{"title":"一个综合的模型,为支持稳态睡眠信号的聚合生物学提供支持","authors":"Fabian-Xosé Fernandez , Michael A. Grandner","doi":"10.1016/j.sleep.2025.106723","DOIUrl":null,"url":null,"abstract":"<div><div>Sleep has long been understood as a process regulated primarily by central mechanisms, including homeostatic pressure and circadian rhythms. However, emerging research reveals that skeletal muscle actively participates in sleep regulation, functioning as an endocrine organ that releases bioactive molecules capable of influencing brain function. This review examines the growing body of evidence supporting a muscle-derived contribution to sleep homeostasis, focusing on key signaling molecules such as interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), irisin, lactate, and methylglyoxal. We explore their molecular pathways, receptor interactions, and integration with well-established central regulators of sleep, including adenosine and cytokine signaling networks. Compelling genetic evidence, particularly from studies manipulating <em>Bmal1</em> expression specifically in muscle, demonstrates that peripheral tissues can modulate sleep depth and recovery independently of the brain's central mechanisms. These findings support the idea that skeletal muscle functions as a systemic sensor of fatigue, relaying metabolic and inflammatory cues to the brain that help calibrate sleep need. Recognizing this muscle–brain crosstalk opens new directions for translational research, including exercise-based therapies and pharmacological strategies targeting myokine pathways to enhance sleep quality. This evolving perspective challenges the traditional view of sleep as a process governed solely by the brain, positioning skeletal muscle as an active and essential regulator of sleep–wake dynamics.</div></div>","PeriodicalId":21874,"journal":{"name":"Sleep medicine","volume":"134 ","pages":"Article 106723"},"PeriodicalIF":3.4000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A comprehensive model for the converging biologies that underpin the homeostatic sleep signal\",\"authors\":\"Fabian-Xosé Fernandez , Michael A. Grandner\",\"doi\":\"10.1016/j.sleep.2025.106723\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Sleep has long been understood as a process regulated primarily by central mechanisms, including homeostatic pressure and circadian rhythms. However, emerging research reveals that skeletal muscle actively participates in sleep regulation, functioning as an endocrine organ that releases bioactive molecules capable of influencing brain function. This review examines the growing body of evidence supporting a muscle-derived contribution to sleep homeostasis, focusing on key signaling molecules such as interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), irisin, lactate, and methylglyoxal. We explore their molecular pathways, receptor interactions, and integration with well-established central regulators of sleep, including adenosine and cytokine signaling networks. Compelling genetic evidence, particularly from studies manipulating <em>Bmal1</em> expression specifically in muscle, demonstrates that peripheral tissues can modulate sleep depth and recovery independently of the brain's central mechanisms. These findings support the idea that skeletal muscle functions as a systemic sensor of fatigue, relaying metabolic and inflammatory cues to the brain that help calibrate sleep need. Recognizing this muscle–brain crosstalk opens new directions for translational research, including exercise-based therapies and pharmacological strategies targeting myokine pathways to enhance sleep quality. This evolving perspective challenges the traditional view of sleep as a process governed solely by the brain, positioning skeletal muscle as an active and essential regulator of sleep–wake dynamics.</div></div>\",\"PeriodicalId\":21874,\"journal\":{\"name\":\"Sleep medicine\",\"volume\":\"134 \",\"pages\":\"Article 106723\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Sleep medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1389945725003983\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sleep medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1389945725003983","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
A comprehensive model for the converging biologies that underpin the homeostatic sleep signal
Sleep has long been understood as a process regulated primarily by central mechanisms, including homeostatic pressure and circadian rhythms. However, emerging research reveals that skeletal muscle actively participates in sleep regulation, functioning as an endocrine organ that releases bioactive molecules capable of influencing brain function. This review examines the growing body of evidence supporting a muscle-derived contribution to sleep homeostasis, focusing on key signaling molecules such as interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), irisin, lactate, and methylglyoxal. We explore their molecular pathways, receptor interactions, and integration with well-established central regulators of sleep, including adenosine and cytokine signaling networks. Compelling genetic evidence, particularly from studies manipulating Bmal1 expression specifically in muscle, demonstrates that peripheral tissues can modulate sleep depth and recovery independently of the brain's central mechanisms. These findings support the idea that skeletal muscle functions as a systemic sensor of fatigue, relaying metabolic and inflammatory cues to the brain that help calibrate sleep need. Recognizing this muscle–brain crosstalk opens new directions for translational research, including exercise-based therapies and pharmacological strategies targeting myokine pathways to enhance sleep quality. This evolving perspective challenges the traditional view of sleep as a process governed solely by the brain, positioning skeletal muscle as an active and essential regulator of sleep–wake dynamics.
期刊介绍:
Sleep Medicine aims to be a journal no one involved in clinical sleep medicine can do without.
A journal primarily focussing on the human aspects of sleep, integrating the various disciplines that are involved in sleep medicine: neurology, clinical neurophysiology, internal medicine (particularly pulmonology and cardiology), psychology, psychiatry, sleep technology, pediatrics, neurosurgery, otorhinolaryngology, and dentistry.
The journal publishes the following types of articles: Reviews (also intended as a way to bridge the gap between basic sleep research and clinical relevance); Original Research Articles; Full-length articles; Brief communications; Controversies; Case reports; Letters to the Editor; Journal search and commentaries; Book reviews; Meeting announcements; Listing of relevant organisations plus web sites.