November 20, 2009

JAX—West Helps Search for Compounds That Radically Extend Lifespan

In a novel approach to fighting disease and improving human health, RosScreening Inc., a subsidiary of Rostock Group, has enlisted the help of the Jackson Laboratory—West (JAX—West) to launch a mouse screening project that will test the ability of some 1,000 compounds to extend the lifespan of mice by at least 30%. If such compounds can be identified and are shown to have similar effects in humans, typical human life expectancies could be greatly extended, and human health could be significantly improved.

Although the scope of this project might seem immense, Dr. Alexey Ryazanov, Professor of Pharmacology at the Robert Wood Johnson Medical School and advisor for the project, says, "It's not as difficult as you might think. Today's technology makes this quite manageable. In fact, we are hoping to eventually test up to 100,000 compounds that cover virtually the entire spectrum of biologically relevant pharmacophore diversity space."

A $7 million initial phase of the project is already underway. In addition to testing the life-extending ability of the compounds, JAX will perform various clinical, pathological, and histological analyses to assess the compounds' effects on cancer and other age-associated diseases.

Why JAX?

When asked why JAX was chosen to oversee this project, Dr. Ryazanov responded: "JAX is highly respected and well known for its scientists and services. It has the highest concentration of experts - top scientists - working in the genetics field. JAX- West in Sacramento has the space, very high health status standards (so important in an aging study), breeding services, compound evaluation services, and pathology services - all in one place."

Dr. Ryazanov, advisor of the RosScreening Project: "Eventually tens of thousands of compounds covering the entire spectrum of biologically relevant pharmacophore diversity space will be tested."

Throughout the planning stages of this project, Dr. Ryazanov closely consulted with long-time and well-respected researcher on aging, JAX Professor David Harrison. Professor Harrison and his colleagues recently participated in the National Institute on Aging's Interventions Testing Program (ITP) and published their findings that rapamycin can extend the lifespan of mice (Harrison et al. 2009). The RosScreening Project differs from the ITP in several ways: The ITP project tests each compound on large cohorts of mice, conducts studies in triplicate, and uses committee-approved compounds. So far, it has tested only seven compounds, and the only one that has increased mouse lifespan – rapamycin – has done so by only about 10%. In contrast, the RosScreening Project is a large, rapid-paced, and high throughput screening project that will ultimately test thousands of compounds in relatively small groups of mice. Its goal is to find compounds that increase mouse lifespan by at least 30% – considerably more than rapamycin's effect. Professor Harrison believes this project has tremendous potential: "The focus is on large effects, increasing lifespan by 1/3 or more. Therefore the number of mice tested for each drug need not be very large, and large numbers of drugs can be tested. If there are unexpected mechanisms that cause conventional drugs to have large benefits on lifespan of the B6C3F1/J mouse, they will be found, and there is a good chance such benefits would mean basic mechanisms of aging were retarded. Because the risk of most chronic diseases (cancer, athrosclerosis, diabetes, arthritis, osteoporosis, Alzheimer's, Parkinson's, etc.) doubles with every eight- to nine-year increase in human age, a drug that retards aging greatly would prevent or postpone ALL those diseases. While a long shot, the project is valuable because it would have enormous health benefits if successful."

Reference

(Authors in bold are Jackson Laboratory scientists.)

Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. 2009. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392-5.