Suzanne Angeli, a postdoctoral researcher in Gordon Lithgow’s lab at Novato’s Buck Institute for Research on Aging for five years, studies Parkinson’s disease in the tiny C. elegans worm that stands only about 1 millimeter tall and thrives on rotting fruit, but offers far-reaching views of many aspects of aging biology.
“The worms have a complete nervous system,” Angeli said. “If you put a pathogenic protein” from Parkinson’s disease “in the worms’ neurons, they start to degenerate” in ways similar to human patients with the disease.
She sought clues on how environmental risk factors — such as exposure to toxins, herbicides, pesticides, heavy metals — might induce or aggravate Parkinson’s. In particular, Angeli examined the effect of manganese in worms with Parkinson’s proteins.
Manganese “has been shown in people to affect the disease progression,” she said, correlated with higher risk. Some manganese miners develop a nerve disorder called manganism apparently due to prolonged exposure to the metal. “It’s very similar to Parkinson’s,” Angeli said. “It affects the same area of the brain.”
Some pesticides contain manganese. “You can breathe it,” she said.
“Manganese is toxic,” Angeli found. “It does affect aging worms. It shortens their lifespan” from 20 to 50 percent at high doses.
Manganese also increases protein aggregation — another symptom of Parkinson’s — in C. elegans. “We see the worms get very sick,” she said. “Manganese can initiate a cascade of protein misfolding,” a characteristic of Parkinson’s.
Manganese causes malfunctioning of mitochondria, the energy source of cells, Angeli said. She seeks drugs that might ameliorate symptoms of manganese toxicity.
“It’s fun,” she said. The idea that her work might help extend people’s lives is “hugely motivating.”
Now she is looking at epigenetics, modifications in gene expression due to a marker placed on top of DNA. “It changes how DNA is expressed,” Angeli said, possibly increasing resistance to Parkinson’s and other diseases. “It’s not changing the genetic code.” The genetic code of C. elegans is very well understood by scientists.
Different environments can affect gene expression in the worm. “This is a new project,” she said. Findings from research with C. elegans can be transferred to studies on laboratory mice, then potentially to humans.