Tuesday, October 1, 2013

New ways to combat age-related mineralization

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).

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.

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