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Summary:
- An international group of expert scientists led by Insilico Medicine published a research paper, "In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state" in one of the highest-impact journals in the field, "Aging"
- The paper presents a novel way to screen for compounds that demonstrate geroprotection by mimicking the young healthy state in tissue samples from elderly subjects using computational approaches and in vitro validation
- The top geroprotector, in terms of performance in both enhancing viability and rejuvenation was PD-98059, a highly selective inhibitor of MEK1 and the MAP kinase cascade. Natural compounds predicted to have excellent geroprotective efficacy and safety in humans include N-acetyl-L-cysteine (NAC), Myricetin and Epigallocatechin gallate (EGCG)
- Scientists used ensembles of deep neural networks to predict the safety of the compounds
- Reference: Aliper, et al (2016) "In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state" Aging (Albany NY), DOI: 10.18632/aging.101047 , http://www.aging-us.com/article/MHpmpbTNuNqLnCN9g/text#fulltext
Friday, October 7, Baltimore, MD - Insilico Medicine, Inc. today announced the publication of a research paper describing the applications of its human signaling pathway-centric GeroScope platform for scoring human tissue-specific geroprotective properties of compounds implicated in the aging of model organisms. GeroScope utilizes large human gene expression databases to analyze changes in tissue samples from healthy young compared with old human subjects at the level of signaling pathways implicated in aging and longevity. This enables the identification of compounds with known transcriptional response profiles that may be able to mimic the young healthy state in old human tissues. In collaboration with Life Extension Foundation Buyer's Club, Inc., a trailblazer in the dietary supplement industry with a focus on health and wellness, authors analyzed the top scoring naturally-occurring compounds to predict the possible pathway-level synergy of combinations.
"Life Extension Foundation Buyer's Club is a science-based nutritional supplement company recognized for their cutting-edge products and information. We are happy to collaborate with Life Extension Foundation Buyer's Club and their deep passion for health and wellness. Together we will make a major impact on the identification of natural compounds with critical health, wellness, and longevity properties," said Alex Zhavoronkov, PhD, CEO of Insilico Medicine, Inc. and the CSO of the Biogerontology Research Foundation (UK).
The study initiated with 70 compounds that already had been implicated in extension of life span in animal models (Geroprotectors.Org) for which transcriptional response data in human cell lines was available. The compounds were scored for their ability to mimic the young healthy state in old tissues and the list of compounds was narrowed to just a few candidates that were ordered and tested in human senescent fibroblasts.
"We are excited to have these results published, since they served as an excellent platform for follow up studies we have underway. Over the past year we made considerable progress in applying deep learning to geroprotector discovery and development of comprehensive biomarkers of aging and reconfirmed some of the findings in this paper using other methods," said Alex Aliper, president of Insilico Medicine and the lead author on the paper.
To predict the possible side effects of the compounds the scientists applied the available transcriptional response data to ensembles of the deep neural networks trained on tens of thousands of samples. While not without caveats, this approach may serve as the proof of concept for evaluating the possible adverse effects of compounds that have not yet been tested in humans.
"We at Life Extension Foundation Buyer's Club are focused on identifying natural products with critical health and wellness properties. Our collaboration with Insilico Medicine will enable us to apply artificial intelligence, sophisticated biologically-inspired algorithms and our knowledge of dietary supplements to the discovery and development of unique science-based products. This paper represents an example of merging artificial intelligence with natural product knowledge to produce leading-edge scientific results," said Andrew G. Swick, PhD, senior vice president of scientific affairs, discovery research and product development for Life Extension.
"There has been much progress in biogerontology in the recent years and while working with model organisms, we need new methods for estimating the potential utility for humans. Insilico Medicine is clearly leading the way in this regard. In this paper we demonstrated proof of concept, where geroprotective efficacy is predicted and then validated experimentally in human senescent cells," said Alexey Moskalev, PhD, DSc, professor of the Russian Academy of Sciences, adjunct professor of the George Mason University and advisor to Insilico Medicine.
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Journal reference: Aliper, et al (2016) "In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state" Aging (Albany NY), DOI: 10.18632/aging.101047 http://www.aging-us.com/article/MHpmpbTNuNqLnCN9g/text#fulltext
About Life Extension
A trailblazer in the $35 billion U.S. dietary supplement industry for the past 36 years, Life Extension Foundation Buyer's Club's mission is providing cutting-edge information and dietary supplements to facilitate healthy longevity. Life Extension Foundation Buyer's Club, Inc. ("Life Extension") offers a full-range of premium-quality dietary supplements as well as unique, scientifically-supported formulas. The company's products are developed based on scientific studies from peer-reviewed medical journals and are consistently updated as new information occurs. To learn more about Life Extension Foundation Buyer's Club, visit http://www.lifeextension.com/
About Insilico Medicine
Insilico Medicine, Inc. is a bioinformatics company located at the Emerging Technology Centers at the Johns Hopkins University Eastern campus in Baltimore with R&D resources in Belgium, Russia and Poland hiring talent through hackathons and competitions. It utilizes advances in genomics, big data analysis and deep learning for in silico drug discovery and drug repurposing for aging and age-related diseases. The company pursues internal drug discovery programs in cancer, Parkinson's, Alzheimer's, sarcopenia and geroprotector discovery. Through its Pharma.AI division the company provides advanced machine learning services to biotechnology, pharmaceutical and skin care companies. Brief company video: https://www.youtube.com/watch?v=l62jlwgL3v8