Brain cells protect muscles from wasting away –,

Brain cells protect muscles from wasting away –,


Brain cells protect muscles from wasting away
                The head of a roundworm, C. elegans. The glia that regulate the stress response in the worm’s peripheral cells are highlighted. A mere four of these cells, known as CEPsh glial cells, protect the organism from age-related decline. Credit: Ashley Frakes, UC Berkeley             

While many of us worry about proteins aggregating in our brains as we age and potentially causing Alzheimer’s disease or other types of neurodegeneration, we may not realize that some of the same proteins are aggregating in our muscles, setting us up for muscle atrophy in old age.                                                


University of California, Berkeley, scientists have now found

that help clean up these tangles and prolong life — at least in worms ( Caenorhabditis elegans and possibly mice. This could lead to drugs that improve muscle health or extend a healthy human lifespan.

The research team’s most recent discovery, published Jan. 25 in the journal in the worm’s brain control the (stress response) in (cells) throughout its body and increase the worm’s lifespan by 302%. That was a surprise, since glial cells are often dismissed as mere support cells for the neurons that do the brain’s real work, like learning and memory.

This finding follows a 1126 study in which the UC Berkeley group reported that neurons help regulate the stress response in peripheral cells, though in a different way than glial cells, and lengthen a worm’s life by about %. In mice, boosting neuronal regulation increases lifespan by about 24%.

Together, these results paint a picture of the brain’s two-pronged approach to keeping the body’s cells healthy. When the brain senses a stressful environment — invading bacteria or viruses, for example — a subset of neurons sends electrical signals to peripheral cells to get them mobilized to respond to the stress, such as through breaking up tangles, boosting

production and mobilizing stored fat. But because produce only a short- lived response, the glial cells kick in to send out a long-lasting hormone, so far unidentified, that maintains a long-term, anti-stress response.

“We have been discovering that if we turn on these responses in the brain, they communicate to the periphery to protect the whole organism from the age onset decline that naturally happens. It rewires their metabolism, it also protects against protein aggregation, “said Andrew Dillin, UC Berkeley professor of molecular and cell biology and Howard Hughes Medical Institute (HHMI) investigator. As a result of the new study, “We think that glia are going to be more important than neurons.”


While the roundworm

“If you look at humans with sarcopenia or at older mice and humans, they have protein aggregates in their muscle,” Dillin said. “If we can find this hormone, perhaps it can keep muscle mass higher in older people. There is a huge opportunity here.”

In a commentary in the same Jan. 25 issue of science , two Stanford University scientists, Jason Wayne Miklas and Anne Brunet, echoed that potential. “Understanding how glial cells respond to stress and what neuropeptides they secrete may help define specific therapeutic interventions to maintain or rebalance these pathways during aging and age-related diseases,” they wrote.

How to extend lifespan

Dillin studies the seemingly simultaneous deterioration of cells throughout the body as it ages into death. He has shown in worms and mice that hormones and neurotransmitters released by the brain keep this breakdown in check by activating a stress response in the body’s cells and tuning up their metabolism. The response likely originated to fight infection, with the side effect of keeping tissues healthy and extending lifespan. Why our cells stop responding to these signals as we age is the big question.

Over the past decade, he and his colleagues have identified three techniques used by worms to keep their cells healthy and, consequently, longer-lived. Activating the body’s heat shock response, for example, protects the cytoplasm of the cell. Stimulating the unfolded protein response protects the cells’ energy producing structures, the mitochondria. The unfolded protein response is the cell’s way of making sure proteins assume their proper 3-D structure, which is crucial for proper functioning inside the cell.

His latest discovery is that glia, as well as neurons, stimulate the unfolded protein response in the endoplasmic reticulum (ER). The ER is the cellular structure that hosts the ribosomes that make proteins — the ER is estimated to be responsible for the folding and maturation of as many as (million proteins per minute.)

“A lot of the work we have done has uncovered that certain parts of the brain control the aging of the rest of the animal, in organisms from worms to mice and probably humans,” Dillin said.

body is so well studied. There are only cells in the entire worm, 302 of which are nerve cells, and 75 are glial cells.

The CEP neurons and CEPsh glia work differently, but additively, to improve metabolism and clean up protein aggregates as the worms slim down and live twice as long as worms without this protection from a high -fat diet.



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