Another Potential Approach to Boosting Cellular Housekeeping

One of the reasons that work on heat shock proteins are attracting interest in the research community is that these proteins are deeply involved in cellular housekeeping processes. They are one of the components of the machinery of hormesis, wherein the body is improved by mild stress and a little cellular damage, because that stress causes repair and housekeeping systems to spring to life and work earnestly to make everything shipshape. Heat shock proteins are so named because they were first identified in the response to molecular damage caused by heat - but they are brought into play by all sorts of stresses that can cause damage to the delicate protein machinery of cells.

As is the case for autophagy, it is worth thinking about where we might be taken by the ability to boost the heat shock response on demand, or selectively alter and improve it. Beyond thoughts on slowing aging, calorie restriction mimetics, and modestly increasing human longevity, a number of mainstream research groups investigate housekeeping mechanisms as a possible way to treat neurodegenerative diseases. I noticed another example of this sort of work recently:

Protecting Cells: Evidence Found for a Neuronal Switch to Prevent Neurodegenerative Diseases

Neurodegenerative diseases, ranging from Huntington's and Parkinson's to amyotrophic lateral sclerosis and Alzheimer's, are believed to stem from early events that lead to an accumulation of damaged proteins in cells. Yet all animals, including humans, have an ancient and very powerful mechanism for detecting and responding to such damage, known as the heat shock response.

"Why are these diseases so widespread if our cells have ways to detect and prevent damaged proteins from accumulating? Can our body fix the problem? That is the conundrum. In our study, much to our surprise, we discovered that the nervous system sends negative signals to other tissues in the animal that inhibit the ability of cells to activate a protective heat shock response. The machinery to repair the damaged proteins is intact, but the nervous system is sending a signal that prevents it from doing its job."

When the signal from the nervous system was reduced, the cells' heat shock response returned, leading to elevated levels of special protective proteins, called molecular chaperones, that kept the damaged proteins in check

This is early stage work in nematode worms: we'll have to wait a few years to see how well it carries through into mice, let alone people.


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