Circadian Rhythms in Aging and Age-Related Neurogenerative Disease

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.