Insilico biomarkers and interventions in aging
Moskalev A1,2, Zhavoronkov A3, Aliper A3, Belikov AV2
1Institute of Biology of Komi Science Center of Ural Branch of Russian Academy of Sciences, Syktyvkar, 167982, Russia.
2Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia.
3Insilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA
A massive shift in the aging segment of the population will have major social and economic consequences around the world. One way to offset this increase is to expedite the development of geroprotectors, substances that slow aging and extend healthy lifespan, or healthspan. While over 200 geroprotectors are now reported in model organisms and some are in human use for specific disease indications, the path toward determining whether they affect aging in humans remains obscure.
GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. We shortlisted ten substances, all of which have lifespan-extending effects in animal models, and tested 6 of them for geroprotective effects in senescent human fibroblast cultures. PD-98059, a highly selective MEK1 inhibitor, showed both life-prolonging and rejuvenating effects. Natural compounds like N-acetyl-L-cysteine, Myricetin and Epigallocatechin gallate also improved several senescence-associated properties and were further investigated with pathway analysis. One of the major impediments in human aging research is the absence of actionable set of biomarkers that may be measured to track the effectiveness of therapeutic interventions. Using deep machine learning analysis we developed biological age model Aging.AI, which includes 41 input parameters of human blood. Using machine learning with 38 human health parameters, we arrived on a set of four predictors of chronological age, all of which reflect the functioning of the cardiovascular system.
Standardizing selection of geroprotectors with computational tools and the panels of human aging biomarkers will streamline discovery and analysis of new candidates, saving time and cost involved in translation to clinic.
1Institute of Biology of Komi Science Center of Ural Branch of Russian Academy of Sciences, Syktyvkar, 167982, Russia.
2Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia.
3Insilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA
A massive shift in the aging segment of the population will have major social and economic consequences around the world. One way to offset this increase is to expedite the development of geroprotectors, substances that slow aging and extend healthy lifespan, or healthspan. While over 200 geroprotectors are now reported in model organisms and some are in human use for specific disease indications, the path toward determining whether they affect aging in humans remains obscure.
GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. We shortlisted ten substances, all of which have lifespan-extending effects in animal models, and tested 6 of them for geroprotective effects in senescent human fibroblast cultures. PD-98059, a highly selective MEK1 inhibitor, showed both life-prolonging and rejuvenating effects. Natural compounds like N-acetyl-L-cysteine, Myricetin and Epigallocatechin gallate also improved several senescence-associated properties and were further investigated with pathway analysis. One of the major impediments in human aging research is the absence of actionable set of biomarkers that may be measured to track the effectiveness of therapeutic interventions. Using deep machine learning analysis we developed biological age model Aging.AI, which includes 41 input parameters of human blood. Using machine learning with 38 human health parameters, we arrived on a set of four predictors of chronological age, all of which reflect the functioning of the cardiovascular system.
Standardizing selection of geroprotectors with computational tools and the panels of human aging biomarkers will streamline discovery and analysis of new candidates, saving time and cost involved in translation to clinic.
