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Metabolic Alterations in HSCs during Aging and Leukemogenesis. 造血干细胞在衰老和白血病发生过程中的代谢改变。
IF 5.3 2区 医学
Physiology Pub Date : 2025-07-01 Epub Date: 2025-02-28 DOI: 10.1152/physiol.00054.2024
Yi-Hsuan Chiang, Stephan Emmrich, Nicola Vannini
{"title":"Metabolic Alterations in HSCs during Aging and Leukemogenesis.","authors":"Yi-Hsuan Chiang, Stephan Emmrich, Nicola Vannini","doi":"10.1152/physiol.00054.2024","DOIUrl":"10.1152/physiol.00054.2024","url":null,"abstract":"<p><p>Aging is a multifaceted process associated with a functional decline in cellular function over time, affecting all lifeforms. During the aging process, metabolism, a fundamental hallmark of life (1), is profoundly altered. In the context of hematopoiesis, the proper function of hematopoietic stem cells, at the apex of the blood system, is tightly linked to their energy metabolism, which in turn shapes hematopoietic output. Here, we review the latest developments in our understanding of the metabolic states and changes in aged hematopoietic stem cells, molecular players and pathways involved in aged hematopoietic stem cell metabolism, the consequences of perturbed metabolism on clonal hematopoiesis and leukemogenesis, and pharmacologic/genetic strategies to reverse or rejuvenate altered metabolic phenotypes.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of Stem Cell Function by NAD. NAD对干细胞功能的调控。
IF 5.3 2区 医学
Physiology Pub Date : 2025-07-01 Epub Date: 2025-02-05 DOI: 10.1152/physiol.00052.2024
Yufan Feng, Huixian Qiu, Danica Chen
{"title":"Regulation of Stem Cell Function by NAD<sup />.","authors":"Yufan Feng, Huixian Qiu, Danica Chen","doi":"10.1152/physiol.00052.2024","DOIUrl":"10.1152/physiol.00052.2024","url":null,"abstract":"<p><p>Nicotinamide adenine dinucleotide (NAD<sup>+</sup>), a coenzyme in cellular metabolism, has never ceased to capture the fascination of scientists since its discovery in 1906. The expansion of NAD<sup>+</sup>'s function from cellular metabolism to DNA repair, gene regulation, cell signaling, and aging reflects the central role of cellular metabolism in orchestrating the diverse cellular pathways. In the past decade, NAD<sup>+</sup> has emerged as a key regulator of stem cells, opening the door to potential approaches for regenerative medicine. Here we reflect on how the field of NAD<sup>+</sup> regulation of stem cells has evolved since a decade ago, when sirtuins, NAD<sup>+</sup>-dependent enzymes, were shown to be critical regulators of stem cells. We review the recent development on how NAD<sup>+</sup> is regulated in stem cells to influence fate decision. We discuss the difference in NAD<sup>+</sup> regulation of normal and cancer stem cells. Finally, we consider the consequences of NAD<sup>+</sup> regulation of stem cells for health and diseases.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
How Is Laughter the Best Medicine? 笑为什么是最好的药？
IF 5.3 2区 医学
Physiology Pub Date : 2025-07-01 Epub Date: 2024-12-26 DOI: 10.1152/physiol.00061.2024
Connor T A Brenna
{"title":"How Is Laughter the Best Medicine?","authors":"Connor T A Brenna","doi":"10.1152/physiol.00061.2024","DOIUrl":"10.1152/physiol.00061.2024","url":null,"abstract":"","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune Aging and Its Implication for Age-Related Disease Progression. 免疫老化及其对年龄相关疾病进展的意义
IF 5.3 2区 医学
Physiology Pub Date : 2025-07-01 Epub Date: 2025-01-31 DOI: 10.1152/physiol.00051.2024
Yuki Sato
{"title":"Immune Aging and Its Implication for Age-Related Disease Progression.","authors":"Yuki Sato","doi":"10.1152/physiol.00051.2024","DOIUrl":"10.1152/physiol.00051.2024","url":null,"abstract":"<p><p>As life expectancy increases globally, the prevalence and severity of age-related diseases have risen, significantly impacting patients' quality of life and increasing dependency on the healthcare system. Age-related diseases share several pathological commonalities, and emerging evidence suggests that targeting these biological processes ameliorates multiple age-related diseases. Immune aging plays a critical role in the pathogenesis of age-related diseases, given its involvement not only in controlling infection and cancer but also in facilitating tissue homeostasis and repair. Aging causes compositional and functional changes in both innate and adaptive immune cells, thereby significantly contributing to the pathogenesis of age-related disease and systemic low-grade inflammation, termed \"inflammaging.\" This review article aims to describe the current understanding of immune aging and its impact on age-related diseases with particular emphasis on kidney and autoimmune diseases. In addition, this review highlights tertiary lymphoid structures (TLS) as a hallmark of immune aging, exploring their roles in inflammation, tissue damage, and potential therapeutic targeting.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transforming Physiology and Healthcare through Foundation Models. 通过基础模型转变生理学和医疗保健。
IF 5.3 2区 医学
Physiology Pub Date : 2025-05-01 Epub Date: 2025-01-20 DOI: 10.1152/physiol.00048.2024
Ryan C Godwin, Avery Tung, Dan E Berkowitz, Ryan L Melvin
{"title":"Transforming Physiology and Healthcare through Foundation Models.","authors":"Ryan C Godwin, Avery Tung, Dan E Berkowitz, Ryan L Melvin","doi":"10.1152/physiol.00048.2024","DOIUrl":"10.1152/physiol.00048.2024","url":null,"abstract":"<p><p>Recent developments in artificial intelligence (AI) may significantly alter physiological research and healthcare delivery. Whereas AI applications in medicine have historically been trained for specific tasks, recent technological advances have produced models trained on more diverse datasets with much higher parameter counts. These new, \"foundation\" models raise the possibility that more flexible AI tools can be applied to a wider set of healthcare tasks than in the past. This review describes how these newer models differ from conventional task-specific AI, which relies heavily on focused datasets and narrow, specific applications. By examining the integration of AI into diagnostic tools, personalized treatment strategies, biomedical research, and healthcare administration, we highlight how these newer models are revolutionizing predictive healthcare analytics and operational workflows. In addition, we address ethical and practical considerations associated with the use of foundation models by highlighting emerging trends, calling for changes to existing guidelines, and emphasizing the importance of aligning AI with clinical goals to ensure its responsible and effective use.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neural Circuits of Fear and Anxiety: Insights from a Neuroethological Perspective. 恐惧和焦虑的神经回路：从神经行为学角度的见解。
IF 5.3 2区 医学
Physiology Pub Date : 2025-05-01 Epub Date: 2024-12-11 DOI: 10.1152/physiol.00042.2024
Fernando Falkenburger Melleu, Newton Sabino Canteras
{"title":"Neural Circuits of Fear and Anxiety: Insights from a Neuroethological Perspective.","authors":"Fernando Falkenburger Melleu, Newton Sabino Canteras","doi":"10.1152/physiol.00042.2024","DOIUrl":"10.1152/physiol.00042.2024","url":null,"abstract":"<p><p>The predatory imminence continuum (PIC) of antipredator defensive behavior has been a helpful strategy for modeling anxiety and fear-related disorders in nonclinical research. The PIC is divided into three different sequential stages that reflect defensive behavioral strategy in response to predatory imminence. However, the PIC was experimentally addressed with a series of shock-based fear conditioning experiments rather than predatory threats. In this article, we consider the PIC in a more naturalistic behavioral setting, focusing on analyzing the neural systems of animals responding to terrestrial and aerial predators. Of relevance, there is a sequential engagement of the distinct neural circuits along each phase of the PIC. In the preencounter phase, prefrontal cortical networks are particularly involved in planning and organizing behavioral responses to ambiguous threats. As the predatory cues or the real predator is detected, there is an engagement of amygdalar and hippocampal > hypothalamic pathways in conjunction with the periaqueductal gray, which organize fear responses. This dynamic particularly reveals how specific neural circuits are set into action to subserve distinct defensive responses. Moreover, we further explore the neural circuits governing other fearful situations outside the context of the PIC, including agonistic social encounters and interoceptive challenges. This analysis reveals an interesting overlap between the neural systems responding to these threats and those involved in response to predatory threats. The present review clarifies how defensive circuits respond to natural threats and provides a more realistic view of the neural systems underlying anxiety and fear responses.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting Sleep Physiology to Modulate Glymphatic Brain Clearance. 以睡眠生理为目标，调节大脑甘油清除。
IF 5.3 2区 医学
Physiology Pub Date : 2025-05-01 Epub Date: 2024-11-27 DOI: 10.1152/physiol.00019.2024
Timo van Hattem, Lieuwe Verkaar, Elena Krugliakova, Nico Adelhöfer, Marcel Zeising, Wilhelmus H I M Drinkenburg, Jurgen A H R Claassen, Róbert Bódizs, Martin Dresler, Yevgenia Rosenblum
{"title":"Targeting Sleep Physiology to Modulate Glymphatic Brain Clearance.","authors":"Timo van Hattem, Lieuwe Verkaar, Elena Krugliakova, Nico Adelhöfer, Marcel Zeising, Wilhelmus H I M Drinkenburg, Jurgen A H R Claassen, Róbert Bódizs, Martin Dresler, Yevgenia Rosenblum","doi":"10.1152/physiol.00019.2024","DOIUrl":"10.1152/physiol.00019.2024","url":null,"abstract":"<p><p>Sleep has been postulated to play an important role in the removal of potentially neurotoxic molecules, such as amyloid-β, from the brain via the glymphatic system. Disturbed sleep, on the other hand, may contribute to the accumulation of neurotoxins in brain tissue, eventually leading to neuronal death. A bidirectional relationship has been proposed between impaired sleep and neurodegenerative processes, which start years before the onset of clinical symptoms associated with conditions like Alzheimer's and Parkinson's diseases. Given the heavy burden these conditions place on society, it is imperative to develop interventions that promote efficient brain clearance, thereby potentially aiding in the prevention or slowing of neurodegeneration. In this review, we explore whether the metabolic clearance function of sleep can be enhanced through sensory (e.g., auditory, vestibular) or transcranial (e.g., magnetic, ultrasound, infrared light) stimulation, as well as pharmacological (e.g., antiepileptics) and behavioral (e.g., sleeping position, physical exercise, cognitive intervention) modulation of sleep physiology. A particular focus is placed on strategies to enhance slow-wave activity during nonrapid eye movement sleep as a driver of glymphatic brain clearance. Overall, this review provides a comprehensive overview on the potential preventative and therapeutic applications of sleep interventions in combating neurodegeneration, cognitive decline, and dementia.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Off to the Races: How the Thoroughbred Is Helping Us Understand Skeletal Muscle. 比赛开始：纯种马如何帮助我们理解骨骼肌。
IF 5.3 2区 医学
Physiology Pub Date : 2025-05-01 Epub Date: 2024-12-26 DOI: 10.1152/physiol.00062.2024
Madison R Barshick
{"title":"Off to the Races: How the Thoroughbred Is Helping Us Understand Skeletal Muscle.","authors":"Madison R Barshick","doi":"10.1152/physiol.00062.2024","DOIUrl":"10.1152/physiol.00062.2024","url":null,"abstract":"","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Histone Deacetylases in Metabolism: the Known and the Unexplored. 代谢中的组蛋白去乙酰化酶：已知与未知。
IF 5.3 2区 医学
Physiology Pub Date : 2025-05-01 Epub Date: 2024-10-29 DOI: 10.1152/physiol.00044.2024
Somaya Y Ibrahim, Jayden Carter, Rushita A Bagchi
{"title":"Histone Deacetylases in Metabolism: the Known and the Unexplored.","authors":"Somaya Y Ibrahim, Jayden Carter, Rushita A Bagchi","doi":"10.1152/physiol.00044.2024","DOIUrl":"10.1152/physiol.00044.2024","url":null,"abstract":"<p><p>Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl groups from key lysine residues on histone and nonhistone proteins and thereby regulate gene transcription. They have been implicated in several biological processes in both healthy and pathological settings. This review discusses the role of HDACs in multiple metabolically active tissues and highlights their contribution to the pathogenesis of tissue-specific maladaptation and diseases. We also summarize the current knowledge gaps and potential ways to address them in future studies.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Multiscale Perspective on Chromatin Architecture through Polymer Physics. 通过聚合物物理学透视染色质结构的多尺度视角
IF 10.3 2区 医学
Physiology Pub Date : 2025-05-01 Epub Date: 2024-11-27 DOI: 10.1152/physiol.00050.2024
Francesca Vercellone, Andrea M Chiariello, Andrea Esposito, Mattia Conte, Alex Abraham, Andrea Fontana, Florinda Di Pierno, Fabrizio Tafuri, Sougata Guha, Sumanta Kundu, Ciro Di Carluccio, Mario Nicodemi, Simona Bianco
{"title":"A Multiscale Perspective on Chromatin Architecture through Polymer Physics.","authors":"Francesca Vercellone, Andrea M Chiariello, Andrea Esposito, Mattia Conte, Alex Abraham, Andrea Fontana, Florinda Di Pierno, Fabrizio Tafuri, Sougata Guha, Sumanta Kundu, Ciro Di Carluccio, Mario Nicodemi, Simona Bianco","doi":"10.1152/physiol.00050.2024","DOIUrl":"10.1152/physiol.00050.2024","url":null,"abstract":"<p><p>The spatial organization of chromatin within the eukaryotic nucleus is critical in regulating key cellular functions, such as gene expression, and its disruption can lead to disease. Advances in experimental techniques, such as Hi-C and microscopy, have significantly enhanced our understanding of chromatin's intricate and dynamic architecture, revealing complex patterns of interaction at multiple scales. Along with experimental methods, physics-based computational models, including polymer phase separation and loop-extrusion mechanisms, have been developed to explain chromatin structure in a principled manner. Here, we illustrate genomewide applications of these models, highlighting their ability to predict chromatin contacts across different scales and to spread light on the underlying molecular determinants. Additionally, we discuss how these models provide a framework for understanding alterations in chromosome folding associated with disease states, such as SARS-CoV-2 infection and pathogenic structural variants, providing valuable insights into the role of chromatin architecture in health and disease.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":10.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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