Biologists have known for decades that enduring a short period of mild stress makes simple organisms and human cells better able to survive additional stress later in life. Now, scientists have found that a cellular process called autophagy is critically involved in providing the benefits of temporary stress. The study, published in Nature Communications, creates new avenues to pursue treatments for neurological disorders such as Huntington’s disease.

Autophagy is a means of recycling cells’ old, broken, or unneeded parts so that their components can be re-used to make new molecules or be burned for energy. The process had previously been linked to longevity. The new results suggest that long life and stress resistance are connected at the cellular level.

The scientists incubated C. elegans — tiny roundworms used to study fundamental biology — at 36 °C, significantly above the temperature they are usually kept at in the laboratory, for one hour. After this short heat exposure—a mild form of stress that improves the organism’s survival—autophagy rates increased throughout the worms’ tissues. When they exposed these heat-primed worms to another, longer heat shock a few days later, worms that were deficient in autophagy failed to benefit from the initial mild heat shock, as observed in heat-primed worms with intact autophagy.

The researchers reasoned that a mild heat stress might also improve the worms’ ability to handle another condition that worsens with age—buildup of aggregated proteins, which is stressful for cells. To test this hypothesis, they used worms that model Huntington’s disease, a fatal inherited disorder caused by neuronal proteins that start to stick together into big clumps as patients age, leading to degeneration throughout the brain. Exposing worms that make similar sticky proteins in different tissues to a mild heat shock reduced the number of protein aggregates, suggesting that a limited amount of heat stress can reduce toxic protein aggregation.

The researchers say that their findings could suggest new paths to slowing a range of neurodegenerative diseases, including Huntington’s disease, Alzheimer’s disease, and Parkinson’s disease.

Paper “Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans”
Reprinted from materials provided by Sanford Burnham Prebys Medical Discovery Institute