Aging is older than you think

Scientists used to think that E. coli (shown above, dividing) did not age, but new research suggests they do, meaning aging has deeper evolutionary roots than once thought. (Janice Haney Carr)

E. coli used to be immortal.

To be precise, many scientists did not believe that this gut microbe got old. E. coli - along with other bacteria - simply grew until they were ready to divide. Where one microbe had been, there were two new ones, each ready to grow and divide again.

But recent research has found that E. coli does not enjoy eternal youth. Over time, some of the bacteria become decrepit and lose the ability to make quick, flawless copies of themselves.

The discovery suggests that aging is a universal property of life.

And it also opens up a new front in the search for anti-aging medicines. In E. coli and humans alike, defective clumps of proteins seem to be responsible for the effects of aging. If scientists can find a way to prevent the damage that old E. coli sustains, they may be able to use that knowledge to fight aging in humans.

"We think it has a reasonable chance," says Eric Stewart, a microbiologist at Northeastern University who has led the research on aging in E. coli.

Most research on aging in the past has focused on humans and other animals. For people, aging appears to be the result of damage that gradually accumulates in cells over a person's lifetime. Gene sequences get garbled, for example, and proteins become damaged and take on defective shapes. Cells have a more difficult time carrying out their functions and grow more and more slowly.

Yet cells also have a remarkable capacity to repair themselves. They can proofread DNA and destroy defective proteins, replacing them with new ones. So why hasn't evolution favored perfect repair - in other words, immortality?

"Immortality is not cost-effective," says Stewart.

To never get old, organisms would have to invest a huge amount of energy in repair. They'd be left with little energy to reproduce. Natural selection would instead favor other organisms that put less energy into repair and produced more offspring.

A common solution to this trade-off is to set aside a special population of cells that will reproduce. Our bodies put a great deal of energy into keeping eggs and sperm from becoming damaged. They put much less care into repairing the rest of our cells.

"My children are born young and rejuvenated. So the damage of my aging is kept just to me," says Stewart.

Animals share this strategy. So do fungi. A single-celled yeast buds off new yeast cells, and over time the "parent" yeast begins to show signs of aging, accumulating damage and reproducing more slowly. In 2003, scientists found a species of bacteria that also got old. Known as Caulobacter crescentus, it also reproduces by budding. And like yeast, the parent cell divides more slowly as it produces more offspring.

But unlike Caulobacter, most bacteria divide into two seemingly identical clones. Many scientists assumed that symmetrically dividing microbes could not take advantage of the aging strategy we use. "Every problem that would arise, the cell would have to fix," says Stewart.

Stewart and his colleagues have revealed that even symmetrically dividing bacteria get old.

They put a single E. coli on a slide and allowed it to reproduce. They engineered it to produce a glow, which made it and its descendants easier to film. Using sophisticated image-processing software, they were able to track 35,000 cells, observing how long each one took to divide.

In 2005, Stewart and his colleagues reported that some bacteria began to reproduce more slowly than their cousins, and over the generations their descendants slowed down even more.

There was one crucial difference between the old and young microbes: the caps at each end of their rod-shaped bodies. Each time E. coli divides, the two new microbes each inherit one of its caps, and the microbe must manufacture a new cap for each one. When these two microbes divide again, they each make two new caps. Over the generations, there will be some bacteria that inherit the original caps from the common ancestor of the entire colony, while others have younger caps. After a cap ages for 100 generations, the scientists estimate, the cell can no longer reproduce.

The scientists then took a closer look at what was happening inside the bacteria. Earlier this year, they reported that clumps of tangled proteins grow in E. coli. As the bacteria divide, these clumps end up in the old caps. Somehow, the defective proteins help slow down the growth of old bacteria.

Stewart sees these results as evidence that single-celled bacteria use the same strategy multicellular animals do to cope with cell damage.

"It's probably cheaper to throw away your garbage in one cell while the rest of your population grows."

Daniel Promislow, an expert on the genetics of aging at the University of Georgia, finds the research exciting. For one thing, it suggests that the common ancestor of bacteria and animals was already aging 3 billion years ago.

"Aging would be a really old phenomenon," he says.

Studying aging in quick-breeding E. coli could allow scientists to get answers about the process faster than with other lab animals, like flies or mice, Promislow says. "There's a lot you can do in a short amount of time."

It might even be possible to translate some of those lessons to medical applications. Alzheimer's disease, for example, is associated with clumps of proteins called plaques that form in neurons.

"It may be possible to find a way to alleviate protein damage in E. coli that would have a use in higher organisms," says Stewart. "I'm not saying it's going to be easy to find, though."

Carl Zimmer, a Connecticut-based science writer, is the author of "Microcosm: E. coli and the New Science of Life," among other books.