Sustaining quality of life with age

Coleen Murphy, an assistant professor of genomics and molecular biology, has a cartoon on her office door that shows a scientist holding an Erlenmeyer flask filled with a mysterious liquid. “It may very well bring about immortality,” the scientist tells a colleague. “But it will take forever to test it.”

Though Murphy studies aging and its genetic underpinnings, she does not expect to face the cartoon scientist’s eternal dilemma. Her aim is to understand the genes that contribute to quality of life, not just the ones that prolong it. Murphy’s lab studies biological processes that decline before death — specifically, reproduction, learning, and memory — in C. elegans, a tiny worm commonly used in biology labs. Learning about the genes that govern those activities in worms could help to identify analogous genes in humans.

At just one millimeter in length, a single C. elegans looks, to the naked eye, like an unremarkable speck of dust. But the little worms, Murphy says, are powerful models for research on aging. Their multicellular bodies provide more complexity than single-cell models like yeast and bacteria, and their short life span (normally two to three weeks) enables researchers to do experiments relatively quickly.

In one project, Murphy has taken a closer look at how the ability of C. elegans to reproduce declines with age. Using a finding from a study of genes in mice as a starting point, her lab regulated the same genes in C. elegans and doubled the amount of time in which the worms can reproduce. Murphy and her students are screening genes to find others that also could play an important role in reproduction. “We don’t think of [reproduction] normally as an aging process,” she says. “But if you back up, you find that for women, the first noticeable, age-related process that declines is reproduction.”

To study learning and memory in C. elegans, Murphy’s lab had developed a feeding method that encourages the worms to make a Pavlovian association between food and an unrelated chemical odor. In time, the worms become drawn to the odor, even when there is no food present. But the long-term memory that enables that association — one of the worm’s most complex functions — declines just a few days into the worm’s life, long before it shows other indications of aging, like slower body movements. By screening for those worms that maintain memory longer than their contemporaries, Murphy hopes to find the genes that extend memory function.

How much can scientists extrapolate from the life of a millimeter-long worm? Certainly there are limits, Murphy says. But there are some processes and genes that are conserved in evolution — the connection between the reproduction genes in C. elegans and mice is just one of many examples. Each study of model organisms brings scientists closer to understanding topics in human health, like age-related diseases, and Murphy’s lab is developing new techniques, using DNA microarrays, robotics, and automated imaging, to accelerate the rate of discovery.

“The real area we’re interested in is maintaining function with age,” Murphy says. “The whole idea of decline, that it’s necessary with age — I think that could be questioned.”