Geroprotectors: A Unified Concept and Screening Approaches

Abstract

Although the geroprotectors discovery is a new biomedicine trend and more than 200 compounds can slow aging and increase the lifespan of the model organism, there are still no geroprotectors on the market. The reasons may be partly related to the lack of a unified concept of geroprotector, accepted by the scientific community. Such concept as a system of criteria for geroprotector identification and classification can form a basis for an analytical model of anti-aging drugs, help to consolidate the efforts of various research initiatives in this area and compare their results. Here, we review the existing classification and characteristics of geroprotectors based on their effect on the survival of a group of individuals or pharmaceutics classes, according to the proposed mechanism of their geroprotective action or theories of aging. After discussing advantages and disadvantages of these approaches, we offer a new concept based on the maintenance of homeostatic capacity because aging can be considered as exponential shrinkage of homeostatic capacity leading to the onset of age-related diseases and death. Besides, we review the most promising current screening approaches to finding new geroprotectors. Establishing the classification of existing geroprotectors based on physiology and current understanding of the nature of aging is essential for putting the existing knowledge into a single system. This system could be useful to formulate standards for finding and creating new geroprotectors. Standardization, in turn, would allow easier comparison and combination of experimental data obtained by different research groups.

Is anti-ageing drug discovery becoming a reality?

“…We have theorized that the classification of geroprotectors be based on the concept of homeostasis [15] or, more accurately homeodynamics. These can be separated into four groups:…”

Studying the geroprotective effects of inhibitors suppressing aging -associated signaling cascades in model organisms

“…To date there is an opportunity to select the pharmacological inhibitors for pro-aging factors and also it is possible to sort out the inhibitors which activate expression of pro-longevity genes by suppression of its negative regulators. So-called «target approach» is probably the syntheses of the genetics of aging and longevity, modern drug design and advances in translational medicine (using model organisms) [37].…”

“…The pharmacological agents that decrease the rate of aging and extend lifespan are called geroprotectors [36][37][38]. The term «geroprotector» (literally «protecting from aging») was first coined by the Nobel Prize laureate Ilya Mechnikov, an outstanding Russian and French scientist, in 1910 [35], but those times the concept had not been widely used before enough empirical data was accumulated.…”

“…Recently, the system of criteria for geroprotector identification and classification were proposed [37,38]. The main criteria are (1) the ability to prolong life, in addition, a potential geroprotector should (2) return the biomarkers of aging to the state characteristic of a young organism; (3) the dose providing effective use must be fundamentally lower than the toxic dose with (4) minimal side effects at therapeutic dosage, and, finally, (5) the quality of life in patients treating with geroprotectors should increase, and the physical, mental, emotional state should improve.…”

“…The products of genes that affect longevity and aging represent potential targets for pharmacological intervention [9,37]. The candidate geroprotectors may be selected from a libraries of natural and synthetic compounds or discovered by computerassisted molecular design approaches [22].…”