Background:The early-life environment has a significant influence on health in later life, including the risk of cardiometabolic diseases (CMDs). Several biomarkers have been proposed as putative indicators of early-life environmental quality, including facial fluctuating asymmetry (FA) and facial averageness (AVE). This study aimed to explore the association between facial FA and AVE with CMDs risk factors in women of post-reproductive age. Methods:The participants were 248 post-reproductive women (M = 61.6, SD = 10.70) from the Mogielica Human Ecology Study Site in Poland. Standardized facial photographs were taken, and FA and AVE were calculated using geometric morphometrics. Fasting blood samples were collected, and blood pressure was measured directly. Body composition was assessed via bioelectrical impedance analysis. CMDs risk factors included blood pressure, total cholesterol, high-density and low-density lipoproteins, triglycerides, and glucose levels. Additionally, the risk of metabolic syndrome was determined for each participant. Cardiovascular disease risk was also evaluated using the Systematic Coronary Risk Estimation scale (SCORE). FA and AVE were modelled separately against each CMDs risk factor using hierarchical linear and logistic models. Results:No statistically significant associations were found between either FA or AVE and individual CMDs risk factors. Similarly, no relationships were observed between facial measurements and either SCORE or metabolic syndrome risk. Follow-up Bayesian analyses provided evidence that FA and AVE did not predict CMDs risk factors. Conclusions and implications:While facial asymmetry and averageness may influence perceptions of health, they are unlikely to serve as biomarkers of CMDs risk in older women.
Lay Summary Mental health problems vary widely across cultures, yet evolutionary psychiatry has rarely studied non-industrialized societies. This special issue includes four papers—on cross-cultural measurement, mourning rituals in Kenya, perinatal mental health, and post-traumatic stress disorder among Turkana warriors—that begin to fill that gap.
Background:Testosterone is hypothesized to influence energetic tradeoffs between male reproduction and immune function. Testosterone is generally thought to be immunosuppressive, with high testosterone levels signaling male health and infection resistance. The Immunocompetence Handicap Hypothesis (ICHH) posits that testosterone's role in developing male secondary sexual characteristics and suppressing immune function creates a tradeoff between testosterone-linked traits and immunocompetence. Yet, the immune effects of testosterone in humans remain poorly understood. Research is particularly limited among energetically constrained, natural fertility populations characterized by high pathogen loads and long-lasting infections (such as parasitic disease), characteristics relevant to the evolution of hypothesized testosterone-linked tradeoffs. Methods:We test whether salivary testosterone concentrations are associated with parasitic helminth infection status and parasite load among 90 Indigenous Shuar males aged 12-67 years. Results:Higher testosterone levels were associated with increased infection risk but lower parasite load. However, these findings were only evident among adolescents (ages 12-19) and only for Trichuris trichiura (whipworm) but not Ascaris lumbricoides (roundworm) infections. Conclusions:These findings suggest higher testosterone may increase the risk of becoming infected with some parasite species, but that heavy pathogen loads lead to a shift in resource allocation from testosterone production to immune activity during a life stage with high testosterone-related energetic demands. While some results aligned with the ICHH, the significant effects of participant age and parasite species on testosterone-infection associations indicate that the ICHH does not completely capture the full complexity of human immune-related life history tradeoffs and variation in host-parasite interactions.
Background and objectives:Applying social learning biases to healthcare decision-making may help explain why some people decide not to adopt health interventions. Traits like market integration and traditionalism can shape social learning biases, particularly in small scale populations with little formal education and distrust of outgroup populations. This study investigates the role of these features on social learning biases across four different health interventions among Himba pastoralists of northern Namibia. Methodology:Using vignettes from 473 participants sampled in 16 communities, we compare three social learning biases (conformity, prestige bias, parochialism) in four novel healthcare interventions. Participants completed a set of questions to estimate traditionalism and market integration. Multilevel models compared the impact of these variables on the probability of adopting the healthcare interventions. Results:Across social learning biases, conformity showed the strongest effect on likelihood of adoption, whereas we found no difference in the prestige bias condition (compared to conformity). More market integrated participants were more likely to adopt interventions, whereas more traditional participants were less likely to adopt when the outgroup advocated adoption or when most of the community didn't adopt the intervention. Conclusions and implications:These results indicate conformity biases play a strong role in considerations about novel health interventions in indigenous communities, but also that traditional values are instrumental in shaping social learning biases. While previous focus has centered on market integration as a key predictor, we found the degree of traditionalism to be a critical and thus far underappreciated factor in mediating social learning.
Background:Globally, subsistence-level societies are experiencing rapid urbanization and concomitant increases in cardiometabolic diseases. Generalized measures to quantify lifestyle transitions will facilitate the identification of the most potent drivers of changing health within and between populations, enabling the identification of vulnerable communities, and aiding in the creation of effective policies to minimize disease. Methods:We developed ten scales a priori to quantify unique facets of lifestyle (e.g. urban infrastructure, market integration) from cross-sectional data in two Indigenous, transitioning subsistence groups undergoing rapid change in very different ecological and sociopolitical contexts: Turkana pastoralists of northwest Kenya (n = 3692) and Orang Asli mixed subsistence practitioners of Peninsular Malaysia (n = 1119). We tested the extent to which these lifestyle scales predicted 16 measures of cardiometabolic health in each group. We also used factor analysis to decompose lifestyle data post hoc into salient axes, sensitivity analyses to identify the most important drivers of health, and sex-stratified analyses to investigate whether facets of lifestyle differentially impacted cardiometabolic health among males and females. Results:Cardiometabolic health was best predicted by measures that quantified urban infrastructure and market-derived material wealth compared to metrics encompassing diet, mobility, or acculturation, and these results were highly consistent across Turkana and Orang Asli and across sexes. Factor analysis results were also highly consistent between the two groups, revealing that lifestyle variation decomposes into two distinct axes-representing the built environment and diet-which change at different paces and have different relationships with health. Conclusion:Our analyses revealed surprising generalizability: in both the Turkana and Orang Asli, measures of local infrastructure and built environment better predicted cardiometabolic health than other facets of lifestyle that are seemingly more proximate to health, such as diet. We hypothesize that this is because the built environment impacts unmeasured proximate drivers like physical activity and broader access to market goods, and because it serves as a proxy of duration of market integration. Our results support the usage of relatively simple and easy to characterize features of the built environment as a cross-cultural tool in the investigation of lifestyle impacts on cardiometabolic health. Lay Summary:Worldwide, Indigenous and subsistence-level societies are undergoing rapid urbanization, industrialization, and market integration. To facilitate comparative and within-population analyses of resulting changes in health, we developed ten scales that quantify different features of lifestyle change that occur during this transition. We find that cardiovascular and metabolic health were most strongly explained by measures of the built environment, and these findings were highly consistent across two groups-the Turkana of Kenya and Orang Asli of Peninsular Malaysia-living in highly different environments and experiencing distinct pathways to industrialization.
Background and objectives Infection with multiple genetically distinct Plasmodium falciparum parasites is common in human malaria cases. Within an infected patient, a particular genotype may thrive, influencing its chance of transmission. Competitive growth assays provide a quantitative index to assess relative dynamic fitness disparities among co-infecting parasites across experimentally controlled, physiologically relevant conditions to test specific hypotheses. The ability to assess the relative competitive fitness of parasite genotypes present in patient-derived samples will be particularly valuable to track the spread of partial artemisinin (ART) resistance now emerging in Africa.Methodology Pairwise competitive growth outcomes of genetically distinct ART-resistant (ART-R) and ART-sensitive clones isolated from the Thailand-Myanmar border were evaluated after perturbation with dihydroartemisinin. Fluorescent labeled microsatellite markers were used to measure the relative growth densities of each competing parasite. Resistant and susceptible clones were mixed and grown alone in the presence and absence of drug to determine dynamic fitness relationships among the co-infecting parasites.Results ART-R strains demonstrate a competitive advantage when grown in the presence of a high drug dose. However, the loss of this advantage varies in the absence of drug, producing a range of fitness phenotypes for sensitive and resistant strains.Conclusions and implications Not surprisingly, drug-resistant parasites outcompete susceptible parasites under drug; however, additional variables influence whether resistant parasites ultimately prevail when drug is removed, suggesting independent or interacting genetic mechanisms. Knowing relative fitness advantages and costs of specific genotypes can inform how they will spread and evolve in a competitive environment, directing novel intervention strategies.Lay Summary Malaria infections often contain both drug-resistant and drug-sensitive parasites. Parasites were co-grown with and without antimalarials and competitive outcomes varied: sometimes resistant parasites won, sometimes sensitives parasites won, and in one case, the winner changed with antimalarial treatment. Drug-resistant parasite success depends on competing parasites, complicating the prediction of resistance spread.
Evolutionary mismatches between the reproductive life histories of women in industrialized societies and their Paleolithic ancestors are established risk factors for gynecological pathologies and breast cancer. In contemporary women, these include earlier menarche, delayed first full-term pregnancy, and reduced or absent lactation. Hormonal contraceptives lower the risks of ovarian and endometrial cancers by suppressing ovulation and modulating menstruation, and next-generation female contraceptives, including non-hormonal approaches, should aim to retain these non-contraceptive benefits. With careful design, non-hormonal contraceptives could further improve outcomes by reducing breast cancer risk, which may be variably elevated with oral contraceptive use. Importantly, these principles also have implications for male contraception, where preserving endocrine balance while achieving effective fertility control remains a central challenge. Evolutionary medicine provides a useful framework for developing contraceptives that optimize both reproductive and long-term health outcomes.
Background and objectives The relationship between daughters-in-law (DIL) and mothers-in-law (MIL) is often portrayed as conflictual, though from an evolutionary perspective, the two women could cooperate to gain Darwinian fitness benefits. We investigated this relationship in a society where it is central to women's social niche. Without asking directly, we aimed to evaluate markers of conflict and harmony in households, and whether variability in this balance was reflected in differential health outcomes. We also tested whether conflict was less likely in households with more children, and hence greater shared genetic interest.Methodology We studied 110 co-resident DIL-MIL dyads from rural lowland Nepal and compared anthropometry, physical and mental health, lived experience, agency, and attributed contributions to household tasks.Results Overall, DIL had better mental health than MIL, and greater weight and height. Tension over childcare and resting was common. Mental health and height differences within dyads were greater in households with inferred conflict over childcare, compared to inferred harmony households. DIL had better health outcomes and higher weight and height relative to MIL if they lived in conflict compared to harmony households, whereas MIL had better health outcomes if they lived in harmony households. Number of children did not predict conflict.Conclusions and implications Despite MIL being senior in the household, DIL reported lower stress and better mental health, especially in households with inferred conflict. DIL in such households also had better nutritional status. Having had time since marriage to consolidate their status in the household, DIL may have increased their agency and power.Lay summary Our study in rural Nepal aimed to identify which of daughter-in-law or mother-in-law held the upper hand in the household hierarchy, and how this was reflected in health outcomes. Although mothers-in-law are more senior, daughters-in-law had better physical and mental health, especially in households with inferred conflict over childcare.
Background:Obesity is a global health challenge prevalent in Samoa. However, the influence of obesity on adult male reproductive health in Samoa is poorly understood. Objectives:To determine if reproductive hormone levels differed between adult Samoan males with and without obesity. Methodology:Reproductive hormones (follicle stimulating hormone [FSH], luteinizing hormone [LH], inhibin b) and sex hormone binding globulin (SHBG) were compared between non-diabetic adult males in Samoa with and without obesity to test the hypothesis that obesity is associated with compromised reproductive function in this population. Metabolic hormones (insulin, leptin, adiponectin), fasting glucose, age, and anthropometrics were assessed and included in multivariable models. Results:Males with obesity exhibited higher FSH (P = 0.002), lower inhibin b (P = 0.004) and lower SHBG (P < 0.0001). LH levels were similar (P = 0.43). Significant associations were evident between LH and FSH (obesity: r2 = 0.19, P = 0.003; without obesity: r2 = 0.24, P = 0.001), inhibin b and FSH (obesity: r2 = 0.21, P = 0.002; without obesity: r2 = 0.02, P = 0.41), and LH and SHBG (obesity: r2 = 0.25, P = 0.0005; without obesity: r2 0.01, P = 0.49). Multivariable models revealed insulin as an important contributor to inhibin b levels in all males. Conclusions:Obesity status is an important factor in variation in male reproductive hormone profiles in adult Samoan males. Implications:Obesity has potentially negative effects on male reproductive hormone function in Samoa. While the effects on male fertility remain unclear, further research is merited.
Background and objectives:Life history enlightened therapies (LHETs) were originally developed in cancer to combat therapeutic resistance by targeting pathological cell state transitions that enable evolutionary rescue and adaptation to therapy. In this paper, we expand the scope of LHETs to cancer prevention, namely, metabolic dysfunction-associated steatohepatitis (MASH)-induced hepatocellular carcinoma (HCC) initiation. We focus on endocycling, a process wherein cells undergo whole-genome duplication via mitotic skipping, as a keystone life history transition that promotes HCC initiation. Methodology:A key obstacle to LHET translation is the lack of systematic methods that capture cellular life histories and their molecular drivers. To address this gap, we introduce cell cycle mapping, a technique that integrates in situ multiplexed immunofluorescence imaging with manifold learning to visualize the life history of proliferating cells and proteins involved in transitions to pathological cell states. Results:Mathematical modeling demonstrated how endocycling can create an environment that promotes HCC initiation and revealed the potential for endocycle-targeting therapies to prevent HCC. Using cell cycle mapping on human MASH liver tissues, we identified the molecular factors that drive pathological endocycling (Wee1, CDK2, and RAIDD), providing new therapeutic targets for pre-clinical investigation. Conclusions and implications:This application illustrates how cell cycle mapping can uncover key proteins that drive disease-associated cell state transitions and broaden the scope of LHETs from therapy resistance to cancer prevention. More broadly, our study establishes a generalizable pipeline for inferring the life history of cells in diseased tissues and potential interventions for disease management.
Background and objectives:One Paleopathology is a novel concept in Paleopathology that extends the One Health paradigm into the past. A workshop at the University of Durham, UK, was held prior to the 2024 International Society for Evolution, Medicine, and Public Health (ISEMPH) meeting, firstly to define and expand the concept of One Paleopathology and secondly to generate transdisciplinary research and outreach under this framework. This article presents a logic model to evaluate how effectively the workshop met its goals. Methodology:Two surveys were conducted, one immediately following the workshop and at the 1-year mark. These surveys assess the direct outputs from the workshop-tangible research and outreach products-as well as changes in participants' attitudes toward One Paleopathology and the degree to which transdisciplinarity was incorporated into resulting projects. Results:Both the outputs (direct products of the workshop activities) and outcomes (changes in knowledge or attitude because of the activities) of the workshop suggest that the goals are being met. The first goal, to define and expand the concept of One Paleopathology, was met, with participants expressing strong acceptance of the framework. The second goal-generating transdisciplinary research-is reflected in eight ongoing projects initiated at the workshop. Conclusions and implications:The workshop structure and outcomes assessment presented here evaluate an initial effort in effecting conceptual change in the social sciences. Participants were enthusiastic about One Paleopathology, and over the following year new collaborations and research agendas aligned with the concept emerged. Importantly, participants reported integrating transdisciplinarity into their long-term research, indicating that the workshop had a sustained impact.
Background and objectives:The use of psychoactive substances appears to be a consistent behavior throughout human evolutionary history. In contemporary research, this is often attributed to the addictive properties of such substances; an evolutionary perspective offers a more nuanced view. We take the case of betel nut use in Bangladesh to investigate the relationship between betel quid and chronic health outcomes, and to consider local disease ecology and evolutionary explanations for consumption of this psychoactive substance. Methodology:We analyzed data from a random sample of 765 women and 499 men in Matlab, Bangladesh, to assess associations between betel quid use and anemia, type 2 diabetes (T2D), hypertension, and inflammation (C-reactive protein, CRP). Results:Betel quid use was associated with all health outcomes investigated. Use of betel quid was inversely associated with CRP (β = -0.34; P-value = .007). For other outcomes, there were important interactions between betel quid use and gender. A positive association with anemia (aOR: 2.56, CI: 1.62, 4.04) and inverse associations with diabetes and hypertension (aOR: 0.38, CI: 0.22, 0.66; aOR: 0.41, 1.03, respectively) were apparent among men, but not women (anemia: aOR: 1.03, CI: 0.72, 1.49; diabetes: aOR: 0.98, CI: 0.58, 1.65; hypertension: aOR: 1.25, CI: 0.85, 1.85). Conclusions and implications:Betel quid use was inversely associated with inflammation and, among men, positively associated with anemia and inversely associated with diabetes and hypertension. Together, these findings suggest that the use of betel quid, and possibly other addictive substances, may have been a behavioral adaptation to diverse socioecological challenges.
Background and objectives:Somatic mutation patterns in cancer remain largely unexplored outside humans, despite their significance for aging and oncogenesis. Chimpanzees (Pan troglodytes), sharing >98% genomic similarity with humans, display markedly different cancer spectra. To gain comparative insights into cancer susceptibility and resistance, we sequenced chimpanzee hepatocellular carcinoma (HCC) genomes and analyzed their mutational profiles alongside human counterparts. Methodology:HCC and matched non-cancerous tissues from five chimpanzees were examined using histopathology, immunohistochemistry (β-catenin, ARID1A, TSC2, FAP, vimentin, TGF-β), whole-genome sequencing (one pair), and whole-exome sequencing (four pairs). Somatic variants were identified with GATK MuTect2, annotated with Ensembl VEP, and analyzed for functional enrichment. Comparative analyses were performed with subsets of human HCC datasets (TCGA, ICGC) including TSC2-positive and TSC2-negative cases. Results:Chimpanzee HCCs exhibited histological and immunohistochemical features similar to human tumors but displayed sharply divergent genomic landscapes. Chimpanzee tumors carried significantly higher coding mutation loads (mean 5632 per sample vs. 96-275 in humans). Non-synonymous TSC2 mutations occurred in 80% of chimpanzees, versus ~7% in human HCC, suggesting a species-specific oncogenic pathway linked to the scirrhous subtype. Additional recurrently mutated genes included ARID1A, FAT1-4, TP53, and FGA . Despite greater heterogeneity in chimpanzee tumors, humans showed stronger enrichment of non-synonymous single nucleotide variants, implying more intense positive selection. Shared alterations across species involved canonical drivers such as TP53, CTNNB1, FAT4, and TTN. Conclusions and implications:Chimpanzee HCCs are defined by high mutational burden and frequent TSC2 alterations, contrasting with the more selectively constrained mutation spectrum of human HCC. Divergent evolutionary patterns highlight species-specific oncogenic routes while underscoring conserved pathways. Comparative primate cancer genomics offers novel insights into cancer evolution, biomarkers, and therapeutic targets.
Comparative phylogenetics provides a wealth of computational tools to understand evolutionary processes and their outcomes. Advances in these methodologies have occurred in parallel with a surge in cross-species genomic and phenotypic data. To date, however, the majority of published studies have focused on classical questions in evolutionary biology, such as speciation and the ecological drivers of trait evolution. Here, we argue that evolutionary medicine in general, and our understanding of the origin and diversification of disease traits in particular, would be greatly expanded by a wider integration of phylogenetic comparative methods (PCMs). We use comparative oncology-the study of cancer across the tree of life-as an example to demonstrate the power of the approach and show that implementing PCMs can highlight the mode and tempo of the evolutionary changes in intrinsic, species-level disease vulnerabilities.
Multicellularity evolved independently several times across the tree of life. In all cases, these events were dependent on various types of cellular cooperation. We previously identified five universal foundations of cellular cooperation that are required in all complex multicellular lineages to allow the collection of cells to function and reproduce as a whole (i.e. a multicellular individual). These include: proliferation inhibition, controlled cell death, resource allocation, division of labor, and maintenance of the extracellular environment. We propose that there is a sixth universal foundation of multicellularity that breaks down in cancer: proximity maintenance. By staying in close proximity, cells can more easily provide benefits for one another, communicate, coordinate their behavior, and evolve increased size and complexity. Here, we revisit and further develop the five original foundations of multicellular cooperation in the context of the evolution of multicellularity from unicellular ancestors and their implications for cancer progression. In our previous work, we suggested that the breakdown of all these cooperative behaviors is reflected in the universal hallmarks of cancer. Similarly, the breakdown of proximity maintenance maps to another hallmark of cancer—activating invasion and metastasis.
