODOLOGY: We worked with Tsimane forager-horticulturalists in the Bolivian Amazon, where STHs are prevalent. We tested whether STHs and eosinophil levels-likely indicative of infection in this population-are associated with dampened immune responses to in vitro stimulation with H1N1 and lipopolysaccharide (LPS) antigens. Whole blood samples (n = 179) were treated with H1N1 vaccine and LPS and assayed for 13 cytokines (INF-γ, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, GM-CSF and TNF-ɑ). We evaluated how STHs and eosinophil levels affected cytokine responses and T helper (Th) 1 and Th2-cytokine suite responses to stimulation. RESULTS: Infection with Ascaris lumbricoides was significantly (P ≤ 0.05) associated with lower response of some cytokines to H1N1 and LPS in women. Eosinophils were significantly negatively associated with some cytokine responses to H1N1 and LPS, with the strongest effects in women, and associated with a reduced Th1- and Th2-cytokine response to H1N1 and LPS in women and men. CONCLUSIONS AND IMPLICATIONS: Consistent with the 'old friends' and hygiene hypotheses, we find that STHs were associated with dampened cytokine responses to certain viral and bacterial antigens. This suggests that STH infections may play an essential role in immune response regulation and that the lack of STH immune priming in industrialized populations may increase the risk of over-reactive immunity. Lay Summary: Indicators of helminth infection were associated with dampened cytokine immune responses to in vitro stimulation with viral and bacterial antigens in Tsimane forager-horticulturalists in the Bolivian Amazon, consistent with the 'old friends' and hygiene hypotheses.

APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population.

In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N = 1266, 50% female), APOE4 is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.

Genes contain the instructions needed for a cell to make molecules called proteins, which perform various roles in the body. Different variants of a gene can affect how the protein works, and in some cases, can increase a person's risk to develop certain diseases. For example, people who carry a version of the apolipoprotein E gene called APOE4 have a greater risk of developing Alzheimer's disease or heart disease. Individuals with two copies of this genetic variant have a 45% higher risk of heart disease and 12 times higher risk of Alzheimer's disease. Studies in industrialized countries suggest this increased risk may be the result of higher cholesterol and inflammation in people with APOE4. But if APOE4 is harmful, why does it continue to be so common worldwide? One potential explanation is that APOE4, which has been around since before modern humans, may be beneficial in some contexts. Cholesterol is essential for many vital tasks in the body. In physically demanding environments where parasitic infections are common ­ conditions similar to those experienced by early humans ­ APOE4 might be beneficial. Under those circumstances, having more cholesterol might help fuel metabolic activities, fight infections, or reduce inflammation caused by infections. Garcia et al. investigated the link between the APOE4 genetic variant, cholesterol and inflammation in 1,266 Indigenous Tsimane people from 80 villages in Bolivia. Tsimane people live an active lifestyle foraging and farming for food. Parasite infections are a common problem in their communities, but obesity rates are very low. Garcia et al. found that Tsimane people with at least one copy of the APOE4 have lower levels of inflammation and higher levels of cholesterol than those who have two copies of the APOE3 version of the gene. Very lean people with APOE4 had especially high levels of the so called "bad" low density lipoprotein (LDL) cholesterol compared to people with APOE3 only. However, in this situation, storing a little extra cholesterol may not be so bad. The findings contradict other studies that have linked obesity to higher LDL levels and APOE4 to higher levels of inflammation. For the majority of human history, humans lived in more physically strenuous and calorically restrictive environments, with less access to clean water. Garcia et al. suggest that the harmful effects of APOE4 seen in studies in more industrialized societies ­ where people tend to be more sedentary and have less exposure to pathogens ­ may reflect a mismatch between a person's environment and their genes. More studies that capture the diversity of environmental conditions under which people live will help clarify the role of APOE4 health and disease.

High prevalence of sternal foramina in indigenous Bolivians compared to Midwest Americans and indigenous North Americans (sternal foramina in indigenous Bolivians).

The sternal foramen, usually an asymptomatic osteological defect, can lead to catastrophic consequences if not recognized prior to certain medical procedures. This study reports the prevalence of a sternal foramen in two South Amerindian populations compared with other published populations. We evaluated the presence of sternal foramina using thoracic computed tomography scans of 1334 (48% female) participants from two indigenous populations of Bolivia (n = 900 Tsimane, 434 Moseten). The prevalence of sternal foramina was compared to two U.S. populations of similar sex/age distribution (n = 572 Midwest Americans, 131 self-identified Native North Americans) via similar CT scans. A sternal foramen was significantly more common in the two Bolivian populations (prevalence ranging from 12.8 to 13.4%), compared to 4.4-5.1% in the two U.S. groups, consistent with prior estimates in studies from industrialized populations. Males had higher frequency of a sternal foramen compared to females in each of the four groups (OR = 1.904, 95% CI: 1.418-2.568, p < 0.001). Age was not associated with sternal foramen presence. These data show both a higher rate of sternal foramina in the South Amerindian populations versus comparator populations in North America and the highest rate of any studied living population. Although it is not possible to determine from our data the relative contribution of genetics versus early life or environmental causes to the higher rates of sternal foramen, we note that small prior studies have likewise demonstrated a higher prevalence in lower income countries. Further determination of the contributing factors warrants greater investigation and research.

Do wealth and inequality associate with health in a small-scale subsistence society?

In high-income countries, one's relative socio-economic position and economic inequality may affect health and well-being, arguably via psychosocial stress. We tested this in a small-scale subsistence society, the Tsimane, by associating relative household wealth (n = 871) and community-level wealth inequality (n = 40, Gini = 0.15-0.53) with a range of psychological variables, stressors, and health outcomes (depressive symptoms [n = 670], social conflicts [n = 401], non-social problems [n = 398], social support [n = 399], cortisol [n = 811], body mass index [n = 9,926], blood pressure [n = 3,195], self-rated health [n = 2523], morbidities [n = 1542]) controlling for community-average wealth, age, sex, household size, community size, and distance to markets. Wealthier people largely had better outcomes while inequality associated with more respiratory disease, a leading cause of mortality. Greater inequality and lower wealth were associated with higher blood pressure. Psychosocial factors did not mediate wealth-health associations. Thus, relative socio-economic position and inequality may affect health across diverse societies, though this is likely exacerbated in high-income countries.

Poverty is bad for health. People living in poverty are more likely to struggle to afford nutritious food, lack access to health care, or be overworked or stressed. This may make them susceptible to chronic diseases, contribute to faster aging, and shorten their lifespans. In high-income countries, there is growing evidence to suggest that a person's 'rank' in society also impacts their health. For example, individuals who have a lower position in the social hierarchy report worse health outcomes, regardless of their incomes. But it is unclear why living in an unequal society or having a lower social status contributes to poorer health. One possibility is that inequalities in society are creating a stressful environment that leads to worse physical and mental outcomes. It is thought that this stress largely comes from how humans evolved to prioritize reaching a higher social status over having a long and healthy life. If this is the case, this would mean that the link between social status and health would also be present in non-industrialized communities where social hierarchies tend to be less pronounced. To test this, Jaeggi, Blackwell et al. studied the Indigenous Tsimane population in Bolivia who live in small communities and forage and farm their own food. The income and relative wealth of 870 households from 40 Tsimane communities were compared against various outcomes, including symptoms associated with depression, stress hormone levels, blood pressure, self-rated health and several diseases. Jaeggi, Blackwell et al. found poverty and inequality did not negatively impact all of the health outcomes measured as has been previously reported for industrialized societies. However, blood pressure was higher among people with lower incomes or those who lived in more unequal communities. But because the Tsimane people generally have low blood pressure, the differences were too small to have much effect on their health. People who lived in more unequal communities were also three times more likely to have respiratory infections, but the reason for this was unclear. This shows that social determinants such as a person's wealth or inequality can affect health, even in communities with less rigid social hierarchies. In industrial societies the effect may be worse in part because they are compounded by lifestyle factors, such as diets rich in fat and sugar, and physical inactivity which can also increase blood pressure. This information may help policy makers reduce health disparities by addressing some of the social determinants of health and the lifestyle factors that cause them.

The Indigenous South American Tsimane Exhibit Relatively Modest Decrease in Brain Volume With Age Despite High Systemic Inflammation.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40-94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate ß^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. ß^T was compared to the corresponding regression coefficient estimate ß^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis ß T = ß R was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.