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.