Interleukin 6 as an energy allocator in muscle tissue.

Extensive research has shown that interleukin 6 (IL-6) is a multifunctional molecule that is both proinflammatory and anti-inflammatory, depending on the context. Here, we combine an evolutionary perspective with physiological data to propose that IL-6's context-dependent effects on metabolism reflect its adaptive role for short-term energy allocation. This energy-allocation role is especially salient during physical activity, when skeletal muscle releases large amounts of IL-6. We predict that during bouts of physical activity, myokine IL-6 fulfills the three main characteristics of a short-term energy allocator: it is secreted from muscle in response to an energy deficit, it liberates somatic energy through lipolysis and it enhances muscular energy uptake and transiently downregulates immune function. We then extend this model of energy allocation beyond myokine IL-6 to reinterpret the roles that IL-6 plays in chronic inflammation, as well as during COVID-19-associated hyperinflammation and multiorgan failure.

Trunk muscle endurance, strength and flexibility in rural subsistence farmers and urban industrialized adults in western Kenya.

OBJECTIVES: High trunk muscle endurance, strength, and moderate flexibility reportedly help maintain musculoskeletal health, but there is evidence for tradeoffs among these variables as well as sex differences in trunk muscle endurance and strength. To test if these observations extend similarly to both men and women in nonindustrial and industrial environments, we investigated intra-individual associations and group and sex differences in trunk muscle endurance, strength, and flexibility among 74 (35 F, 39 M; age range: 18-61 years) adults from the same Kalenjin-speaking population in western Kenya. We specifically compared men and women from an urban community with professions that do not involve manual labor with rural subsistence farmers, including women who frequently carry heavy loads. METHODS: Trunk muscle endurance, strength, and flexibility were measured with exercise tests and electromyography (EMG). RESULTS: We found a positive correlation between trunk extensor strength and endurance (R = .271, p ≤ .05) and no associations between strength or endurance and flexibility. Rural women had higher trunk extensor and flexor endurance, EMG-determined longissimus lumborum endurance, and trunk extensor strength than urban women (all p ≤ .05). Rural women had higher trunk extensor and flexor endurance than rural men (both p ≤ .05). Urban women had lower trunk flexor and extensor endurance than urban men (both p ≤ .01). CONCLUSIONS: High levels of physical activity among nonindustrial subsistence farmers, particularly head carrying among women, appear to be associated with high trunk muscle endurance and strength, which may have important benefits for helping maintain musculoskeletal health.

The active grandparent hypothesis: Physical activity and the evolution of extended human healthspans and lifespans.

The proximate mechanisms by which physical activity (PA) slows senescence and decreases morbidity and mortality have been extensively documented. However, we lack an ultimate, evolutionary explanation for why lifelong PA, particularly during middle and older age, promotes health. As the growing worldwide epidemic of physical inactivity accelerates the prevalence of noncommunicable diseases among aging populations, integrating evolutionary and biomedical perspectives can foster new insights into how and why lifelong PA helps preserve health and extend lifespans. Building on previous life-history research, we assess the evidence that humans were selected not just to live several decades after they cease reproducing but also to be moderately physically active during those postreproductive years. We next review the longstanding hypothesis that PA promotes health by allocating energy away from potentially harmful overinvestments in fat storage and reproductive tissues and propose the novel hypothesis that PA also stimulates energy allocation toward repair and maintenance processes. We hypothesize that selection in humans for lifelong PA, including during postreproductive years to provision offspring, promoted selection for both energy allocation pathways which synergistically slow senescence and reduce vulnerability to many forms of chronic diseases. As a result, extended human healthspans and lifespans are both a cause and an effect of habitual PA, helping explain why lack of lifelong PA in humans can increase disease risk and reduce longevity.

Geometric morphometric investigation of craniofacial morphological change in domesticated silver foxes.

To test the effects of domestication on craniofacial skeletal morphology, we used three-dimensional geometric morphometrics (GM) along with linear and endocranial measurements to compare selected (domesticated) and unselected foxes from the Russian Farm-Fox Experiment to wild foxes from the progenitor population from which the farmed foxes are derived. Contrary to previous findings, we find that domesticated and unselected foxes show minimal differences in craniofacial shape and size compared to the more substantial differences between the wild foxes and both populations of farmed foxes. GM analyses and linear measurements demonstrate that wild foxes differ from farmed foxes largely in terms of less cranial base flexion, relatively expanded cranial vaults, and increased endocranial volumes. These results challenge the assumption that the unselected population of foxes kept as part of the Russian Farm-Fox experiment are an appropriate proxy for 'wild' foxes in terms of craniofacial morphology and highlight the need to include wild populations in further studies of domestication syndrome to disentangle the phenotypic effects of multiple selection pressures. These findings also suggest that marked increases in docility cannot be reliably diagnosed from shape differences in craniofacial skeletal morphology.

Anti-Müllerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer.

Anti-Müllerian hormone (AMH) and its type II receptor AMHR2, both previously thought to primarily function in gonadal tissue, were unexpectedly identified as potent regulators of transforming growth factor (TGF-ß)/bone morphogenetic protein (BMP) signaling and epithelial-mesenchymal transition (EMT) in lung cancer. AMH is a TGF-ß/BMP superfamily member, and AMHR2 heterodimerizes with type I receptors (ALK2, ALK3) also used by the type II receptor for BMP (BMPR2). AMH signaling regulates expression of BMPR2, ALK2, and ALK3, supports protein kinase B-nuclear factor κB (AKT-NF-κB) and SMAD survival signaling, and influences BMP-dependent signaling in non-small cell lung cancer (NSCLC). AMH and AMHR2 are selectively expressed in epithelial versus mesenchymal cells, and loss of AMH/AMHR2 induces EMT. Independent induction of EMT reduces expression of AMH and AMHR2. Importantly, EMT associated with depletion of AMH or AMHR2 results in chemoresistance but sensitizes cells to the heat shock protein 90 (HSP90) inhibitor ganetespib. Recognition of this AMH/AMHR2 axis helps to further elucidate TGF-ß/BMP resistance-associated signaling and suggests new strategies for therapeutic targeting of EMT.