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Even if science can’t make life longer, perhaps a pill can make a long life better

10:52am, June 17, 2013
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To live long and prosper (physically, not financially), you’d probably rather take a pill than starve yourself. So far, though, most of the evidence says very-low-calorie diets are the best strategy for living a longer life. At least if you’re a worm or a fly.

It hasn’t been established that less food means a longer life for people. Still, the possible life-extending effects of drastic diets have scientists salivating over the prospect of a pill that could mimic the benefits of caloric restriction. Even if such a pill can’t make you live longer than a normal life span, it could help you live better, at least as far as your brain is concerned.

Such pills might help preserve mental prosperity in old age, a number of studies indicate. Some research suggests that eating substantially less than normal ameliorates factors linked to brain degeneration disorders such as Alzheimer’s, for instance. Other new work focuses on why some people’s brains age without mental decline. Figuring out why some brains age successfully might lead to strategies for helping those that don’t.

In one new study, mice were given a treatment that causes nerve cells in the brain to die. Some mice were then put on a low-cal diet; they lost substantially fewer cells than mice that were fed normally. And the hungry mice also showed higher performance on tests of mental ability.
“Without affecting the animals’ general behavior, the regimen of caloric restriction specifically improved ... object recognition memories,” MIT neuroscientist Johannes Gräff and colleagues write in the May 22 Journal of Neuroscience.

Further tests showed that the low-cal diet boosted levels of sirtuin 1, an enzyme implicated by some studies as a factor in enhancing life span. If sirtuin 1 helps protect against nerve cell degeneration, then it stands to reason that raising sirtuin 1 levels would promote a healthy brain. So Gräff and collaborators tried a substance known to activate the gene responsible for making sirtuin 1. That substance, SRT3657, was given orally to mice that had also been given a nerve cell killer. SRT3657 reduced brain damage just as caloric restriction had.

“SRT3657 recapitulated the beneficial effects of caloric restriction against neurodegeneration-associated pathologies and thus might constitute a pharmacological alternative to caloric
restriction,” the MIT scientists wrote.

This work is just in mice, of course. It’s too soon to say whether similar success will be seen in humans. And other questions remain, such as whether the sirtuin-activating drug has bad side effects that would negate its benefit for the brain. It’s also not clear whether the drug must be taken before nerve cell loss begins or if it can stop degeneration after it has started.

Furthermore, fighting off disease-related degeneration is not the only issue. Fading mental abilities often accompany aging in normal healthy brains. Degraded mental functioning such as the loss of memory skill is common in people as they grow older, even without the onset of severe diseases such as Alzheimer’s.

Yet not all people suffer substantial mental decline as they age. Some “successful agers” maintain high levels of mental performance as long as they live, even into their 90s. Scientists have debated whether those successful agers develop a way to compensate for aging declines that afflict everybody, or whether they instead simply preserve brain power that others lose.

Over a period of 15 to 20 years, scientists at Umea University in Sweden repeatedly tested memory ability in more than 1,500 people (ages 35 to 80) to identify individuals whose brainpower diminished the least. Of those, 51 were tested in brain scanners, as were those in a matched group of 51 that had shown average loss of mental ability during the study period.

After extensive statistical massaging of the data to correct for any spurious influences, the researchers concluded that the successful group had preserved activity in key parts of the brain that had deteriorated in the average group. There was some evidence that the high performers among the aged had also possessed higher mental ability to begin with. But the statistics would not permit a firm conclusion on that point, Sara Pudas and colleagues write in the May 15 Journal of Neuroscience.

Perhaps factors that promote successful mental aging do so by helping to maintain activity in the hippocampus and prefrontal cortex, the brain areas identified as crucial in this study. Some of those beneficial factors are not easily adjusted (such as being female or possessing a particular version of an important gene), the researchers point out. But living with somebody and being physically active, both linked to successful brain aging, are plausible strategies for most people.

Of course, these latest studies are just a small part of the voluminous research literature on these topics. The full picture on aging and the brain is still a little fuzzy. But recent progress seems promising. Someday getting old might no longer be so closely linked to intellectual decline. And when Vulcans say live long and prosper, they’ll mean mentally as well as physically.

Follow Tom Siegfried on Twitter at @tom_siegfried.

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