by Buck Institute

Unprecedented Screening of Up to 120,000 Chemical Compounds for Lifespan Extension to Begin

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.

The research is being organized as a formal network, as opposed to a number of collaborative agreements, given that the work cannot be done in a parallel fashion and the success of one group is dependent on the success of others in the network.

“The Hillblom Foundation is dedicated to supporting scientific studies of healthy aging and the treatment of diseases related to aging. The Buck Institute Network Research Project is a major step in this direction,” said Peter Donnici, President of the Larry L Hillblom Foundation. “Based on the level of expertise of those involved in this research, we believe identifying the ‘Hillblom List’ of 100 distinct life-extending chemical compounds is a realistic goal.” Donnici added, “The fact that the results of this work will be made public will provide a boon to scientists world wide.

The grant provides $1.7 million over four years. “The unique combination of interests, expertise and technologies puts the Buck Institute, perhaps exclusively, in a position to achieve this ambitious goal rapidly and effectively,” said Dale Bredesen, MD, Director and Chief Executive Officer of the Buck Institute. “Many consider studies of the chemical biology of aging to be the next ‘frontier’ in age research,” added Bredesen. “We are grateful to the Larry L. Hillblom Foundation for supporting this effort.”

The Buck Institute is the only freestanding institute in the United States that is devoted solely to basic research on aging and age-associated disease. The Institute is an independent nonprofit organization dedicated to extending the healthspan, the healthy years of each individual’s life.  The National Institute of Aging designated the Buck a Nathan Shock Center of Excellence in the Biology of Aging one of just five centers in the country.  Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating conditions such as Alzheimer’s and Parkinson’s disease, cancer, arthritis and stroke.  Collaborative research at the Institute is supported by new developments in genomics, proteomics and bioinformatics technology.

Science is showing that while chronological aging is inevitable, biological aging is malleable. There's a part of it that you can fight, and we are getting closer and closer to winning that fight.

Eric Verdin, MD, Buck Institute President and CEO

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