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Invited researcher Vadim Nikolayevich Gladyshev
Contract number
14.W03.31.0012
Time span of the project
2017-2021

As of 30.01.2020

13
Number of staff members
3
scientific publications
General information

Name of the project: Protein synthesis in aging and life expectancy control

Strategy for Scientific and Technological Development Priority Level: в


Goals and objectives

Research directions:

- Study of aging-related changes in living organisms at the molecular and the cell levels with a special focus on mechanisms of supporting proteostasis and protein biosynthesis regulation

- Study of causes of changes in mortality

- Comparative and evolutionary genomics

- Research of changes of aging markers in the setting of cell reprogrammming

Project objective: Analysis of biosynthesis of proteins at the system level in organs and tissues of animals, determining its changes depending on diet, usage of medications and other circumstances


The practical value of the study

  • We have obtained and analyzed data of ribosome profiling of liver and kidney taken from mice of different ages. The analysis has shown systematic changes in gene expression at the translation level that correlate with age and affect genes related to immunity, inflammation, metabolism and biosynthesis of proteins (in particular, drop of mRNA transcription regulated by the mTOR kinase).
  • Our researchers have identified regions of transcripts of repeated elements of genome that are actively translated in somatic cells of mice.
  • The Laboratory has developed a method for measuring expression of luciferase in transfected cultivated cells of mammals in teal time in live mice transfected with modified mRNA-transcripts.
  • We have developed a method for fast assessment of speed of replicative aging of hops and conducted screening of mutant strains to determine frequency of early mortality.
  • Our team have explained that the U-shape of the mortality curve is caused by increase of negative aging changes and reduction of the number of mice with inferior combinations of alleles.

Education and career development:

  • The leading scientist has developed and read a lecture course in English «Systems biology of aging», for fifth year students of the Faculty of Bioengineering and Bioinformatics of the Moscow State University (Russia).
  • We have organized internships at the laboratory of the Harvard Medical School in Boston (USA) for its employees.

Other results:

The «Frontiers in Aging» conference has been planned and conducted in 2018 with support from the Faculty of Fundamental Medicine of the Moscow State University and the Medical Research and Education Center of the Moscow State University. The conference was attended by over 150 participants, the program featured presentations by leading world class professionals in aging research and life expectancy control including participants from the USA, Germany, Singapore, China PR and Russia (apart from Moscow – in Dolgoprudniy, Saint Petersburg, Syktyvkar).

Collaborations:

  • GladyshevLab Redox Biology, Aging & Selenium, Harvard Medical School (USA): mastering the method of ribosome profiling of mouse organs, obtaining fibroblasts of mice of different ages
  • A. N. Belozerskiy Laboratory of the Research Institute of Physical and Chemical Biology of the Moscow State University (Russia): high output sequencing libraries for ribosome profiling and RNA squencing
  • Laboratory of Chemistry of Nucleoproteids of the Faculty of Chemistry of the Moscow State University (Russia): producing genetically modified mice
  • Skoltech Center for Translational Biomedicine (Russia): developing a method of mRNA-transfection of liver cells of live mice

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Ma S., Gladyshev V.N.
Molecular signatures of longevity: Insights from cross-species comparative studies. Seminars in Cell and Developmental Biology 70: 190–203 (2017).
Anisimova A.S., Alexandrov A.I., Makarova N.E., Gladyshev V.N., Dmitriev S.E.
Protein synthesis and quality control in aging. Aging (Albany NY), 10(12): 4269-4288 (2018).
Galkin F., Zhang B., Dmitriev S.E., Gladyshev V.N.
Reversibility of irreversible aging. Ageing Research Reviews 49: 104-114 (2019).
Young D.J., Makeeva D.S., Zhang F., Anisimova A.S., Stolboushkina E.A., Ghobakhlou F., Shatsky I.N., Dmitriev S.E., Hinnebusch A.G., Guydosh N.R.
Tma64/eIF2D, Tma20/MCT-1, and Tma22/DENR Recycle Post-termination 40S Subunits In Vivo. Molecular Cell 71(5): 761-774 (2018).
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