Evolution, Medicine, and Public Health最新文献

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.

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.

Our ability to define the causes of aging could enable targeted interventions to extend healthspan. Classical evolutionary models based on individual age have provided critical insights into empirical trajectories of aging; however, gaps remain. We argue that technological advances in data capture, resolution, and scale present a rich opportunity to shed light on heterogeneity in patterns of aging. Computational and data analysis advances have produced expanded theoretical models that explicitly address details of the underlying biology, introducing variables and dynamics that go beyond 'age' itself. We argue that by incorporating richer biological detail to create more integrative predictive models, we can gain insight into expected future distributions of aging within populations, and better understand the molecular and demographic context in which selection has given rise to variability in aging. We provide an overview of existing models that address heterogeneity, and outline future directions and applications that would advance this key area in aging and biomedical research.

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.

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.