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Metformin slows down ageing processes at the cellular level in SHR mice

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Abstract

It has been shown recently that metformin, the indirect mTOR-kinase inhibitor, significantly increases medium (by 37.8 %) and maximum (by 10.3 %) life span of SHR mice (Anisimov et al., 2008). We obtained fibroblasts from skin of 11-, 16-, 19- and 23-months-old SHR mice treated with metformin since the third and ninth day of life. We studied markers of cellular senescence in these fibroblasts. Significant differences were observed between the average number of senescence-associated heterchromatic foci (SAHF), the average of area nuclei and fluorescence intensity of nucleus after staining for y-H2AX in control and experimental animals. Also, we showed that metformin prevented the accumulation of fibroblasts with large area of nuclei; high activity of senescence-associated P-galactosidase (SA-(3-gal), and high fluorescence intensity after staining for y-H2AX. It appears that accumulation of large quantity of senescence markers within a cell triggers it to enter the aging process. It appears that the increase of “old” cell population above the threshold disrupts the normal function of certain tissues, organs, and finally, the whole organism. It appears that metformin delays the “old” cells accumulation and prolongs the organism youth.

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Abbreviations

mTOR:

mammalian target of rapamycin

AMPK:

AMP-activated serinethreonine kinase

SAHF:

senescence-associated heterochromatin foci

SA-β-gal:

senescence-associated β-galactosidase

IGF-1:

insulin-like growth factor-1

γ-H2AX:

phosphorylated form of histone H2AX

IF:

intensity of fluorescence

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Authors and Affiliations

  1. Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia

    A. V. Arkadieva, V. M. Mikhelson & I. M. Spivak

  2. Petrov Research Institute of Oncology, St. Petersburg, Russia

    I. G. Popovich & V. N. Anisimov

  3. St. Petersburg State University, St. Petersburg, Russia

    A. A. Mamonov

Authors
  1. A. V. Arkadieva
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  2. A. A. Mamonov
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  3. I. G. Popovich
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  4. V. N. Anisimov
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  5. V. M. Mikhelson
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  6. I. M. Spivak
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Correspondence to A. V. Arkadieva.

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Original Russian Text © A.V. Arkadieva, A.A. Mamonov, I.G. Popovich, V.N. Anisimov, V.M. Mikhelson, I.M. Spivak, 2011, published in Tsitologiya, Vol. 53, No. 2, 2011, pp. 166–174.

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Arkadieva, A.V., Mamonov, A.A., Popovich, I.G. et al. Metformin slows down ageing processes at the cellular level in SHR mice. Cell Tiss. Biol. 5, 151–159 (2011). https://doi.org/10.1134/S1990519X11020027

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