The genes of Caenorhabditis elegans, a 1 millimeter-long, soil-dwelling roundworm or nematode, resemble those of people. Its genome - complete set of DNA with about 19,000 protein-coding genes - differs from ours in architecture but has some 60 percent protein conservation, where proteins expressed by the genes have similar shapes and functions. With a normal lifespan of just 20 days, C. elegans offer scientists at Novato-based Buck Institute for Research on Aging a keen glimpse of the aging process. A C. elegans worm has only 959 cells, each conveniently transparent when viewed through a microscope.
In 1993, Cynthia Kenyon, a biochemist and former faculty member at University of California, San Francisco with a Ph.D. from MIT, discovered that partially disabling the daf-2 gene which encodes the insulin-like growth factor receptor in C. elegans doubled its healthspan. It was a breakthrough. Like worms, humans have genes that control insulin-like growth factor. Since then she genetically tinkered further to give some worms a sixfold lifespan.
Scientists in laboratories at Buck continue to push C. elegans for answers to human aging, drawing on Kenyon's lead. Kathleen Dumas, post-doctoral research fellow for the past two years in Buck's Lithgow lab, also studies the worms. Dumas explores protein homeostasis in the worms. "With age, we have a breakdown in the normal maintenance of cells," Dumas said. "Protein folding can change with age." She is looking for genetic tools or drug molecules that can be used to shift protein misfolding. "We don't know that protein misfolding is causing aging. It could be the other way," that aging causes misfolding. "We see that it correlates. This is one of the bad things. If we can prevent protein misfolding, that could be one way to improve cellular functioning with age."
Cellular cleanup mechanisms and gene expression such as synthesizing protein change with age, Dumas said. Both processes relate to protein homeostasis inside cells. "Parkinson's and Alzheimer's are probably directly caused by aggregates of proteins that no longer do what they should," she said. "Proteins are the machines doing everything in our cells. If we have faulty parts or the wrong number of parts, those machines will break down. You get chaos - functional decline."