Historic BAIT Project Underway at the Buck Institute

BAIT - Chris Zambataro
Research associate Chris Zambataro reviews a 3-D image of a mouse skeleton.

BAIT – the Buck Aging Intervention Testing project – is arguably the most exciting and significant venture undertaken in the Institute’s history.  It is poised to be a paradigm shifter in the field of aging research and to provide a desperately needed roadmap for moving promising therapies into human clinical trials. 

“For a long time, we as an aging research community really have been focused on the survival curve,” points out BAIT project director Simon Melov, PhD. The goal had been to find treatments or genetic mutations that increase lifespan in mice, pushing the survival curve to the right. However, “there have been precious few examples of understanding what the functional consequences of pushing the survival curve are,” says Melov. “It’s not necessarily a given that if you increase lifespan you will increase healthspan.”

“We want to move therapies into the clinic; knowing how treatments impact specific functional parameters in the mice could give us a way to guide clinical trials in humans.”  This is the vital information that’s been lacking.”
 ‐Brian Kennedy, PhD, Buck Institute President and CEO

With BAIT, Melov and other Buck faculty are building a resource for tracking how mice age, both in response to drug treatment and under normal physiological conditions.  It’s a “big data” project that is yielding terabytes of information on physiological markers of health including cardiac function, metabolism, bone density, body composition, activity and blood pressure, among others.  “We are creating the gold standard for looking at variability in aging in mice,” says Melov. 

The initial BAIT project involves 770 genetically identical mice that entered the study at 20 months of age (roughly equivalent to a 60-year-old human).  One subset is aging normally;  other subsets are being individually treated with four drugs that have already been shown to increase lifespan in simple animals such as worms and flies.  Halfway in, the project is already yielding valuable information. 

“Data from BAIT will provide us with numerous jumping-off points to push the research forward,” said Brian Kennedy, PhD, Buck President and CEO, who committed institutional support for the initial project. “We want to move therapies into the clinic; knowing how treatments impact specific functional parameters in the mice could give us a way to guide clinical trials in humans.”  This is the vital information that’s been lacking.” 

Melov describes BAIT as the Buck’s “Human Genome Project”– one that is big, bold, costly, risky and difficult, with the potential for enormous payoff.  It is a perfect manifestation of the Buck’s collaborative research environment. Faculty Gordon Lithgow, Julie Andersen and Pankaj Kapahi helped Melov choose the four drugs currently being tested. Other faculty anxiously await data that that can further their own specific age-related research.

BAIT is already the largest study in the world looking at functional aging in mice. This comprehensive and unique monitoring is made possible by the resources at the Buck -  because the instruments are all available in the same animal facility, the mice can be tested under one roof with little stress or disturbance. “Other researchers have attempted this type of project, but the mice had to be transported to different facilities,” said Melov. “It’s a major factor that negatively impacts results and it’s one that we bypass.”

And now that the pipeline is established, there is no reason not to scale up even further. Melov thinks that, given the resources, BAIT could handle up to 50 or 60 compounds, providing a next-generation resource for drug development. As new treatments are tested, their effects on health can be compared not only to control animals, but also to the growing database of previously screened drugs. 

In addition to Buck monies, funding for the initial project comes from the Glenn Foundation for Medical Research and the National Institutes of Health. Additional monies are needed to move the project forward. “We are actively seeking support to expand BAIT,” said Kennedy. “This is a perfect opportunity for donors to get directly involved in projects that have measurable results and are primed to make a major impact on our efforts to extend healthspan.”  Anyone interested in more information about funding BAIT should contact Todd Plummer at 415-209-2067/tplummer@buckinstitute.org.  

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