Fighting Against Time

Researchers help worm fight aging; Will it help humans some day?

April 17, 2007

By Russ Hudson

Caenorhabditis elegans, or C. elegans.
It is a common, one millimeter long—not quite microscopic—worm found in soil and rotting trees. Barely noticeable.

But, this tiny creature shares about 40 percent of the same DNA as humans and it ages like a human. It loses muscle mass and its functions decline.

It has a relatively short life span—ordinarily less than three weeks—so it can be carefully observed throughout its lifecycle. That is essential, because the goal of the National Institutes of Health-funded research being conducted by Chandra Srinivasan, assistant professor of biochemistry at Cal State Fullerton, and her student researchers in the Dan Black Hall laboratory is to explore the antioxidant properties of manganese supplements … including how long manganese can extend the lives of the little nematodes (round worms).

Some day, it could have applications to humans and how long they live.

Fifteen percent
“Sixteen to 18 days,” said Srinivasan. “That’s the standard life span of a normal C. elegans. Then we included the mineral, manganese, as a supplement in their diets and they lived about 15percent longer. We added even more manganese, thinking we’d see toxicity from that level of manganese. Instead, they lived a little longer, even.” For humans, that can mean more than 12 years.

“We even used C. elegans that were identified by other labs as having genetic defects that shortened their lives by several days. Again, manganese helped them to live about 15 percent longer,” Srinivasan said.

Srinivasan is not alone in this research. Thousands of scientists, including those at such places as Harvard, Stanford, MIT, Buck Institute, Johns Hopkins and UCLA, are trying to find out what can add years to the human life span. Some of those labs are also looking at manganese “But we are the first group to start using multicellular organisms for this particular research,” Srinivasan said. “Others are using bacteria or yeast.” Her lab is the first to show that manganese is beneficial to C. elegans, she said.

Collaboration
Srinivasan collaborates with a number of other research groups, including those at Johns Hopkins and UCLA. She also gives talks and presentations frequently on her work, including a recent talk, by invitation, at Claremont McKenna College.

Among those in the lab with the assistant professor are sophomore biochemistry student Kim Trinh, junior biology major Alvaro Villarreal, senior biology major Richard Parenteau, fourth-year biology major Stephanie Sprowl, fifth year biology and psychology major Keyan Matinpour and graduate biochemistry student Natalie Rangel. Srinivasan said she attempts to have students from every year, including graduates, working with her at the same time. That way the students can help guide each other and, when they graduate, they are fully familiar with the principles of research.

In fact, Rangel co-authored two papers on the research, “Measuring “free” iron levels in Caenorhabditis elegans using low-temperature Fe(III) electron paramagnetic resonance spectroscopy” in Analytical Biochemistry in November 2006, and “Manganous Ion Supplementation Accelerates Wild-Type Development, Enhances Stress Resistance and Rescues the Life-Span of a Short–Lived Caenorhabditis elegans Mutant” in Free Radical Biology and Medicine in December 2005.

The supposition being explored is that manganese helps the worms resist the free radicals that promote aging. Free radicals are chemical compounds in the body with an unstable number of electrons. Free radicals, because of their instability, can chemically react with cellular components in the body, causing damage. That damage, as it collects over time, is a major contributor to the aging process.

Antioxidants
Antioxidants can counteract the free radicals. Manganese appears to be helping to counteract free radicals in C. elegans, Srinivasan and her students explained, thereby minimizing the damage. “What we don’t know, at this time, is how manganese really works, whether the manganese is itself acting as an antioxidant or if it is enabling other antioxidants in C. elegans’s system to counter the free radicals,” Srinivasan said.

Srinivasan refuses to draw conclusions yet about what the research will mean to humans: “It’s too soon to tell. Right now we’re doing good science and good work, adding to the knowledge base on manganese. At the appropriate time, this will step up to mammalian research.” She stresses caution. For example, miners and welders are exposed to manganese during their work, she pointed out, “and some of them get Parkinsons-like symptoms, which may be related to the manganese toxicity. Of course, the big difference is that they are inhaling manganese particles, not ingesting it.”

Srinivasan said she refuses to extrapolate from the research or change her habits because of it. “One of the researchers at Johns Hopkins told me he has started taking manganese supplements. I’m not ready to do that. I just make certain I have a balanced diet, including whole grains, which is a good dietary source of manganese.”