Protein Misfolding and Reversal of Age-Related Sleep Issues
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An interesting relationship between cellular maintenance machinery and age-related issues with sleep is uncovered and partially reversed by researchers here - though I would like to see more work on this topic before going along with their interpretation as to what is happening under the hood:

[Scientists] have been studying the molecular mechanisms underpinning sleep. Now they report that the pathways of aging and sleep intersect at the circuitry of a cellular stress response pathway, and that by tinkering with those connections, it may be possible to alter sleep patterns in the aged for the better - at least in fruit flies.

Increasing age is well known to disrupt sleep patterns in all sorts of ways. Aging is associated with increasing levels of protein unfolding, a hallmark of cellular stress called the "unfolded protein response." Protein misfolding is also a characteristic of several age-related neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and as it turns out, also associated with sleep deprivation. [The researchers] wanted to know if rescuing proper protein folding behavior might counter some of the detrimental sleep patterns in elderly individuals.

They found that aged flies took longer to recover from sleep deprivation, slept less overall, and had their sleep more frequently interrupted compared to younger control animals. However, adding a molecule that promotes proper protein folding - a molecular "chaperone" called PBA - mitigated many of those effects, effectively giving the flies a more youthful sleep pattern. PBA (sodium 4-phenylbutyrate) is a compound currently used to treat such protein-misfolding-based diseases as Parkinson's and cystic fibrosis. Molecular analysis of sleep-deprived and PBA-treated flies suggested that PBA acts through the unfolded protein response.

The team also asked the converse question: Can protein misfolding induce altered sleep patterns in young animals. Another drug, tunicamycin, induces protein misfolding and stress, and when the team fed it to young flies, their sleep patterns shifted towards those of aged flies, with less sleep overall, more interrupted sleep at night, and longer recovery from sleep deprivation.

Link: http://www.eurekalert.org/pub_releases/2014-02/uops-sif022014.php

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