Drug Commonly Used To Treat Bipolar Disorder Dramatically Increases Lifespan In Worms

Lithium has been used to treat mood affective disorders, including bipolar disease for decades. While the drug has been shown to protect neurons, the underlying mechanism of its therapeutic action is not understood. In humans, lithium's therapeutic range is very limited and the drug has serious side effects. The research provides a novel genetic approach to understanding how lithium works and highlights the utility of using the nematode C. elegans as a research subject in the field of "pharmacogenetics". Pharmocogenetics involves the study of genetic factors that influence an organism's reaction to a drug.

In the study, scientists discovered that longevity was increased in the worms when the lithium "turned down" the activity of a gene that modulates the basic structure of chromosomes. Results of the Buck Institute study, led by faculty member Gordon J. Lithgow, PhD, are currently published online in the Journal of Biological Chemistry.

Lithgow believes that lithium impacts many genes. "Understanding the genetic impact of lithium may allow us to engineer a therapy that has the same lifespan extending benefits," said Lithgow. "One of the larger questions is whether the lifespan extending benefits of the drug are directly related to the fact that lithium protects neurons." The process of normal aging in humans is intrinsically linked to the onset of neurodegenerative disease.

However, the cellular changes and events due to aging that impact neurodegeneration are not yet understood said Lithgow. Studies involving compounds such as lithium could provide breakthroughs in the attempt to understand the biomedical link between aging and disease. Lithgow and his lab are now surveying tens of thousands of compounds for affects on aging.

The study highlights the efficacy of using C. elegans as a new way of studying drug toxicity and genetic impacts of compounds currently in drug development or already in use in humans. "The use of simple model organisms with well developed genetic tools can speed the identification of molecular targets," said Lithgow. "This could facilitate the development of improved therapies for diseases."

Others involved in the study include Simon Melov and Maithili C. Vantipalli, also of the Buck Institute; Gawain McColl, the lead author, formerly of the Buck Institute, now at the Mental Health Research Institute of Victoria, Australia; along with David W. Killilea of Children's Hospital Oakland Research Institute, Oakland, CA and Alan E. Hubbard, University of California, Berkeley.

G.M was supported by the American Federation for Aging Research. S.M was supported by the Ellison Medical Research Foundation, and NIH AG24385 and AG18679. G.J.L is supported by NIH AG21069, AG22868, NS050789-01, the Ellison Medical Research Foundation, the Glenn Foundation for Medical Research and the Herbert Simon Family Medical Foundation. Gene expression studies were facilitated by a Nathan Shock award P30AG025708. All other nematode strains were obtained from the Caenorhabditis Genetics Center, funded by the National Institutes of Health National Center for Research Resources.