Aging is known to disrupt sleep patterns in all sorts of ways. Elderly people sleep at night less than their younger counterparts and also sleep less well. Older individuals also tend to nap more during the day. The laboratory of Nirinjini Naidoo, PhD, research associate professor in the Division of Sleep Medicine, has reported that sleep loss/ deprivation increases the levels of misfolded proteins leading to, cellular stress and the “unfolded protein response”. Dr. Naidoo’s lab also showed that this response is impaired with age in both the brain and pancreas. By examining pancreatic tissues in older mice subjected to sleep deprivation, Naidoo discovered signs of extreme cellular stress and loss of cells, affecting the body's ability to maintain proper blood sugar levels.

Protein misfolding is a characteristic of several age-related neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Using a video monitoring system to compare the sleep habits of “young” (9–12 days old) and “aged” (8 weeks old) fruit flies, Naidoo found that aged flies took longer to recover from sleep deprivation, slept less overall, and had their sleep more frequently interrupted compared to younger animals. However, adding a molecule that promotes proper protein folding – a molecular “chaperone” called 4-phenylbutyrate (PBA) -- mitigated many of those effects, effectively giving the flies a more youthful sleep pattern. The team also asked the converse question: Can protein misfolding induce altered sleep patterns in young animals? Tunicamycin, a drug that induces protein misfolding and stress, was fed to young flies. This drug shifted the sleep patterns of the young flies towards those of aged flies; leading to less sleep overall, more interrupted sleep at night and longer recovery from sleep deprivation. PBA, Naidoo says, had two effects on aged flies: it “consolidated” baseline sleep, increasing the total amount of time slept and shifted recovery sleep, after sleep deprivation, to look more like that of a young fly.

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