The Benefits of Hormesis Require Autophagy

Hormesis describes the outcome of a little damage inflicted upon an organism or tissue resulting in a net gain in health and function. Exercise, lack of nutrients, heat, and low levels of toxins or radiation all stress cells, damaging proteins and structures, causing the affected cells to boost their repair and maintenance efforts for some time. If the exposure to damaging circumstances is sufficiently mild and short-lived, then the overall result is an improvement, the additional maintenance activities more than compensating for the damage inflicted. Researchers here demonstrate that this beneficial response requires the cellular recycling process of autophagy, responsible for removing structures and proteins that have become damaged or dysfunctional. The research community has for some time shown an interest in building therapies to slow the progression of aging based on enhancement of autophagy, but beyond calorie restriction mimetic research there has been surprisingly little concrete progress on this front.

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. 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 researchers incubated C. elegans worms 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. "Our finding that brief heat exposure helps alleviate protein aggregation is exciting because it could lead to new approaches to slow the advance of neurodegenerative diseases such as Huntington's. This research raises many exciting questions. For example, how does induction of autophagy by a mild heat stress early on make cells better able to survive heat later - what's the cellular memory? There's a lot to follow up on."

Link: http://www.newswise.com/articles/what-doesn-t-kill-you-makes-you-stronger

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