Zitting Kirsi-Marja, Yuan Robin K
Department of Medicine and Neurology, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
Curr Sleep Med Rep. 2025 Dec;11(1). doi: 10.1007/s40675-025-00336-w. Epub 2025 May 17.
Age-related changes in the circadian timing system may play a role in the development of disorders in older age. We review key aspects of the human circadian system that change with aging, discuss recent evidence of how changes in sleep and circadian rhythms manifest in neurodegenerative diseases, and summarize research on new therapies.
Several mechanisms have been proposed to underlie age-related changes in sleep and circadian rhythmicity. These mechanisms include changes in the suprachiasmatic nucleus, melatonin production, and light sensitivity as well as impaired glymphatic drainage, buildup of amyloid-beta, hypoxia from sleep-disordered breathing, and increased levels of orexin. While light-based therapies and lifestyle interventions have been under investigation for years, newer interventions include treatment with orexin antagonists and gamma stimulation to improve sleep and circadian rhythmicity.
Despite growing interest, our understanding of how sleep and circadian rhythms contribute to the development of age-related neurodegenerative diseases is still limited. More research is needed to understand the bidirectional relationship between circadian rhythms, sleep, and neurodegenerative diseases to develop targeted interventions.
昼夜节律系统的年龄相关变化可能在老年人疾病的发生发展中起作用。我们综述了人类昼夜节律系统随衰老而发生变化的关键方面，讨论了睡眠和昼夜节律变化在神经退行性疾病中表现的最新证据，并总结了新疗法的研究情况。
已提出多种机制来解释与年龄相关的睡眠和昼夜节律变化。这些机制包括视交叉上核的变化、褪黑素分泌、光敏感性，以及脑脊液淋巴引流受损、β-淀粉样蛋白积聚、睡眠呼吸紊乱导致的缺氧和食欲素水平升高。虽然基于光的疗法和生活方式干预已经研究多年，但新的干预措施包括使用食欲素拮抗剂和伽马刺激来改善睡眠和昼夜节律。
尽管关注度不断提高，但我们对睡眠和昼夜节律如何导致年龄相关神经退行性疾病的理解仍然有限。需要更多研究来了解昼夜节律、睡眠和神经退行性疾病之间的双向关系，以制定有针对性的干预措施。
