Cellular senescence is a stress-responsive cell fate characterized by stable growth arrest and acquisition of a proinflammatory senescence-associated secretory phenotype. Senescent cells accumulate with advancing age and contribute to dysfunction and disease across multiple organ systems. In skeletal muscle (SkM), emerging evidence indicates that senescence arises across diverse cell populations that collectively reshape the SkM niche. Through the SASP and altered intercellular signaling, senescent cells promote chronic inflammation, fibrosis, impaired regeneration, and metabolic dysfunction that contribute to SkM loss, SkM weakness, functional decline, and frailty. This review synthesizes current knowledge of the molecular drivers, hallmarks, and cellular origins of senescence within SkM and highlights the physiological consequences that extend from the cellular to the organismal level. We also discuss emerging senotherapeutic strategies that hold promise for optimizing SkM health and function with aging and disease.
Dinosaurs dominated terrestrial ecosystems for more than 160 million years under fluctuating atmospheric conditions that profoundly shaped their cardiovascular physiology. Evidence from phylogenetic bracketing, fossil morphology, and comparative models with crocodilians, birds, and mammals suggests that many dinosaurs possessed a fully separated four-chambered heart capable of sustaining high systemic pressures and efficient oxygen (O 2 ) transport. In sauropods, extreme vertical distances between the heart and brain required arterial pressures exceeding those of any extant vertebrate, raising questions about cardiac structure, ventricular wall stress, and vascular adaptations. Oxygen transport was further modulated by atmospheric O 2 variability across the Mesozoic and therefore sauropods likely managed these changes by shaping their hemoglobin affinity, capillary density, respiratory system, and Bohr and Haldane effects. Mitochondrial density, redox balance, and the regulation of reactive species such as nitric oxide and hydrogen sulfide may have already underpinned thermoregulation, metabolic reprogramming, and tissue energetics. By integrating paleophysiology with modern comparative physiology, this review discusses how informed speculations on sauropods cardiovascular biology may be used to improve our understanding of endothermy, gigantism, and adaptive strategies in variations of O 2 /carbon dioxide environments. We posit that the necessary adaptations of the heart, microcirculation, and pressure–volume relations are relevant for understanding extreme physiology and, in some cases, human cardiovascular disease. This review synthesizes current knowledge on sauropods cardiovascular physiology, focusing on cardiac function, vascular architecture, O 2 transport, and whole-organism integration.
Laboratory rats ( Rattus norvegicus ) have been invaluable to biomedical research and are well-suited for physiological analyses. Nevertheless, technical challenges in embryo and genetic manipulation have historically hindered the generation of genetically modified rats, thereby limiting their use for in vivo functional genetic studies. Recent advances, including genome editing and pluripotent/germline stem cell technologies, have substantially expanded rat genetic engineering. This review summarizes the historical background and recent advances in rat embryo manipulation and highlights the rapid development of genetic tools in rats, now catching up with those available in mice. These advances provide an opportunity to reassess the value of rats as experimental models. Furthermore, the combined use of mice and rats, exemplified by interspecific chimeras and comparative studies, offers new insights into conserved and species-specific physiological mechanisms across mammals.
