Successful Use Of Drugs To Extend Lifespan

In a collaborative effort, scientists have for the first time successfully increased normal life span in the nematode worm C. elegans through the use of drugs that augment the organism’s natural antioxidant systems. As reported in the September 1, 2000 issue of Science, it appears that oxidative stress is a major determinant of life span and that it can be counteracted by pharmacological intervention.

The findings are the result of a research collaboration, initiated by Dr. Simon Melov of the Buck Institute (Novato, CA), including Dr. Gordon Lithgow and colleagues of the University of Manchester (Manchester, UK), Dr. Doug Wallace of Emory University (Atlanta, GA) and Drs. Susan Doctrow and Bernard Malfroy of Eukarion Inc., (Bedford, MA).

The experiments involved groups of adult nematodes that were either untreated or treated with synthetic catalytic scavengers, or SCSs. These drugs are synthetic versions of superoxide dismutase and catalase, naturally occurring enzymes involved in the control of oxidative stress. The team of researchers found that treatment of adult wild-type nematodes with synthetic superoxide dismutase/catalase mimetics had mean life spans that were on average, approximately 50% longer than the untreated nematodes.

Furthermore, in a mutant nematode strain with a shortened life span linked to oxidative stress, an early death was prevented and life span normalized through treatment with the drugs. Results suggest that endogenous oxidative stress is a major determinant of the rate of aging.

Nematodes have been used for many years to study biological processes relevant to other species including humans.

“These results are the first real indication we have had that aging is a condition that can be treated through appropriate drug therapy,” said Dr. Melov, a founding faculty member of the Buck Institute, who initiated the pilot studies. “Further studies on higher organisms in the near future will allow us to answer whether or not we have to reconsider aging as an inevitability.”

“We have been working on our proprietary synthetic catalytic scavenger (SCS) compounds for several years,” said Dr. Bernard Malfroy, chief executive of Eukarion. “To date, they have been successfully used in models of neurodegenerative, cardiovascular, autoimmune and inflammatory diseases. This work on nematode life span further strengthens our belief that SCSs have tremendous potential as therapeutics. Our priority now is to move these compounds toward clinical trials.”

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