The endocannabinoid system and the ageing brain.

IF 26.7 1区医学 Q1 Neuroscience

Nature Reviews Neuroscience Pub Date : 2026-10-16 DOI:10.1038/s41583-026-01085-7

Andreas Zimmer

{"title":"The endocannabinoid system and the ageing brain.","authors":"Andreas Zimmer","doi":"10.1038/s41583-026-01085-7","DOIUrl":null,"url":null,"abstract":"<p><p>Ageing is accompanied by a progressive decline in homeostatic resilience that increases vulnerability to chronic disease, disability and cognitive impairment. Although unhealthy brain ageing can often be prevented by managing the underlying risk factors, the molecular, cellular and physiological mechanisms that connect risk factors to late-life brain dysfunction remain incompletely understood. This review examines the role of the endocannabinoid system in brain ageing. The endocannabinoid system is a short-range lipid signalling network that helps to maintain neuronal, glial, metabolic and inflammatory homeostasis. Endocannabinoid signalling follows a dynamic lifespan trajectory, with relatively high activity during early adulthood and functional decline during ageing. Genetic or pharmacological disruption of endocannabinoid system activity impairs several processes linked to hallmarks of brain ageing, including neuroinflammatory control, adult neurogenesis, synaptic plasticity, cognitive performance, metabolic regulation and epigenetic stability. Conversely, low-dose Δ9-tetrahydrocannabinol (THC) treatment can ameliorate several ageing-related brain phenotypes in old animals. However, clinical evidence in older humans remains limited, and the therapeutic potential of cannabinoid-based interventions requires further evaluation.</p>","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":" ","pages":""},"PeriodicalIF":26.7000,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41583-026-01085-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Neuroscience","Score":null,"Total":0}

引用次数: 0

Abstract

Ageing is accompanied by a progressive decline in homeostatic resilience that increases vulnerability to chronic disease, disability and cognitive impairment. Although unhealthy brain ageing can often be prevented by managing the underlying risk factors, the molecular, cellular and physiological mechanisms that connect risk factors to late-life brain dysfunction remain incompletely understood. This review examines the role of the endocannabinoid system in brain ageing. The endocannabinoid system is a short-range lipid signalling network that helps to maintain neuronal, glial, metabolic and inflammatory homeostasis. Endocannabinoid signalling follows a dynamic lifespan trajectory, with relatively high activity during early adulthood and functional decline during ageing. Genetic or pharmacological disruption of endocannabinoid system activity impairs several processes linked to hallmarks of brain ageing, including neuroinflammatory control, adult neurogenesis, synaptic plasticity, cognitive performance, metabolic regulation and epigenetic stability. Conversely, low-dose Δ9-tetrahydrocannabinol (THC) treatment can ameliorate several ageing-related brain phenotypes in old animals. However, clinical evidence in older humans remains limited, and the therapeutic potential of cannabinoid-based interventions requires further evaluation.

查看原文本刊更多论文

内源性大麻素系统和老化的大脑。

随着年龄的增长，体内平衡恢复力逐渐下降，从而增加了患慢性病、残疾和认知障碍的脆弱性。虽然通常可以通过控制潜在的风险因素来预防不健康的大脑老化，但将风险因素与晚年大脑功能障碍联系起来的分子、细胞和生理机制仍然不完全清楚。本文综述了内源性大麻素系统在脑老化中的作用。内源性大麻素系统是一个短距离脂质信号网络，有助于维持神经元、神经胶质、代谢和炎症的稳态。内源性大麻素信号遵循动态的生命轨迹，在成年早期具有相对较高的活性，随着年龄的增长功能下降。内源性大麻素系统活性的遗传或药理学破坏会损害与脑衰老特征相关的几个过程，包括神经炎症控制、成人神经发生、突触可塑性、认知表现、代谢调节和表观遗传稳定性。相反，低剂量Δ9-tetrahydrocannabinol （THC）治疗可以改善老年动物的几种与衰老相关的大脑表型。然而，老年人的临床证据仍然有限，基于大麻素的干预措施的治疗潜力需要进一步评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature Reviews Neuroscience 医学-神经科学

CiteScore

35.00

自引率

0.60%

发文量

104

审稿时长

6-12 weeks

期刊介绍： Nature Reviews Neuroscience is a journal that is part of the Nature Reviews portfolio. It focuses on the multidisciplinary science of neuroscience, which aims to provide a complete understanding of the structure and function of the central nervous system. Advances in molecular, developmental, and cognitive neuroscience have made it possible to tackle longstanding neurobiological questions. However, the wealth of knowledge generated by these advancements has created a need for new tools to organize and communicate this information efficiently. Nature Reviews Neuroscience aims to fulfill this need by offering an authoritative, accessible, topical, and engaging resource for scientists interested in all aspects of neuroscience. The journal covers subjects such as cellular and molecular neuroscience, development of the nervous system, sensory and motor systems, behavior, regulatory systems, higher cognition and language, computational neuroscience, and disorders of the brain. Editorial decisions for the journal are made by a team of full-time professional editors who are PhD-level scientists.