Sleep and ageing: why does our sleep get worse with age?

Welcome to this edition of?Sleepletter?where we offer you easy-to-read insights from the latest research papers from the field of sleep neurobiology and clinical sleep medicine. We hope you enjoy the content!

Sleep and ageing

All of us appreciate a good night’s sleep. Feeling refreshed and with our batteries fully charged, we are ready to take on (almost) any challenge the day brings. The frustrating part is, though, that sleep quality declines with age. Studies have suggested that this decline starts as early as young adulthood, although it is most evident after the age of 50. People go through well characterized changes in sleep quality and quantity during ageing. Many start going to bed earlier and also wake up earlier (advanced sleep timing) with overall shorter sleep duration. It usually takes more time to fall asleep, and sleep itself is more fragmented with increased number of awakenings, arousals, or transitions to lighter sleep stages. The overall amount of deep sleep, which makes you feel refreshed the next day, is reduced, and the time spent in lighter sleep stages is increased . Naps also become more frequent , with 25% of people aged 75-84 regularly taking daytime naps, up from 10% between the ages of 55 and 64. This deteriorating quality of sleep and increased daytime sleepiness are one of the most prevalent complaints that come with ageing.

Regardless of age, poor sleep quality disrupts many cognitive processes, impairs memory, and increases the risk of numerous cardiovascular, neurological, and psychiatric disorders. But why does sleep become worse as we age? Apart from some evidence that neurons die within certain regions of the brain’s cortex and subcortical areas which might affect sleep, the underlying mechanisms are not well understood.

A new target of interest to elucidate why sleep quality deteriorates with age has been found in hypocretin/orexin neurons. This small group of about 20 000 neurons (the brain has 80+ billion neurons) located in the hypothalamus produces a neuropeptide called hypocretin (or orexin) which promotes wakefulness. Damage to these neurons is the cause of narcolepsy, a disorder characterized by overwhelming daytime drowsiness and sudden attacks of sleep. Studies in rats have shown that the number of hypocretin/orexin neurons is reduced by 40% in older animals. While the effect is much smaller in humans, there is still a 10% reduction observed in old age. Larger effects were observed in patients with tauopathies, disorders such as Alzheimer’s that are characterized by accumulation of misfolded tau protein in the brain, which might explain why sleep disorders are common in neurodegenerative disorders.?

A new study in Science , however, observed hypocretin/orexin neurons from a new angle: focusing not on the raw number of neurons, but their excitability. Researchers conducted a study in mice and observed that older mice exhibited more sleep fragmentation and a considerable loss of hypocretin/orexin neurons. These neurons were more active during sleep in old mice which increased the chance of brief arousals causing sleep fragmentation. When looking into their excitability, they found that that it was considerably increased. The “culprit” was found in a subpopulation of potassium channels (KCNQ2/3)?usually found in neurons. When the researchers pharmacologically activated these neuronal channels, thus repolarizing or “deactivating” neurons, sleep was more consolidated. Using?filorexant, an orexin antagonist used in narcolepsy, which blocks activity of orexin neurons, also increased the time spend in sleep. Taken together, these results indicate that increased excitability of hypocretin/orexin neurons might be the reason why sleep is much more fragmented in older people.?

As promising as these findings are, this still has to be tested in humans, and if proven true, therapies that reduce the activity of hypocretin neurons might be a valuable asset in consolidating sleep in older adults. Until then, however, we will live in hope that our neurons do not misbehave as we get older.??

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About the author

Alen Juginovi??is a medical doctor and postdoctoral researcher in the Department of Neurobiology at Harvard Medical School in Boston, MA, USA studying the effect of poor sleep quality on health. He is also organizing international award-winning projects such as Nobel Laureate conferences, international congresses, concerts and other, as well as participating in many events as a speaker. Feel free to contact him via LinkedIn for any inquiries.