A Tiny Tweak to Gut Bacteria Can Extend an Animal’s Life

A Tiny Tweak to Gut Bacteria Can Extend an Animal’s Life – The Atlantic – Ed Yong –  JUN 15, 2017

Most of the worms in Meng Wang’s lab die on schedule. They live their brief lives on Petri dishes, and after two to three weeks, they die of old age.

But some individuals beat the odds, surviving for several days longer than usual.These wormy Methuselahs were all genetically identical, so it wasn’t their genes that explained their decelerated aging. Instead, the secret to their longevity lay in the microbes within their gut.

This is part of a growing number of studies showing that an animal’s microbiome—the community of microbes that shares its body—can influence its lifespan.  

Wang had loaded all the worms with the same bacterium—a single strain of the common gut microbe E. coli. But in some of these strains, she had deleted a single gene. That tiny change made all the difference, extending the worm’s lives.

In 2013, Filipe Cabreiroshowed that metformin—a drug that’s used to treat type 2 diabetes, and that’s being investigated for anti-aging properties—lengthens the lives of nematode worms, but only if the worms have microbes in their guts.

More recently, Dario Valenzano showed that the killifish—an extremely short-lived fish that’s being increasingly used in studies of aging—lives longer if old individuals consume the poop of younger ones, suggesting either that old microbiomes quicken the deaths of these fish, or that young microbiomes can prolong their lives.

Despite these promising hints, it’s hard to work out exactly why and how the microbiome influences the pace of aging, because these communities can be bewilderingly complex.

When you have a huge range of microbe species exchanging an even wider range of chemicals, it’s hard to tell which particular bug or molecule is important.

So Wang decided to sweep that complexity aside and focus on a very simple partnership. Her team member Bing Han started with a library of E. coli strains that were each missing a single gene, but were otherwise identical.

He then fed these strains to the nematode C. elegans—a small transparent worm that features heavily in aging research, and whose body and genes have been thoroughly characterized.

Of the 4,000 or so E. coli strains, Han found that 29 extended the worms’ lives by at least 10 percent.

And 19 of these “also protected the worms from age-associated diseases” like cancer and neurodegenerative conditions, says Wang. “They lived longer and better.”

Several of these life-extending bacterial strains behaved predictably—they influenced networks of worm genes that are already known to influence the aging process.

But two strains did something unexpected.  

Their missing genes are involved in making colanic acid—a type of sugar found on the surface of many gut microbes.

And these particular microbes, because of their deleted genes, were producing unusually large amounts of colanic acid. And when Han stopped them from doing so, they no longer extended the worms’ lives. Colanic acid was the key.

The team also found some hints about how colanic acid works. Very few people have studied this molecule, but it seems to affect the worm’s mitochondria—bean-shaped structures that live inside animal cells and provide them with energy.

Colanic acid stimulates these tiny power plants to split apart, making extra copies of themselves.

It also switches on a group of genes that help mitochondria deal with stressful conditions, and that have been previously linked to longer life in worms. For reasons that are still unclear, these actions seem to put more sand in the worms’ hourglasses

Mitochondria are former microbes themselves.

They descend from a free-living bacterium that found its way into another microbe and stayed there, becoming a permanent source of energy for the host.

That event happened billions of years ago, but mitochondria still retain traces of their former lives as bacteria. And it’s clear that modern bacteria can influence them. “It’s just amazing to me that after so many years of separation, they can still talk to each other,” Wang says.

the team has already shown that colanic acid can also extend the life of fruit flies, and can affect the mitochondria of mammalian cells in the same way that it did those of the worms. “I don’t want to speculate too much, but that makes us positive,” Wang says. “We’re now starting experiments with mice.”

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