Animal study suggests inadequate sleep may exacerbate cellular aging in the elderly

June 27, 2008

Researchers at the University of Pennsylvania School of Medicine have shown that the unfolded protein response, which is a reaction to stress induced by sleep deprivation, is impaired in the brains of old mice.

The findings suggest that inadequate sleep in the elderly, who normally experience sleep disturbances, could exacerbate an already-impaired protective response to protein misfolding that happens in aging cells. "Protein misfolding and aggregation is associated with many diseases like Alzheimer's and Parkinson's," notes first author Nirinjini Naidoo, PhD, Assistant Professor in the Division of Sleep Medicine. The study appears in the June issue of the Journal of Neuroscience.

The unfolded protein response (UPR) is one part of the quality control system for monitoring protein synthesis in the endoplasmic reticulum, the cellular compartment where some proteins are made. In this study, researchers found that the UPR was activated in 10-week old, sleep-deprived mice, so that misfolded proteins did not accumulate in the endoplasmic reticulum of brain cells in the cerebral cortex. However, in two-year-old, sleep-deprived mice, the UPR failed to do its job and misfolded proteins clogged the endoplasmic reticulum. Old mice that were not stressed by sleep deprivation were shown to already have an impaired UPR.

Sleep in mice is characterized by short periods of inactivity throughout the day and night. On average, mice sleep approximately one hour for every two they are awake. In order to deprive mice of sleep, researchers constantly monitored and gently stroked the mice with a brush to disturb periods of inactivity.

At 3, 6, 9, or 12 hours of sleep deprivation, proteins were examined from the mouse brains. By six hours of sleep deprivation, young mice demonstrated that the UPR system was in place because protein synthesis was shut off by a chaperone protein called BiP/GRP78. In contrast, there was no BiP/GRP78 in old mice so protein synthesis continued.

Old mice also had less of the proteins that refold abnormal proteins than young mice, and old mice had more of the proteins that cause cell death than young mice. Thus, several processes are upset in old mouse brains by sleep deprivation, and the overall result is a further accumulation of misfolded proteins.

"We could speculate that sleep disturbance in older humans places an additional burden on an already-stressed protein folding and degradation system," says Naidoo.

Future studies will examine whether augmenting key protective proteins delays the effects of aging and reduces sleep disturbances.

Source: University of Pennsylvania School of Medicine

Explore further: First human gene implicated in regulating length of human sleep

Related Stories

Sleep loss linked to increase in Alzheimer's plaques

September 24, 2009

Chronic sleep deprivation in a mouse model of Alzheimer's disease makes Alzheimer's brain plaques appear earlier and more often, researchers at Washington University School of Medicine in St. Louis report online this week ...

Hormone links sleep, hunger and metabolism, researchers find

November 14, 2007

While investigating how the hormone orexin might control sleep and hunger, researchers at UT Southwestern Medical Center have discovered, to their surprise, that it activates a protein, HIF-1, long known to stimulate cancerous ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.