Researchers at the Laboratory of Genetics of Aging and Longevity of the Moscow Institute of Physics and Technology together with specialists from Insilico Medicine developed an algorithm for searching for geroprotectors, therapeutics that prolongs the life span of humans and tested 10 substances found with the new algorithm. The work was commissioned by the Center for Bio-gerontology and Regenerative Medicine and published in the American journal Aging. The new algorithm GeroScope was developed on the basis of the previously developed algorithm Oncofinder, which analyzed the values of molecular pathways activation via comparing gene expression in cancer and non-cancer cells.
The new algorithm offers an opportunity to compare the changes in the cells of young and aged patients and to search for therapeutics that compensate for such changes with minimal side effects. To develop the algorithm the researchers analyzed transcriptomics data from cell samples from young (ages 15-30) and aged (over 60) donors. The researchers used the data obtained in computer modeling to build molecular pathways associated with aging.
In the course of the experiment the 10 substances under review that had been selected at the computed modeling stage yielded different results. For example, NDGA produced no rejuvenation effect and reduced the life span, Myricetin had a light rejuvenation effect but greatly reduced the life span, EGCG had a strong rejuvenation effect but radically reduced the life span. NAC produced a light rejuvenation effect but radically extended the life span, PD-98059 yielded strong effects both in term of rejuvenation and life span extension.
For several substances the forecasts produced by computer modeling were confirmed in cell cultures of human fibroblasts: PP-98059, NAC, Myricetin и EGCG. Some of these substances are already on sale as bioactive food supplements.
Testing the selected substances revealed a high correlation of the algorithm’s work with experimental data. In the future, GeroScope will be used to search for unknown geroprotective substances.
Maria Buras