London, March 4
Scientists
propose the new in silico method for high throughput screening and ranking of
the possible geroprotector drugs to fight aging
Aging is one of the major challenges of
the modern society. The advances in biomedicine and healthcare systems have led
to the unprecedented long lives of the population after the retirement leading
to the increased burden on the economies. There is an urgent need to develop
and validate interventions with geroprotective properties to increase the
productive health spans of the working population and maintaining performance
and avoiding loss of function.
Experiments with animal models already
resulted in significant breakthroughs resulting in up to 1,000 percent
increases in lifespans. But extrapolating these advances to humans or other
mammals proved to be extremely challenging. Human live orders of magnitude
longer than the short-lived model organisms and there is no comprehensive set
of aging biomarkers, allowing to track the effects of the many drugs that may
extend lifespan. We are also different from other animals and the many drugs
that work on mice do not work on humans.
To address these challenges the
international team comprised of biogerontologists, geneticists, computer
scientists and biomathematicians proposed using a computer simulation and
laboratory validation approach using human cells and model organisms to predict
what drugs may help fight aging in humans.
The Human Genome Project and the
following revolution in sequencing and laboratory diagnostics resulted in the
vast data on genetic and epigenetic profiles of cells and tissues from people
of various ages. The proposed method uses this data to construct the cloud of
molecular signalling pathways involved in aging and longevity and evaluates the
effects of the very large number of drugs and drug combinations to simulate the
young state of the cells and tissues. Scientists hope that this method may be
used to find new drugs with aging-suppressive properties and predict the
activity of the drugs that are already on the market. Also, people respond to
the drugs differently and this method may be able to personalize the
geroprotective therapy to the individual patients and help the drug companies
conduct better clinical trials.
"There are thousands of compounds
with known molecular targets and some
are already used in the clinic. Due to high cost and the time it takes
to complete the experimental work, it may not be possible to test all of the
effects of these drugs even in mice. And the fact that the drug works in mice
does not guarantee the same effect in humans. There needs to be a better way to
predict the efficacy of the drug in humans.
We proposed a method for doing that in silico using the multiple sources
of data and we hope to validate this method in the very near future.",
said Alex Zhavoronkov, PhD, the director of the Biogerontology Research
Foundation in the UK. "Also, people are different, age at different rates
and respond to drugs differently. The proposed method may be used to predict
the personalized geroprotector regiments.", he added.
Many pharmaceutical companies already
expressed their interest in bringing aging research into clinical practice, but
the absence of the business models, accurate validation methods, and the
inability to classify aging as the curable disease are major impediments to
mainstream development of geroprotective drugs. In silico drug discovery may help
accelerate this process. The group plans to present the results of their
experimental work using this method at the Practical Applications of Aging
Research Symposium at MipTek 2014 in Basel, Switzerland attended by over 3,000
delegates from the pharmaceutical industry.
“The decreases in cost and increased
availability of genetic and epigenetic research as well as the breakthroughs in
computer technologies are already helping make better decisions in biomedicine.
The proposed method may take the in silico approach to drug discovery to the
next level. If they can validate it in the laboratory, and we are working on
that as we speak, this may revolutionize aging research”, said Anton Buzdin,
the director of the First Oncology Research and Advisory Center.
The paper describing the new approach to
screening and ranking of geroprotective drugs was published in the reputable
scientific journal Frontiers in Genetics.
Citation:
Zhavoronkov A, Buzdin AA, Garazha AV, Borissoff N and Moskalev AA (2014).
Signaling pathway cloud regulation for in silico screening and ranking of the
potential geroprotective drugs. Front. Genet. 5:49. doi:
10.3389/fgene.2014.00049 - See more at: http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00049/abstract#sthash.2qpLbytY.dpuf
The study is supported by the UMA
Foundation.
Media Contacts:
Victoria Zyulina
Tel.+79165937485
thewayinscience@gmail.com
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