Scientists in Moscow have developed a ‘GeroScope’ algorithm, a means of identifying geroprotectors – substances that extend healthy life.
The computer modelling technique is intended to reduce the time and cost in developing new drugs and interventions intended to combat ageing, a complex, multifactorial biological process affecting every cell in the human body.
A core of scientists involved in Russia’s growing ageing research community were involved in the project: a team from Moscow Institute of Physics and Technology (MIPT), in collaboration with Insilico Medicine Inc, were commissioned by Moscow’s Center for Biogerontology and Regenerative Medicine to develop the algorithm. Hundreds of compounds were screened for geroprotective activity using computer simulations, and laboratory experiments were conducted on the 10 substances that were identified using this algorithm.
Alexey Moskalev, member of the Russian Academy of Sciences and head of MIPT’s Laboratory of Genetics of Aging and Longevity, says: “The aging of the population is a global problem. Developing effective approaches for creating geroprotectors and validating them for use in the human body is one of the most important challenges for biomedicine. We have proposed a possible approach that brings us one step closer to solving this problem.”
The GeroScope is able to compare changes in the cells of young and old patients by modelling molecular pathways and analysing cell reactions to various substances, then searching for drugs with minimal side effects that compensate for these changes.
To experimentally verify the algorithm, the scientists took stem cell lines of human fibroblasts (connective tissue cells) and studied the effects of the test substances on cell rejuvenation and cell survival. The predictions made by the computer model were confirmed in the cell cultures for several substances: PP-98059, NAC, Myricetin and EGCG.
“For computer modelling this is a very good result,” said Alex Zhavoronkov Ph.D., head of the Laboratory of Regenerative Medicine at Moscow’s D. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology, and Immunology, an adjunct professor at MIPT, and head of Insilico Medicine Inc. (Emerging Technology Centers located at the Johns Hopkins University at Eastern Campus).
“In the pharmaceutical industry, 92 per cent of drugs that are tested on animals fail during clinical trials in humans. The ability to simulate biological effects with such a high level of accuracy in silico is a real breakthrough. PD-98059 and NAC proved to be the strongest geroprotectors. We hope that some of these drugs will soon be tested on people using biologically-relevant biomarkers of ageing.”
It is expected the GeroScope will later be used to search for unknown substances with geroprotective effects as well as for compounds that may be used to treat a variety of age-related conditions.
Featured image: An abstraction of ageing (Credit: MIPT’s Press Office)