A comprehensive analysis of the genetic and epigenetic mechanisms by an
international group of scientists demonstrated that the majority of the
genes, as well as genetic and epigenetic mechanisms that are involved in
regulation of longevity, are highly interconnected and related to
stress response.
Since the dawn of civilization people were searching for clues to
longevity and trying to extend human lifespan. But only in the past two
decades with the advances in genetic sequencing, epigenetic analysis,
and increased government investments the area experienced rapid
expansion in the knowledge base, allowing scientists to develop
comprehensive models and theories of aging. And while there is still
much disagreement among scientists, the evolutionary theories are
dominating the field. These theories predicted existence of certain
genes that provide selective advantage early in life with adverse
effects on lifespan later in life or longevity insurance genes. Indeed,
the study of human and animal genetics is gradually identifying new
genes that increase lifespan when overexpressed or mutated --
gerontogenes. Furthermore, genetic and epigenetic mechanisms are being
identified that have positive effects on longevity.
"The study of the effects of mutations and epimutations on life
expectancy and the aging rate expands the range of potential
pharmacological and genoteraputic targets, as well as biomarkers of
treatment of aging-dependent pathologies," said professor Alexey
Moskalev, PhD, DSc, head of the laboratories for aging research at the
Institute of Biology of the Russian Academy of Sciences and at the
Moscow Institute of Physics and Technology.
The international
group of scientists performed a comprehensive analysis of the genetic
and epigenetic mechanisms and demonstrated that the majority of the
genes, as well as genetic and epigenetic mechanisms that are involved in
regulation of longevity, are highly interconnected and related to
stress response. Also, for the first time, the group performed a
comprehensive analysis of government research grants related to the
genes involved in aging. One of the tools that may help understand the
direction of scientific research that is still unpublished are research
grant abstracts. To better understand the general trends in aging
genetics, the funding and citation information for the longevity genes
was collected using the International Aging Research Portfolio (IARP)
system as well as the NCBI PubMed system.
Grants analysis led to interesting conclusions. The science of aging
genetics is a comparatively new field. P53 was discovered in 1979 and
implicated in aging in 1987. On average, genes in Table 2 were
discovered 21 years ago and it took 9.7 years between the first citation
and the first citation with "aging." The approximate amount of funding
spent on genes related to aging is at over $8.5 billion with over
195,000 citations with the most funding spent on genes involved in
stress response. On average approximately 7.4% of the funding was spent
on projects with "aging" in the grant application and this was
consistent across all three categories. The average amount of funding
per citation was over $43,900. The largest amount of funding spent on a
single gene with "aging" in the grant abstract was $195 million, which
represents fewer than 5% of the total funding spent on P53 research.
SIRT1 and homologs is the only gene with over $100 million spent on
analyzing its role in aging with just under 14% of the funding spent on
non-aging related projects. Most of the genes related to aging and
longevity were associated with other biologic processes, and most of the
funding and publications citing these genes is related to areas other
than aging.
"While most scientists rely on published research
data and scientific conferences to follow the advances their areas of
research, the vast amount of knowledge is codified in the published
research grant abstracts and associated metadata. A comprehensive
analysis of government grants and related publications shows that aging
research is an emerging field and that only a minor fraction of the
research dollars spent on genes implicated in aging and longevity was
actually intended for aging research," said professor Alex Zhavoronkov,
PhD, director of the Biogerontology Research Foundation, UK.
The
team also performed the signaling pathway analysis of the genes
implicated in aging and longevity and demonstrated that that most of the
gerontogenes are members of the stress response pathways that confirm
the existence of genetics "longevity program." As a rule, genes --
regulators of longevity program -- suppress mild stress response and
mutations that make some of those pathways less efficient and provide
life-extension benefits. Mild overexpression of effector longevity
genes, involved with stress-response to DNA, protein, or other cellular
damages, prolong lifespan. While moderate stress induces "longevity
program" by stimulating expression of life assurance genes and promoting
prevention or elimination of errors, including the novel and
spontaneous ones, chronic or acute stress exposure exhausts the defense
mechanisms and therefore accelerates aging. Pro-aging and anti-aginggene-determined processes exist on all levels of organismal system --
from molecules to systems (metabolic, endocrine, immune, and
inter-cellular communication). Their multi-level organization, the
interpenetration of levels, a combination of regular and stochastic
elements, is what makes the process of aging a fractal process.
Journal Reference: Alexey A Moskalev, Alexander M Aliper, Zeljka Smit-McBride, Anton Buzdin, Alex Zhavoronkov. Genetics and epigenetics of aging and longevity. Cell Cycle, 2014; 13 (7) DOI: 10.4161/cc.28433
Sunday, March 30, 2014
Saturday, March 29, 2014
Genetics of Ageing and Longevity 2014
"Genetics of Ageing and Longevity" - 3rd International Conference (6-10 April, 2014) SOCHI, RUSSIA!
This greatest event of this spring and it is as well important as Olympic games in Sochi 2014!
I just want share to You this best news! Once having started studying aging - you won't be able stop!
I can't stop....
For further information about Conference You may see official site - http://aging-genes2014.com/
This greatest event of this spring and it is as well important as Olympic games in Sochi 2014!
I just want share to You this best news! Once having started studying aging - you won't be able stop!
I can't stop....
Friday, March 21, 2014
In Silico Medicine
You will assume a senior management position with a broad range of responsibilities including:
- working closely with the research and development team of our partner, Pathway Pharmaceuticals, the developer of the OncofFnder and GeroScope tools for personalized medicine;
- establishing collaborations and signing research agreements with the top academic institutions and companies with collections of human transcriptome and RNAseq data;
- maintaining the research progress reports;
- helping manage the office operations;
- collaborate on research articles (there should be many);
- attend and present at conferences;
You will be one of the first members of the In Silico Medicine team with a very steep learning curve and a broad range of responsibilities.
Base compensation:
- Competitive startup salary, significant options package with rapid vesting, travel allowance.
- At this time we can not offer insurance/medical benefits.
Required skills:
- Human transcriptome and RNAseq analysis
- Signaling pathway analysis (experience using either Ingenuity IPA, GeneGo Metacore, Ariadne Genomics or other popular packages)
- Experience working with major drug and compound databases
- Programming skills: Python, MySQL
- Ability to work independently
Preferred:
- close contacts with research groups within major research and clinical institutions in BWI area
- comfortable with Ubuntu, Mac and Windows
- knowledge of the machine learning algorithms
- some experience with C/C++, Java
Education:
- Masters in the relevant area
- PhD degree is preferred
Before applying, please take a look at the following publications:
1. http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00049/full
2. http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00055/abstract (see provisional PDF)
In Silico Medicine is in love with Baltimore and would like to participate in revitalizing the city. We are planning to move our offices into the downtown area close to the JHMI.
About In Silico Medicine:
Through excellence in knowledge management, machine learning and bioinformatics, relentless pursuit for new drug, omics and clinical outcomes data, development of reliable in silico drug screening methods, novel validation approaches and strong international partnerships in personalized medicine we strive to find real working solutions to cure and prevent age-related diseases and aging itself.
This mission will be achieved within within the regulatory frameworks as well as the legal and ethical boundaries and by working with the outstanding scientists, academic and medical institutions and pharmaceutical companies of impeccable credibility.
Our goals are:
1. to become the first and the largest drug discovery company in aging and age-related diseases with practical results;
2. to become the first company to fully implement the concept of personalized science, where medicine is developed, tested and validated for individual patients in a safe high-throughput environment;
Some of our near-term milestones are:
- to develop and validate a set of geroprotecotrs, drugs and therapeutic protocols with aging-suppressive or regenerative properties;
- to validate and improve Geroscope, a system for in silico geroprotector discovery;
- to use Geroscope on a large list of possible geroprotectors to rank them by the predicted efficacy and validate using human cells and on model organisms;
- to develop the most comprehensive scalable drug knowledge management system of annotated drugs, small molecules, biologics and all other factors that may influence the many events on the molecular, cellular and tissue levels;
- to use use our expertise in targeted drug selection based on individual patient's gene expression data and signaling cloud regulation for drug discovery;
- to partner with the top pharmaceutical companies to help analyze their drug databases, lead compounds and to enable them to accurately predict the efficacy of their drugs on patient groups and individual patients;
Please send your resume' or inquiry to:
In Silico Medicine, Inc
www.insilicomedicine.com
fightaging(at)insilicomedicine.com
Friday, March 14, 2014
A scheme guide to changing longevity risk
Unlike in many areas of technology, advances in biomedical
sciences take much longer to move from discovery stage to mass adoption.
As a result, some of the advances made over the past two decades may
only soon be reaching the clinical practice, advances that could result
in unexpected longevity increases for the retired and retiring
population.With this in mind, pension funds and insurance companies must stay vigilant of these new developments, adjusting their policies to hedge against extreme longevity risks while also taking a more proactive role in supporting research that leads to productive longevity and an increase in retirement age.
The longevity dividend
According to the International Aging Research Portfolio the governments of the US, Canada, Australia and the EU have spent more than $700bn (£421bn) on biomedical research since 1994, with the US’s National Institutes of Health spending more than $33bn annually.
In 2011, China also announced a five-year plan to spend $309bn on research and infrastructure in biomedicine.
Government spending, however, only accounts for 40-60 per cent of the total spending on biopharmaceutical research and development, with the 10 largest pharmaceutical companies also collectively spending more than $68bn in 2013 alone.
While a small percentage of this global spending may translate into significant longevity dividends, some discoveries along with convergence of other technologies are expected to significantly reduce mortality.
We are already seeing significant decreases in mortality due to the use of advanced diagnostic technologies, new cardiovascular drugs, targeted anti-cancer therapies and anti-infectives.
Advances in science and technology
The most promising areas of biotechnology that will certainly result in mortality decreases are molecular and genetic diagnostics, biosensors, regenerative medicine technologies, personalised medicine, gene therapy and medical implants.
Take RNA interference technology, first published in 1998, which allows specific genes to be silenced. This technology resulted in a 2006 Nobel Prize for both Andrew Fire and Craig Mello and is already close to clinic, attracting interest from investors and pharmaceutical companies.
Alnylam, a company specialising in RNA interference technologies, was only incorporated in 2002, yet its market capitalisation has already exceeded $5bn and it employs 165 people.
The progress in regenerative medicine is even more apparent, with more than 2,000 companies and research institutions contributing to research, and stem cell products already being used in the clinic.
Wednesday, March 12, 2014
In Silico Medicine Inc. Launches in the US to Use Advances in Technology to Combat Aging and Age-related Diseases
Just fantastic news!
In Silico Medicine Inc, developing novel computer-assisted methods for drug discovery in aging research, has officially launched in the US. In Silico Medicine draws on years of research and software development expertise of its partner, Pathway Pharmaceuticals in Hong Kong, which employs its state of the art OncoFinder platform to select and rate personalized cancer therapies, and identify new drug candidates in oncology.
Population aging is one of the major internal threats to the economies, cultures and social structures in developed countries. Increasing productive longevity of the working population may not only be the major new source of economic growth, but the only altruistic way to save the debt-laden economies from collapsing. And while aging is a very complex multifactorial process that cannot be stopped or reversed by a simple combination of drugs, the pharmaceutical industry needs a platform to screen and predict the effectiveness of possible aging-suppressive drugs in a high-throughput environment to at least slow some of the aging processes
One of the reasons why pharmaceutical companies failed to develop business models for increasing productive human longevity is because human lifespans are much longer than that of the many model organisms and it takes decades to evaluate the effects of any drug. Some of the known drugs have been on the market for many decades and only recently scientists started finding clues to their oncoprotective, cardioprotective and geroprotective effects. Moreover, many drugs that work on model organisms including mice do not have the same effects in humans. There is an urgent need for intelligent systems that will cost-effectively predict the effectiveness of the many drugs on the population, but also on the individual levels.
“We built our platform on years of experience of a large international team who specialize in using gene expression data from individual patient’s tumor to predict the effectiveness of targeted compounds and improve clinical decision making. We are reinventing this system for drug discovery in cancer and aging,” said Alex Zhavoronkov, PhD, the CEO of In Silico Medicine. “The recent wave of startups looking to employ big data to find solutions for aging, including the Google’s Calico and Human Longevity, should give everyone hope that we may see the time when both the medical institutions and pharmaceutical companies will start saving lives so every human being on the planet will benefit.”
Some of the ideas behind the company’s drug discovery platforms for both cancer and aging are rather simple: analyze the genetic and epigenetic profiles of young and normal cells, run computer simulations to see what drugs make the old or malignant cell get as close to the norm as possible and then validate the results on human cells and model organisms. The same approach may be employed to personalize the drug regimen for individual patients. The core expertise of In Silico Medicine is in all-inclusive gene expression analysis and development of various algorithms that minimize the difference between the “young” and “old” signaling pathway activation profiles, and they are actively adding new modules that can be used with the drug databases. These include microRNA, methylation and proteomics modules among others.
About In Silico Medicine Inc (http://www.insilicomedicine.com)
Since 2008 the research team behind In Silico Medicine has worked hard to develop the most comprehensive scalable drug knowledge management system of annotated drugs, small molecules, biologics and all other factors that may influence the many events on the molecular, cellular and tissue levels. The company uses their expertise in targeted drug selection based on individual patient’s gene expression data and signaling cloud regulation for drug discovery in oncology and aging. The longer term goal of In Silico Medicine is to partner with the top pharmaceutical companies to help analyze their drug databases and lead compounds, improve enrollment into clinical trials, and to enable them to accurately predict the efficacy of their drugs on patient groups and individual patients.
In Silico Medicine Inc, developing novel computer-assisted methods for drug discovery in aging research, has officially launched in the US. In Silico Medicine draws on years of research and software development expertise of its partner, Pathway Pharmaceuticals in Hong Kong, which employs its state of the art OncoFinder platform to select and rate personalized cancer therapies, and identify new drug candidates in oncology.
Population aging is one of the major internal threats to the economies, cultures and social structures in developed countries. Increasing productive longevity of the working population may not only be the major new source of economic growth, but the only altruistic way to save the debt-laden economies from collapsing. And while aging is a very complex multifactorial process that cannot be stopped or reversed by a simple combination of drugs, the pharmaceutical industry needs a platform to screen and predict the effectiveness of possible aging-suppressive drugs in a high-throughput environment to at least slow some of the aging processes
One of the reasons why pharmaceutical companies failed to develop business models for increasing productive human longevity is because human lifespans are much longer than that of the many model organisms and it takes decades to evaluate the effects of any drug. Some of the known drugs have been on the market for many decades and only recently scientists started finding clues to their oncoprotective, cardioprotective and geroprotective effects. Moreover, many drugs that work on model organisms including mice do not have the same effects in humans. There is an urgent need for intelligent systems that will cost-effectively predict the effectiveness of the many drugs on the population, but also on the individual levels.
“We built our platform on years of experience of a large international team who specialize in using gene expression data from individual patient’s tumor to predict the effectiveness of targeted compounds and improve clinical decision making. We are reinventing this system for drug discovery in cancer and aging,” said Alex Zhavoronkov, PhD, the CEO of In Silico Medicine. “The recent wave of startups looking to employ big data to find solutions for aging, including the Google’s Calico and Human Longevity, should give everyone hope that we may see the time when both the medical institutions and pharmaceutical companies will start saving lives so every human being on the planet will benefit.”
Some of the ideas behind the company’s drug discovery platforms for both cancer and aging are rather simple: analyze the genetic and epigenetic profiles of young and normal cells, run computer simulations to see what drugs make the old or malignant cell get as close to the norm as possible and then validate the results on human cells and model organisms. The same approach may be employed to personalize the drug regimen for individual patients. The core expertise of In Silico Medicine is in all-inclusive gene expression analysis and development of various algorithms that minimize the difference between the “young” and “old” signaling pathway activation profiles, and they are actively adding new modules that can be used with the drug databases. These include microRNA, methylation and proteomics modules among others.
About In Silico Medicine Inc (http://www.insilicomedicine.com)
Since 2008 the research team behind In Silico Medicine has worked hard to develop the most comprehensive scalable drug knowledge management system of annotated drugs, small molecules, biologics and all other factors that may influence the many events on the molecular, cellular and tissue levels. The company uses their expertise in targeted drug selection based on individual patient’s gene expression data and signaling cloud regulation for drug discovery in oncology and aging. The longer term goal of In Silico Medicine is to partner with the top pharmaceutical companies to help analyze their drug databases and lead compounds, improve enrollment into clinical trials, and to enable them to accurately predict the efficacy of their drugs on patient groups and individual patients.
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