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Contract number
Time span of the project

As of 01.11.2022

Number of staff members
scientific publications
General information

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

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

Scientific results:

  1. Using ribosome profiling, we have described changes in protein biosynthesis in the liver and kidneys during aging. 
  2. We have developed svist4get, software to visualize ribosome profiling data. 
  3. A model has been developed that describes the complex dynamics of mortality  in the human population as a resultant between the diminishing child mortality related to selection and the increasing mortality due to aging which started before birth. 
  4. We have determined signatures of transcription changes happening in organs of mice when life-prolonging interventions are made. 
  5. We have determined changes occurring in organs of mice with depletion of the eEF2 translation factor (deceleration of translation). 
  6. Using a yeast model, we have demonstrated that replacing a gene with a knockout cassette can lead to aberrative changes of the level of expression of adjacent genes in a mechanism related to the regulation. 
  7. It has been demonstrated that the cyclic induction of the FOXM1 transcription factor in mice delays the development of natural and progeroid aging and prolongs life.

Education and career development:

  • 3 Candidate of Sciences, 2 Doctor of Sciences dissertations have been prepared and defended.
  • 4 lecture courses have been developed.
  • 5 lecture courses and laboratory case studies have been created.
  • Number of students who defended their graduation qualification works in the Laboratory over the course of its existence: 15.
  • Number of postgraduate students who have worked in the Laboratory over the course of its existence: 8. 

Organizational and infrastructural transformations:

We have established work and service of general-use devices:

  • MACS Quant flow-through cytofluorometer.
  • CLARIOstar multi-modal tablet reader. 
  • Brigham and Women’s Hospital, Harvard Medical School: joint projects, articles, internships of employees of the Laboratory.
  • Skolkovo Institute of Science and Technology: joint scientific project.

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anisimova as, alexandrov ai, makarova ne, gladyshev vn, dmitriev se.
Protein synthesis and quality control in aging. Aging (Albany NY). 2018, 10(12): 4269-4288.
galkin f, zhang b, dmitriev se, gladyshev vn.
Reversibility of irreversible aging. Ageing Res Rev. 2019, 49: 104-114.
tyshkovskiy a, bozaykut p, borodinova aa, gerashchenko mv, ables gp, garratt m, khaitovich p, clish cb, miller ra, gladyshev vn.
Tma64/eIF2D, Tma20/MCT-1, and Tma22/DENR Recycle Post-termination 40S Subunits In Vivo. Mol Cell. 2018, 71(5): 761-774.e5.
kinzina ed, podolskiy di, dmitriev se, gladyshev vn.
Identification and Application of Gene Expression Signatures Associated with Lifespan Extension. Cell Metab. 2019, 30(3): 573-593.e8.
gerashchenko mv, nesterchuk mv, smekalova em, paulo ja, kowalski ps, akulich ka, bogorad r, dmitriev se, gygi s, zatsepin t, anderson dg, gladyshev vn, koteliansky ve
Patterns of Aging Biomarkers, Mortality, and Damaging Mutations Illuminate the Beginning of Aging and Causes of Early-Life Mortality. Cell Rep. 2019 29(13):4276-4284.e3.
anisimova as, meerson mb, gerashchenko mv, kulakovskiy iv, dmitriev se, gladyshev vn.
Translation elongation factor 2 depletion by siRNA in mouse liver leads to mTOR-independent translational upregulation of ribosomal protein genes. Sci Rep. 2020 10(1):15473
egorov aa, alexandrov ai, urakov vn, makeeva ds, edakin ro, kushchenko as, gladyshev vn, kulakovskiy iv, dmitriev se.
Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel. Nat Chem Biol. 2020 16(10):1071-1077.
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