Wednesday, March 5, 2014

From Cancer to Aging Drug Discovery

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 the 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


Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprote...

Tuesday, October 1, 2013

Mineralization of the connective tissue with age may be involved in cancer


When you open a 70-year old patient on the operating table and touch the aorta, the feeling may resemble touching an eggshell or sand paper. It is stiffer than the heart of a young person and the key reasons for this are the abundant calcium deposits in the connective tissue that accumulate with age.

The many factors leading to mineralization of the connective tissue include genetic and acquired diseases, inflammation, reactive oxygen species, but the major problem is that it occurs spontaneously during aging as calcium-containing molecules are trapped in the extracellular matrix and develop into apatite over time.

Despite its relative significance, compared to the many other areas of aging research, mineralization of the connective tissue is rarely mentioned in scientific publications and few teams are working on preventing or clearing out the extracellular aggregates.  To address the problem, a multidisciplinary team of physicians, bioinformatitians, biochemists and physicists performed a comprehensive bioinformatics analysis of the many factors involved in mineralization, identified key molecular targets and proposed a list of possible drugs to address the issue.

The results of the study were accepted for publication by a high-impact journal in biogerontology “Rejuvenation Research” and will be published shortly and can be cited as “Mineralization of the connective tissue: a complex molecular process leading to age-related loss of function”, Anastasia Shindyapina, Garik V Mkrtchyan, Tatiana Gneteeva, Sveatoslav Buiucli, M Kulka, B Tancowny, Alexander Aliper, Alexander Zhavoronkov, Rejuvenation Research, ahead of print. doi:10.1089/rej.2013.1475, http://online.liebertpub.com/doi/abs/10.1089/rej.2013.1475 , PMID 23902273

Anastasia Shindyapina together with her collaborators presented the results of the study on the 5th of September at the SENS6 conference in Cambridge, UK.

“Aging inevitably leads to the loss of function on many levels. Mineralization of the connective tissue is one of the causes and consequences of aging and is a complex multifactorial process. Metabolic activity, diseases and external stress factors may cause calcification, but most importantly, it occurs spontaneously. Our goal is to identify least toxic ways to both prevent calcification and to repair the accumulated  aggregates.”, said Anastasia Shindyapina, ASUS Fellow for Bioinformatics and Medical Information Technology, PhD-candidate at the Moscow State University and researcher at FOIRMYS.


"Mineralization of connective tissue with age is one of the many aspects of aging that are examples of "accumulation of eventually pathogenic extracellular material", an issue that attracts too little attention within the academic community. The accumulation of advanced glycation endproducts (AGEs) and of mineral deposits both result in increased stiffness of connective tissue, impair homeostasis and contribute to a broad range of age-related diseases. Through comprehensive bioinformatic analysis of the many molecular processes involved in mineralization, Zhavoronkov's team has identified possible molecular interventions. Additionally they proposed that mineralization and AGEs work in concert and should be addressed concurrently. Anastasia Shyndyapina, the lead author on the paper, recently presented this work at the SENS6 conference in Cambridge.", commented Dr. Aubrey de Grey, Chief Science Officer of SENS Research Foundation and International Adjunct Professor at the Moscow Institute of Physics and Technology (MIPT).

About FOIRMYS
The First Open Institute for Regenerative Medicine for Young Scientists (FOIRMYS) is a non-profit volunteer initiative bringing together over a thousand enthusiast young scientists and physicians interested in regenerative medicine. It was first organized by Alex Zhavoronkov, PhD in collaboration with Sergey Yakovenko, PhD, Sergey Roumiantsev, PhD and Oleg Korzinov in Moscow with support from Anna Chapman.
FOIRMYS provides regular weekly lectures by the top academic and industry thought leaders, investors and regulators. The list of presenters includes Paolo Macchiarini (Karolinska Institute), Alexey Aravin (Caltech), Charles Cantor (Boston U, ex-director of the Human Genome Project), Augustinus Bader (Leipzig University), top managers from Beijing Genomics Institute, Malaysian Genome Resource Center, Indigo Capital Partners and many others. As part of the curriculum students participate in practicums at “Altravita IVF, FRCCPH, FORCC, Quantum Pharmaceuticals, Biopharmcluster “Northern” and Moscow Institute of Physics and Technology.
Members work in small teams comprised of scientists and physicians on ambitious outlier projects in aging and regenerative medicine with topics ranging from mineralization of connective tissue, HGPS and regulation of endometriosis to industry overviews and healthcare economics. The projects are coordinated in a crowdsourced environment and rely heavily on popular tools like Facebook, Dropbox and Google Apps. FOIRMYS developed a concept called “Personalized Medicine”, where projects are centered around the problems of a single patient, who provides samples and helps coordinate the project. Members also learn how to promote their work, create personal science blogs (including Women in Science initiative) and engage in industry outreach.
Participation in practical group projects resulted in success stories including young scientists’ publications in peer-reviewed journals, fellowships, participation in international conferences, gainful employment of young scientists and international collaborations.

Wednesday, May 15, 2013

One book to pre-order for the Summer – Ageless Generation: How Advances in Biomedicine Will Transform the Future of the Global Economy


The end of retirment by extending healthy life or by an unprecedented economic collapse
 If you were to pre-order one book for this Summer consider this one. The Ageless Generation: How Advances in Biomedicine Will Transform the Future of the Global Economy.

Accelerating aging research to extend healthy productive lifespan seems to be in everyone's best interest. There are few people on this planet, who would chose to age and gradually succumb to diseases of aging if they were given a choice to live longer and healthier lives.

However, up until recently, the many failed promises of science made many of us resistant to accepting the possibility of the interventions that may take us way beyond the lifespans of our parents and grandparents.
Well, now it is time to open up to these possibilities and get actively involved, because the urgency to accelerate aging research now stems from the economic fundamentals of the aging population in the developed countries.

Aging populations in the developed countries are now the single biggest threat to the global economy. People that are retiring today and that are due to retire in the next decade are going to live extraordinarily long lives due to the advances in biomedicine and propagation of these advanced into the clinical setting.
 
 "The Ageless Generation: How Advances in Biomedicine Will Transform the Global Economy",  a book by Alex Zhavoronkov, PhD in very simple layman language drills down into the history of retirement and social security and the present state of the social security, healthcare and the unfunded liabilities of the developed countries. It also takes the reader on a tour of the laboratories in the US, Europe and China, where scientists toil on solving the complex puzzles of regenerative medicine, longevity genes and technologies that will extend our lifespans. Then it looks at the future of retirement and presents the real possibility of the near-term Economic Collapse. There are some solutions and policy proposals, but chances are very small that we will be able to avoid the crisis before we can significantly extend healthy lifespans.

The book will be published by Palgrave Macmillan in June 2013 and is available for pre-order at Amazon and most bookstores worldwide.

Amazon:
http://www.amazon.com/Ageless-Generation-Advances-Biomedicine-Transform/dp/0230342205/
Barnes and Noble: 
http://www.barnesandnoble.com/w/the-ageless-generation-alex-zhavoronkov/1113106743

The main idea of this book is that in record time the US must start a coordinated program to increase healthy productive lives of the two generations that are nearing retirement or the whole world will face several decades of economic decline and possible collapse. The need to fight aging is no longer an altruistic initiative, but a real economic necessity.

Recent advances in biomedicine will extend the lifespans of the two generations due to retire within the next twenty years; however, unless there are programs in place to keep them healthy and working, the burden of the aging population will drive the global economy into the state of depression or even worse. Developed countries should re-focus the research programs from just extending lifespans to extending health spans and the retirement age to remain solvent and this initiative must be led by the beating heart and the brain of the world's economy - the United States of America.

Every reader of this post must consider the possibility of radical extension of healthy life through biomedicine. One thing you should do right now is to stretch the expected horizons to 150 years.  Yes, it is possible! Even if we let some of the major advances that already happened to converge and reach the clinic, 150 years of life is the very minimum of what a 40-year old today should expect.

One way to prepare for it is to pack up and prepare yourself and your family to live through the economic collapse. Another way is to actively engage in supporting aging research by engaging in government lobbying, supporting research directly or even engaging in research personally.

Here is a link to Macmillan's page for this book: http://us.macmillan.com/theagelessgeneration/AlexZhavoronkov 

And here is a Facebook page: https://www.facebook.com/TheagelessGeneration 

Wednesday, April 17, 2013

One facinating female scientist from Russia

Russia as the country may not be contributing much to the global progress in biomedicine, but without doubt it gives birth to many bright scientists.

One of such rare gems is Maria Litovchenko, a student at the Moscow Institute of Physics and Technology, scientist at the FRC Center for Pediatric Hematology, Oncology and Immunology, research associate at the Biogerontology Research Foundation and the organizer of the First Open Institute for Regenerative Medicine for Young Scientists. All that before turning 20!

We recently reviewed her paper on possible novel approaches to ameliorating progeria in kids.

When she is not working at the lab or sleeping, she is either programming or initiating the outreach programs to promote women in science. She is an avid advocate of aging research.

This week she is presenting at TEDMED Russia with a talk "Power to the Patient: From Personalized Medicine to Personalized Science".



Kudos, Maria!

Maria's Science Blog


You should definitely take a look at her ABOUT US page.

Monday, March 14, 2011

A REVOLUTIONARY NEW TOOL FOR BIOMEDICAL RESEARCH: AGINGPORTFOLIO.ORG

While we still like the NIH RePORT tool, there is another great resource for analyzing grants, publications and other research materials in biomedical science - The International Aging Research Portfolio .

We performed a search using "cancer biomarker" in the advanced search and got great results. These are only top 25 results, but it is possible to see almost all of them at once and the Spore Grants have excellent descriptions.

We went ahead and Liked them at their FaceBook Page!

It is also possible to see the results as graphs and play around with the statistics.


Search results

Search Keywords In:  Title, Description, Tags
Keywords:  "cancer biomarker"
Total Funding: $ 137,209,529
Number Of Funding: 304
Number Of Projects: 302
Project Funding

Project number

Project title

Investigators

Recipient organization

Funding organization

Year

Funding
1U24CA126476-01Measuring cancer biomarker candidates by targeted ms and ab enrichmentCARR STEVENAMASSACHUSETTS INSTITUTE OF TECHNOLOGYNATIONAL CANCER INSTITUTE 2006$2,904,3044
5U24CA126476-05Measuring cancer biomarker candidates by targeted ms and ab enrichmentCARR STEVENABROAD INSTITUTE, INC.NATIONAL CANCER INSTITUTE 2009$2,833,8584
5U24CA126476-02Measuring cancer biomarker candidates by targeted ms and ab enrichmentCARR STEVENAMASSACHUSETTS INSTITUTE OF TECHNOLOGYNATIONAL CANCER INSTITUTE 2007$2,764,9194
5U54CA116847-02Mechanisms of energy balance and cancer preventionMCTIERNAN ANNEMFRED HUTCHINSON CANCER RESEARCH CENTERNATIONAL CANCER INSTITUTE 2006$2,506,3200
2P50CA058184-09Spore in lung cancerBAYLIN STEPHENBJOHNS HOPKINS UNIVERSITYNATIONAL CANCER INSTITUTE 2003$2,500,0004
5P50CA058184-10Spore in lung cancerBAYLIN STEPHENBJOHNS HOPKINS UNIVERSITYNATIONAL CANCER INSTITUTE 2004$2,491,5314
5P50CA058184-11Spore in lung cancerBAYLIN STEPHENBJOHNS HOPKINS UNIVERSITYNATIONAL CANCER INSTITUTE 2005$2,490,1654
5U54CA116847-04Mechanisms of energy balance and cancer preventionMCTIERNAN ANNEMFRED HUTCHINSON CANCER RESEARCH CENTERNATIONAL CANCER INSTITUTE 2008$2,478,4290
1U54CA116847-01Mechanisms of energy balance and cancer preventionMCTIERNAN ANNEMFRED HUTCHINSON CANCER RESEARCH CENTERNATIONAL CANCER INSTITUTE 2005$2,472,7580
5U54CA116847-03Mechanisms of energy balance and cancer preventionMCTIERNAN ANNEMFRED HUTCHINSON CANCER RESEARCH CENTERNATIONAL CANCER INSTITUTE 2007$2,463,2120
5U54CA116847-05Mechanisms of energy balance and cancer preventionMCTIERNAN ANNEMFRED HUTCHINSON CANCER RESEARCH CENTERNATIONAL CANCER INSTITUTE 2009$2,461,3280
5P50CA058184-12Spore in lung cancerBAYLIN STEPHENBJOHNS HOPKINS UNIVERSITYNATIONAL CANCER INSTITUTE 2006$2,430,3294
5P50CA058184-13Spore in lung cancerBAYLIN STEPHENBJOHNS HOPKINS UNIVERSITYNATIONAL CANCER INSTITUTE 2007$2,359,8504
2P50CA058184-14A1Spore in lung cancerBAYLIN STEPHENBJOHNS HOPKINS UNIVERSITYNATIONAL CANCER INSTITUTE 2009$2,300,0000
R44CA139803-02Field of injury based biomarkers for lung cancerHALLAM EALLEGRO DIAGNOSTICS, INC.NATIONAL CANCER INSTITUTE 2010$1,823,0814
5U24CA126476-03Measuring cancer biomarker candidates by targeted ms and ab enrichmentCARR STEVENAMASSACHUSETTS INSTITUTE OF TECHNOLOGYNATIONAL CANCER INSTITUTE 2008$1,758,2224
7U24CA126477-02Targeted and global proteomic strategies for early breast cancer detectionFISHER SUSANJUNIVERSITY OF CALIFORNIA SAN FRANCISCONATIONAL CANCER INSTITUTE 2006$1,711,4030
P50CA058184-15Spore in lung cancerBAYLIN BJOHNS HOPKINS UNIVERSITYNATIONAL CANCER INSTITUTE 2010$1,710,0380
5U24CA126477-04Targeted and global proteomic strategies for early breast cancer detectionFISHER SUSANJUNIVERSITY OF CALIFORNIA SAN FRANCISCONATIONAL CANCER INSTITUTE 2008$1,642,1720
5U24CA126477-03Targeted and global proteomic strategies for early breast cancer detectionFISHER SUSANJUNIVERSITY OF CALIFORNIA SAN FRANCISCONATIONAL CANCER INSTITUTE 2007$1,539,2720
1R01CA105274-01A1Prospective study of breast cancer survivorshipKUSHI LAWRENCEHKAISER FOUNDATION RESEARCH INSTITUTENATIONAL CANCER INSTITUTE 2004$1,487,1144
1U24CA126480-01Apt: the analytical proteomics teamREGNIER FREDEPURDUE UNIVERSITY WEST LAFAYETTENATIONAL CANCER INSTITUTE 2006$1,264,6084
5U24CA126480-02Apt: the analytical proteomics teamREGNIER FREDEPURDUE UNIVERSITY WEST LAFAYETTENATIONAL CANCER INSTITUTE 2007$1,193,0244
3P50CA058184-13S1Spore in lung cancerBAYLIN STEPHENBJOHNS HOPKINS UNIVERSITYNATIONAL CANCER INSTITUTE 2008$1,179,9254
5U24CA126480-03Apt: the analytical proteomics teamREGNIER FREDEPURDUE UNIVERSITY WEST LAFAYETTENATIONAL CANCER INSTITUTE 2008$1,164,3584

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View 1 - 25 of 304

Friday, January 28, 2011

New epigenetic biomarker test for melanoma?

In a paper that recently appeared online in the journal Pigment Cell & Melanoma Research, a team of UNC researchers tested whether DNA methylation profiling could be accomplished on melanoma and mole tissues that had been preserved in fixatives for typical pathology examination after biopsy. They found that results on tissues prepared in this way were reliable and DNA methylation distinguished malignant melanomas from non-malignant moles.

http://www.sciencedaily.com/releases/2011/01/110124102925.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29&utm_content=Google+Feedfetcher

Signal Transduction Pathways

Signal Transduction Pathways
RTK, GPCR, GF, Cytokine, Wnt, Death Factors & Shh pathways