Fruit Fly Study Connects Sleep, Age and Protein Folding

Staying up all night in college to study for an exam, and then catching up on sleep the next day, is a commonplace occurrence. However, as we age, this ability to recoup lost sleep diminishes.

Researchers at the Perelman School of Medicine, University of Pennsylvania, report that the pathways of aging and sleep intersect at circuitry of a cellular stress response pathway. By manipulating those connections, the researchers were able to alter the sleep pattern in aging fruit flies.

The study, published the journal Neurobiology of Aging, was led by Nirinjini Naidoo, associate professor in the Center for Sleep and Circadian Neurobiology and the Division of Sleep Medicine with the help of postdoctoral fellow Marishka Brown.

The elderly sleep less during the night than the young, and also their sleep quality is worse. Additionally, these older individuals take more naps during the day. Naidoo's lab previously found that aging is associated with the unfolding of proteins, a "hallmark of cellular stress called the unfolded protein response," according to the press release.

By video monitoring young and old fruit flies, the researchers concluded that aged flies took longer to make up lost sleep, slept less overall and had more interrupted sleep sessions. However, after the researchers added a molecular "chaperone" called sodium 4-phenylbutyrate (PBA), which promotes proper protein folding, the older flies showed a more youthful sleep pattern. PBA is currently used to treat Parkinson's and cystic fibrosis.

Moving in the opposite direction, the team gave the young fruit flies tunicamycin, which induces protein misfolding and stress. After being given the tunicamycin, the young flies began to exhibit sleep patterns common to more aged flies.

Speaking about the PBA, Naidoo said the substance increased the total amount of time slept for older flies and shifted recovery sleep to look more like that of a young fly.

"It rescued the sleep patterns in the older flies," she explained.

From the research, the team reached the conclusion that protein misfolding and cellular stress is the result of sleep loss and sleep loss recovery decreases with age. In addition, and more insidious, is the concept that sleep fragmentation leads to cellular stress which is followed by neuronal dysfunction which in turn leads to more sleep fragmentation.

Naidoo hopes that these results can be scaled up to mice and humans to allow drugs such as PBA to break the negative sleep cycle, especially in the aged.

"People know that sleep deteriorates with aging," Naidoo says, "But this might be able to be stopped or reversed with molecular chaperones." Her team is now looking to determine if a similar situation exists in mammals and if better sleep translates into longer lifespan.