The Classification and Screening of Geroprotector Drug Candidates

One faction in the aging research community defines drugs that modestly slow aging as "geroprotectors," and maintains an online database of studies and results for such drug candidates. These drug candidates generally work through alterations to metabolism that either slow the pace of accumulated cell and tissue damage, or make older individuals modestly more resistant to the consequences of that damage. These are all marginal effects - don't look for rejuvenation and radical life extension in this part of the field. That can only occur through comprehensive repair of the molecular damage that causes aging. Geroprotectors are perhaps best represented at this time by calorie restriction mimetics, replicating some fraction of the beneficial response to a lower calorie intake, and by compounds that boost autophagy, increasing cellular repair and maintenance.

Aging causes disease progress and a gradual decline in physical and mental function. Because of the rapid aging of the population, the risk of economic collapse in developed countries is increasing. Therefore, anti-aging and disease prevention has become a high priority science challenge. Although geroprotector discovery is a popular biomedical trend and more than 200 compounds can slow aging and increase the lifespan of animal models, there are still no geroprotectors on the market. The reasons may be related to the lack of a unified concept of aging mechanisms, the problem of translation of geroprotectors studies results from model organisms to humans, low level of interest from big pharma since aging has no status as a disease.

But one of the main obstacles, in our opinion, is the lack of a concept of geroprotector accepted by the scientific community. Such concept as a system of criteria for geroprotector identification and classification can form the basis for an analytical model of geroprotectors, help consolidate the efforts of various research initiatives in this area and compare their results. This model can serve as a platform for formulating and solving a variety of tasks, from a selection of the most promising and efficient existing candidate geroprotectors to possible constructing of a model geroprotector that can be searched in the libraries of compounds or synthesized purposefully.

The most significant main rule for geroprotectors is evidently the ability to increase lifespan. Candidate geroprotectors should ameliorate molecular, cellular, and physiological biomarkers to a younger state or slow the progression of age-related change in these markers. The therapeutic lifespan extending dose of a geroprotector should be several orders of magnitude less than the toxic dose. Potential geroprotectors should improve health-related quality of life: physical, mental, emotional, and social functioning of the treated person. The target or mechanism of action of the geroprotector should be evolutionarily conserved. Reproducibility of geroprotective effects on different model organisms increases the possibility of effects will also be discovered in humans, even in the absence of a known conserved target. Candidate geroprotectors should be able to delay the progress of one or several age-associated disorders. Potential geroprotectors should increase the organism's resistance to unfavorable environmental factors.

The compliance of a substance with at least the majority of these criteria allows the claim that we are dealing with a candidate geroprotector. With the help of modern mathematical tools for data analysis and decision-making, such a system would facilitate formulating and solving a number of important scientific and applied problems, the most significant of which is the selection of geroprotectors with the largest and most reliable effect on life expectancy.

Link: http://www.aginganddisease.org/article/2017/2152-5250/147577

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