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Brain chemicals help worms live long and prosper

Serotonin and dopamine accompany life span extension in nematodes on a diet

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5:00pm, March 11, 2014

LOW CAL  Unlike normal worms, calorie-restricted C. elegans maintain high levels of the brain chemicals serotonin and dopamine, a new study finds. 

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The fabled elixir of life delivers eternal youth free from the bodily indignities that come with age. In reality, worms on a restricted diet also live long, healthy lives, thanks to high levels of certain neural chemicals, a new study suggests.

Unlike their normal counterparts, worms on a diet maintain high levels of serotonin and dopamine as they get older, scientists report in the March 12 Journal of Neuroscience. But calorie restriction wasn’t necessary to get some benefits: Extra serotonin on its own seemed to provide behavioral improvements and a modest life span boost.

It’s too early to say whether the results hold true for other animals, but there are hints that the brain’s serotonin and dopamine machinery goes awry in people as the years advance.

The worm results may help clarify which physiological changes can actually influence the aging process and which are just along for the ride, says geneticist Michael Petrascheck of the Scripps Research Institute in La Jolla, Calif., who was not involved in the research. “The question is, ‘Which ones really do matter?’ ” The new study suggests that in some cases, these brain chemicals are one potential answer, he says.

Researchers led by Shi-Qing Cai of the Chinese Academy of Sciences in Shanghai noticed that in the roundworm Caenorhabditis elegans, old age came with diminished levels of serotonin and dopamine. These neurotransmitters help neurons send a wide variety of signals, some of which involve mood, pleasure, movement and eating. But a similar decline wasn’t present in worms that carried a mutation making them inefficient eaters. (The mutation, in the eat-2 gene, extended worm life span by about 50 percent in previous experiments.)

Other sorts of long-living worms, such as those with altered mitochondria or insulin-sensing proteins, didn’t maintain high levels of dopamine and serotonin into old age. Something particular to a restricted diet allowed worms to keep neurotransmitter levels high.

But worms didn’t have to eat less to get some benefits. Worms genetically altered to produce more serotonin throughout their lives showed improved feeding and mating behavior and a slightly longer life span than usual, Cai and colleagues found. On average, these worms lived 24 days, while normal worms lived 22 days. Worms that ate and absorbed serotonin late in life also showed behavioral improvements and lived slightly longer lives than normal, the team found. Extra dopamine led to better behavior but didn’t extend life span.

Human studies suggest that serotonin and dopamine messages start to deteriorate beginning in middle age, Cai says. These changes may contribute both to movement problems that come with age, such as difficulty walking and rigidity, and to more complex brain problems such as memory trouble, he says.

Most studies on aging focus on life span alone, Cai says, but “being healthy and living longer are equally important for elderly people.” The new results in worms may provide a clue in the quest for healthier, longer lives, he says.

Petrascheck cautions that while the results are interesting, much of how the body and brain age remains mysterious — particularly in people. “I wouldn’t say we’re even close to understanding what drives aging,” he says. “There is still a lot to be learned.”  

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