We need appropriate methodologies to study the pharmacology of aging in model species, if experimental findings with such systems are to be extrapolated to the treatment of human aging. While aging drug testing using the premier animal genetic systems, Drosophila melanogaster and Caenorhabditis elegans, has already started, the fundamental biological issues involved in such screening have not been systematically formulated. We have developed a number of bioassay to address this issue. In my laboratory, we not only screen compounds for their anti-aging properties but we also evaluate their impacts on known physiological confounds of anti-aging. These assays constitute a general testing protocol for anti-aging pharmacology. The results obtained from trials that adhere to this protocol should not be immediately extrapolated to humans, but they would help us to narrow the library of compounds that could be considered for further testing in vertebrate animal models, such as mice, and eventually humans. 

     We also suggest that adherence to the protocol we developed would improve the testing of candidate anti-aging treatments in mice and eventually humans as well. In the development of an anti-aging pharmacopia, it will be very important to monitor long-term side-effects of compounds, since these compounds are not primarily intended for the treatment of specific life-threatening diseases, and therefore may not have any value in conventional medicine. However, it is also possible that medications identified from their anti-aging benefits in model species may have value in the treatment of acute disease as well. In either event, we wish to emphasize that screening these drugs for their side-effects and other limitations will be of value throughout the process of drug research and development.

For a complete list of these bioassays, refer to: Jafari, M., Rose, MR. Rules for the use of model organisms in anti-aging pharmacology. Aging Cell. 2006. [Pubmed]

     Once an anti-aging compound is identified, we will examine its impact on various markers of the three components of the oxidative stress process; the generation of oxidants or free radicals, the antioxidant defenses, and the repair of oxidative damage. 

     In the case of Rhodiola rosea and Rosa damascena, we are in the process of evaluating their impact on the production of reactive oxygen species in vivo through aconitase activity, and in vitro from isolated mitochondria of herbal extract fed flies. To distinguish whether they act by direct interaction with ROS or through the modulation of mitochondrial function, we will measure mitochondrial oxygen consumption and enzyme activities of the respiratory chain and TCA cycle.