Humans have the longest post-reproductive lifespans and lowest rates of actuarial ageing among primates. Understanding the links between slow actuarial ageing and physiological change is critical for improving the human 'healthspan'. Physiological dysregulation may be a key feature of ageing in industrialized populations with high burdens of chronic 'diseases of civilization', but little is known about age trajectories of physiological condition in subsistence populations with limited access to public health infrastructure. To better characterize human physiological dysregulation, we examined age trajectories of 40 biomarkers spanning the immune (n = 13 biomarkers), cardiometabolic (n = 14), musculoskeletal (n = 6) and other (n = 7) systems among Tsimane forager-horticulturalists of the Bolivian Amazon using mixed cross-sectional and longitudinal data (n = 22 115 observations). We characterized age-related changes using a multi-system statistical index of physiological dysregulation (Mahalanobis distance; D_m) that increases with age in both humans and other primates. Although individual biomarkers showed varied age profiles, we found a robust increase in age-related dysregulation for Tsimane (β = 0.17-0.18) that was marginally faster than that reported for an industrialized Western sample (β = 0.14-0.16), but slower than that of other non-human primates. We found minimal sex differences in the pace or average level of dysregulation for Tsimane. Our findings highlight some conserved patterns of physiological dysregulation in humans, consistent with the notion that somatic ageing exhibits species-typical patterns, despite cross-cultural variation in environmental exposures, lifestyles and mortality. This article is part of the theme issue 'Evolution of the primate ageing process'.

Controversy over the adaptive significance of male hunting in subsistence societies hinges on the relative importance of familial provisioning and mate-quality signalling. This paper examines the proximate and ultimate motivations of hunting behaviour from a neuroendocrine perspective, using salivary testosterone and cortisol data collected before, during and after hunting focal follows from 31 Tsimane hunters aged 18-82 years. Despite circadian declines in hormone levels, testosterone and cortisol of Tsimane hunters increased at the time of a kill, and remained high as successful hunters returned home. Previous studies of hormonal changes during competitions find that high-stakes and success in the presence of relevant audiences result in increased neuroendocrine arousal. If men hunt primarily to provision their families, then an additional audience would not be expected to impact testosterone or cortisol, nor would the size of the animal killed. However, if signalling male quality by 'showing off' was a larger relative driver of men's hunting behaviour, one would expect greater hormonal response in cases where men returned with large sharable kills, especially in the presence of community members. Consistent with provisioning models of male hunting motivation, neither kill size nor encountering an audience of villagers while returning from hunting was associated with hormonal changes for successful hunters.

Background

In an energy-limited environment, caloric investments in one characteristic should trade-off with investments in other characteristics. In high pathogen ecologies, biasing energy allocation towards immune function over growth would be predicted, given strong selective pressures against early-life mortality.

Methodology

In the present study, we use flow cytometry to examine trade-offs between adaptive immune function (T cell subsets, B cells), innate immune function (natural killer cells), adaptive to innate ratio and height-for-age z scores (HAZ) among young children (N = 344; aged 2 months-8 years) in the Bolivian Amazon, using maternal BMI and child weight-for-height z scores (WHZ) as proxies for energetic status.

Results

Markers of adaptive immune function negatively associate with child HAZ, a pattern most significant in preadolescents (3+ years). In children under three, maternal BMI appears to buffer immune and HAZ associations, while child energetic status (WHZ) moderates relationships in an unexpected direction: HAZ and immune associations are greater in preadolescents with higher WHZ. Children with low WHZ maintain similar levels of adaptive immune function, but are shorter compared to high WHZ peers.

Conclusions

Reduced investment in growth in favor of immunity may be necessary for survival in high pathogen contexts, even under energetic constraints. Further, genetic and environmental factors are important considerations for understanding variation in height within this population. These findings prompt consideration of whether there may be a threshold of investment into adaptive immunity required for survival in high pathogen environments, and thus question the universal relevance of height as a marker of health.

Lay summary

Adaptive immune function is negatively associated with child height in this high pathogen environment. Further, low weight-for-height children are shorter but maintain similar immune levels. Findings question the relevance of height as a universal health marker, given that costs and benefits of height versus immunity may be calibrated to local ecology.

In comparative cross-species perspective, humans experience unique physical impairments with potentially large consequences. Quantifying the burden of impairment in subsistence populations is critical for understanding selection pressures underlying strategies that minimize risk of production deficits. We examine among forager-horticulturalists whether compromised bone strength (indicated by fracture and lower bone mineral density, BMD) is associated with subsistence task cessation. We also estimate the magnitude of productivity losses associated with compromised bone strength. Fracture is associated with cessation of hunting, tree chopping, and walking long distances, but not tool manufacture. Age-specific productivity losses from hunting cessation associated with fracture and lower BMD are substantial: ~397 lost kcals/day, with expected future losses of up to 1.9 million kcals (22% of expected production). Productivity loss is thus substantial for high strength and endurance tasks. Determining the extent to which impairment obstructs productivity in contemporary subsistence populations improves our ability to infer past consequences of impairment.

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 forager-horticulturalists, 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.

Background

Traditional diets are often credited for the robust cardiometabolic health of subsistence populations. Yet, rural subsistence populations are undergoing nutrition transitions that have been linked to the increase in chronic noncommunicable diseases. Few studies have presented detailed dietary estimates in transitioning populations.

Objectives

We aimed to 1) characterize and compare dietary profiles of 2 neighboring subsistence populations in Bolivia who vary in market integration and 2) identify dietary factors contributing to low cardiovascular disease risk.

Design

We used a mixed longitudinal design to estimate nutrient intake via 24-h recall and dietary questionnaires among 1299 Tsimane (aged 30-91 y) and 229 Moseten (aged 30-84 y) men and women. We constructed population-level estimates of energy intake, dietary diversity, and nutrient shortfalls and analyzed dietary changes over time and space using multilevel models. Last, we compared Tsimane and Moseten dietary profiles with those of Americans (NHANES).

Results

The Tsimane diet was characterized by high energy (2422-2736 kcal/d), carbohydrate (376-423 g/d), and protein (119-139 g/d) intakes; low fat intake (40-46 g/d); and low dietary diversity relative to the average US diet. Most calories (64%) were derived from complex carbohydrates. Total energy and carbohydrate intake increased significantly during the 5-y study, particularly in villages near market towns. Tsimane consumption of food additives (lard, oil, sugar, salt) increased significantly [sugar (15.8 g ⋅ person-1 ⋅ d-1) and oil (4.9 mL ⋅ person-1 ⋅ d-1)] between 2010 and 2015. The more-acculturated Moseten consumed substantially more sugar (by 343%) and oil (by 535%) than the Tsimane.

Conclusions

A high-energy diet rich in complex carbohydrates is associated with low cardiovascular disease risk when coupled with a physically active lifestyle. A transition away from a high-fiber and low-fat, low-salt, and low-processed-sugar diet is a salient health risk for transitioning populations. Evidence of a nutrition transition in Bolivia parallels trends of increasing body fat and body mass index, which suggests that a low prevalence of cardiovascular disease may not persist.

Background

Amazonian populations are exposed to diverse parasites and pathogens, including protozoal, bacterial, fungal and helminthic infections. Yet much knowledge of the immune system is based on industrialised populations where these infections are relatively rare.

Aim

This study examines distributions and age-related differences in 22 measures of immune function for Bolivian forager-horticulturalists and US and European populations.

Subjects and methods

Subjects were 6338 Tsimane aged 0-90 years. Blood samples collected between 2004-2014 were analysed for 5-part blood differentials, C-reactive protein, erythrocyte sedimentation rate (ESR) and total immunoglobulins E, G, A and M. Flow cytometry was used to quantify naïve and non-naïve CD4 and CD8 T cells, natural killer cells, and B cells.

Results

Compared to reference populations, Tsimane have elevated levels of most immunological parameters, particularly immunoglobulins, eosinophils, ESR, B cells, and natural killer cells. However, monocytes and basophils are reduced and naïve CD4 cells depleted in older age groups.

Conclusion

Tsimane ecology leads to lymphocyte repertoires and immunoglobulin profiles that differ from those observed in industrialised populations. These differences have consequences for disease susceptibility and co-vary with patterns of other life history traits, such as growth and reproduction.

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 phytohemagglutinin (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 with 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).

Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistence-level 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.

Background

Often considered an inevitable part of male aging, benign prostatic hyperplasia (BPH) is the most common non-life threatening disease to affect men in Western populations. We examine age-related change in prostate size and BPH risk and related serum biomarkers among the Tsimane Amerindians of the Bolivian Amazon who live a traditional lifestyle of hunting and small-scale horticulture. The Tsimane are a critical case study for understanding the etiology of BPH as they have low levels of obesity and metabolic syndrome, as well as lower levels of testosterone than age matched U.S. males, factors associated with BPH in previous research.

Methods

Ultrasounds were conducted on 348 men aged 28-89 years (median age 56 years). Testosterone, prostate specific antigen, sex hormone binding globulin, and glycosylated hemoglobin were examined in relationship to prostate size and BPH.

Results

Tsimane have less than half of the BPH prevalence experienced by U.S. men, and prostate volumes 62.6% smaller. While Tsimane have low levels of testosterone and subclinical levels of metabolic syndrome compared to U.S. men, Tsimane with high testosterone were more likely to experience BPH, as were those with higher glycosylated hemoglobin, suggesting targets for clinical interventions to reduce BPH.

Conclusions

These results have clinical significance for the growing number of men taking testosterone supplementation; even at low levels the additional testosterone exposure could be placing these men at higher risk of BPH. Overall, these data suggest that BPH may not have been an inevitable part of male aging throughout human evolutionary history.