Anti-aging Drugs: From Basic Research to Clinical Practice
CHAPTER 4: Testing of Geroprotectors in Experiments on Cell Cultures: Pros and Cons
Published:18 Jan 2017
Special Collection: 2017 ebook collectionSeries: Drug Discovery
Alexander N. Khokhlov, Galina V. Morgunova, 2017. "Testing of Geroprotectors in Experiments on Cell Cultures: Pros and Cons", Anti-aging Drugs: From Basic Research to Clinical Practice, Alexander M Vaiserman
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The chapter is a critical review of various approaches to testing of geroprotectors (anti-aging compounds or physical factors) in experiments on cultured cells. The most popular cytogerontological models are reviewed with a focus on general gerontological definitions (aging, cell senescence, biomarkers of aging, aging and non-aging organisms, geroprotectors, age-related diseases, etc.). Among the model systems are the Hayflick model, the stationary phase aging model, and the cell kinetics model. Most attention has been paid to methodological aspects of the testing of geroprotectors with these models. Questions arising when constructing survival curves for cultured cells in the “stationary phase aging” model are analyzed. In particular, consideration is given to some problems encountered when using the most widespread molecular probes designed for live/dead cell viability assays. A note is made that the evaluation of colony-forming efficiency, though optimal for cell viability assessment, is unfortunately not applicable to postmitotic or very slowly propagating cells. Some questions regarding the interpretation of data obtained in such studies in application to humans are also considered. Popular approaches to choosing biomarkers of cell aging/senescence are briefly reviewed. It is assumed that the least number of problems associated with interpreting the results of testing potential geroprotectors in cytogerontological experiments arise when such studies are performed using normal human cells in the model of stationary phase aging, which is based on the concept of cell proliferation restriction as the main cause of accumulation of macromolecular lesions in cells of multicellular organisms with age. However, in the authors' opinion, even this approach will not give the final answer to the question of whether or not the studied factor is a geroprotector. Answering this question will inevitably require both “classic” gerontological experiments in animals and clinical trials.