IBNS-CMEDIA: An analysis of biological clocks throughout the human body suggests that too few hours of sleep—and too many—may speed ageing in the brain, heart, lung, and immune system and is associated with a wide range of diseases.
“Previous studies have found that sleep is largely linked to ageing and the pathological burden of the brain. Our study goes further and shows that too little and too much sleep are associated with faster ageing in nearly every organ, supporting the idea that sleep is important in maintaining organ health within a coordinated brain-body network, including metabolic balance, and a healthy immune system,” says study leader Junhao Wen, assistant professor of radiology at Columbia University Vagelos College of Physicians and Surgeons.
The research was published May 13 in Nature, according to the Columbia University Irving Medical Center website.
The power of ageing clocks
Ageing clocks are increasingly popular for digitising how many years a person ages faster or slower than their chronological age using machine learning, based on biological data (e.g., proteins from a minimally invasive blood test).
Though most ageing clocks measure ageing across the whole body, organs age at different rates (a fact well-known to women facing ticking biological clocks due to fast-ageing ovaries).
Wen’s group has been at the forefront of constructing ageing clocks for specific organs in the body that could provide more specific and personalised information to patients.
“Everyone is excited by these ageing clocks and their ability to predict disease and mortality risk,” Wen says, “but to me, the more exciting question is, can we link ageing clocks to a lifestyle factor that can be modified in time to slow ageing?”
U-shaped patterns between ageing clocks and sleep
Sleep was the perfect test case, as sleep is increasingly thought to be an important factor in health. “I’m also a light sleeper and was getting worried about the effects on myself,” says Wen.
To build his ageing clocks, Wen used data collected from half a million participants in the UK Biobank and used machine learning to determine signatures for an ageing organ. Wen used a wide variety of data sources to create ageing clocks based on structural data from medical images, organ-specific proteins, and molecules found in blood from each organ. “In the liver, for example, we have an ageing clock built with protein data, an ageing clock of metabolic data, and an ageing clock of imaging data,” Wen says. “This allows us to see whether sleep is distinctively associated with ageing clocks derived from multiple omics and molecular layers.”
Wen then assessed the relationship between a person’s sleep duration (as reported by each Biobank participant) and their biological ages from 23 ageing clocks across 17 organ systems.
Across the entire body, a coordinated U-shaped pattern emerged: In the UK Biobank population, both short sleep (fewer than 6 hours) and long sleep (greater than 8 hours) were associated with faster ageing, while the least amount of ageing occurred in people who reported between 6.4 and 7.8 hours of sleep per day. This does not mean that sleep duration alone causes organs to age faster or slower, but it suggests that both insufficient and excessive sleep may be markers of poorer overall health across the body.
Sleep’s body-wide connection to disease
The relationship between sleep and disease suggests that there exists a connection between the brain and the body that extends beyond merely influencing the brain itself.
Among brain-related disorders, short sleep was significantly associated with depressive episodes and anxiety disorders, as seen in other studies of sleep and mental health. Short sleep was also associated with obesity, type 2 diabetes, hypertension, ischemic heart disease, and heart arrhythmias. Short and long sleep were associated with chronic obstructive pulmonary disease, asthma, and a cluster of digestive disorders, including gastritis and gastroesophageal reflux disease.
Wen says, “The broad brain-body pattern is important because it tells us that sleep duration is a deeply embedded part of our entire physiology, with far-reaching implications across the body.”
A deeper look at late-life depression and sleep
Beyond predicting disease, the organ-specific ageing clocks are also valuable for determining how sleep is related to specific conditions, as exemplified by Wen’s examination of late-life depression.
Although the study could not definitively determine if sleep duration caused late-life depression or if late-life depression impacted sleep duration, Wen’s group applied “mediation analysis” to late-life depression, asking whether ageing clocks mediate the relationship between both short and long sleep and late-life depression. The analyses suggest that short sleep may act directly on the disease burden of late-life depression, while long sleep may impact late-life depression via a mediation pathway underlying the brain and adipose clocks.
“This has a strong implication for future sleep management and future therapeutics,” Wen says. “Our study suggests there may be different biological pathways between long and short sleepers that lead to the same outcome, late-life depression, and we shouldn’t treat them the same way.”
