Wednesday, December 7, 2016

The AI that could uncover the secret of eternal youth

Scientists have revealed a new plan to find the key to eternal youth – and artificial intelligence will be leading the way.

Using computer simulations to screen hundreds of compounds, researchers have developed a tool that can identify geroprotectors, the substances responsible for extending healthy life.

GeroScope can compare changes in the cells of young and old patients and search for the drugs that counteract the processes.

The project is led by scientists from Moscow Institute of Physics and Technology and Insilico Medicine Inc, commissioned by the Center for Biogerontology and Regenerative Medicine.

According to the researchers, using computer modelling techniques can help to cut down time and cost in the development of age-combating drugs.

‘The aging of population is a global problem,’ said Alexey Moskalev, a corresponding member of the RAS and head of the Laboratory of Genetics of Aging and Longevity.

‘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 researchers previously studied cancer-related processes using the Oncofinder, an algorithm designed to compare cancerous and healthy cells, along with tissue samples.

They’ve now used a similar approach for GeroScope.

The team first analyzed transcriptomic data – that which is read from DNA and transcribed into RNA – in tissue samples from donors aged 15-30 years old, and donors over the age of 60.

This was used for advanced computer modelling to identify and re-construct the molecular pathways associated with aging.

These are the reaction sequences that lead to changes in a cell.

The tool was able to model molecular pathways and analyze the cell reaction to various substances, choosing 70 compounds from a database of geroprotective drugs previously published by the team.

Then, they used the new algorithm to identify 10 substances that could have life-extending potential.

The researchers then conducted laboratory experiments on the ten substances, using stem cell lines of human fibroblasts (connective tissue cells) to study two effects: cell ‘rejuvenation’ and survival.

First, they took measurements of the cells, including size, shape, and complexity of the internal structure.

The cells were then mixed with a substance and growth medium, and held in this state for 6, 12, and 18 days.

After this time had passed, the researchers measured the same features as before, along with levels of beta-galactosidase, a marker of aging.

The experiments revealed the 10 substances had different results across the human cells.

A substance called NDGA was found to have no effect on rejuvenation, but can decrease short and long-term survival.

While NAC has a mild rejuvenating effect, it dramatically decreases survival.

Myricetin, they found, has a mild rejuvenating effect, and EGCG has a strong rejuvenating effect.

But, a substance called PD-98059 was found to have a very strong rejuvenating effect, and increases both short and long-term survival.

In cell cultures of the human fibroblasts, the predictions made by the computer model were confirmed across the latter four substances.

According to the researchers, some of these are already sold as dietary supplements.

Future with is now needed to determine the effects of these compounds, and provide insight on the combinations that could be used to maximize the benefits while minimizing any side effects.

‘For computer modelling this is a very good result,’ said Alex Zhavoronkov Ph.D., head of the Laboratory of Regenerative Medicine at the D. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology, and Immunology, an adjunct professor at MIPT, and head of Insilico Medicine Inc.
‘In the pharmaceutical industry, 92 percent 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 aging.’ 


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