A valuable resource is being developed for scientists world wide who are attempting to unravel the mystery of aging, the single largest risk factor for human disease in developed countries. A unique research network, funded by the Larry L. Hillblom Foundation and led by scientists at the Buck Institute, will screen as many as 120,000 chemical compounds over the next four years to discover which ones impact lifespan in four research models – yeast, nematode worms, fruit flies and mice. Results of the work, unprecedented in terms of scale for chemical screening, will be made public.
The research highlights a new area of science: the chemical biology of aging. Using high-tech methodology, the network aims to identify potential “needles in a haystack” of chemicals, giving age researchers new starting points for experiments based on compounds that have never been considered as candidates for lifespan extension.
“We believe this is the first true chemical exploration of lifespan extension across multiple species,” said Gordon Lithgow, PhD, Buck Institute faculty member and project leader. “Our aim is to discover and develop novel compounds; at the very least we hope to identify 100 chemically distinct compounds that slow aging, opening up new avenues to treat, prevent or postpone age-related conditions such as Alzheimer’s disease, cancer, arthritis, and diabetes, among others.” A number of Buck Institute faculty members will be initial members of the network, including Robert E. Hughes, PhD; Simon Melov, PhD; and Pankaj Kapahi, PhD. Laura Dugan, MD, Professor of Geriatric Medicine at the University of California, San Diego School of Medicine will also be included in the research project.
The Hillblom Chemical Biology of Aging Network will conduct its research in the style of an inverted pyramid. The largest number of compounds will be screened, in many cases via the use of robotics and other high-tech devices, in the simplest organisms – budding yeast (in the Hughes lab) and nematode worms (in the Lithgow lab). Chemicals that extend lifespan in those species will go on to be tested in the fruit fly (in the Kapahi lab). Chemicals that cause all three species to live longer will be looked at in mice, to see if there is a reversal of the molecular characteristics of aging (in the Melov and Dugan labs). The evolutionary distance between yeast and worms predicts that compounds active in both these species are likely to be relevant to mice and humans. Mice have the strongest similarity to humans of all of the animal models currently used in age research, sharing about 85 per cent of their genetic make up with Homo sapiens.