Researchers have shown that the unfolded protein response (UPR), a reaction to stress induced by sleep deprivation, is impaired in the brains of old mice. This suggests that inadequate sleep in the elderly could exacerbate an already-impaired protective response to protein misfolding that happens in aging cells.

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.