Advances in Gerontology

, Volume 9, Issue 1, pp 81–85 | Cite as

The Influence of Metformin on Age-Related Changes in the Number and Proliferation of Dermal Fibroblasts in Mice

  • A. G. GuninEmail author
  • N. N. Golubtsova
  • N. O. Subbotkina
  • A. S. Subbotkin


The goal of the work was to examine the effects of metformin on age-related changes in the number and proliferation of dermal fibroblasts in mice. The dermis was examined in 5-month-old mice that received drinking water with metformin at a concentration of 500 mg/L from the age of 2 months (within 90 days). Five-month-old mice that received drinking water without metformin were used as a control. Material from 2-month-old mice was also used in the work. We have counted the total number of dermal fibroblasts and a portion of fibroblasts with positive staining for the Ki-67 antigen. The results showed that there was a decrease in the total number of mouse dermal fibroblasts by 42.3% from two up to 5 months of life and in the proportion of fibroblasts with positive staining for Ki-67 by 12%. The total number of dermal fibroblasts in 5-month-old mice was 13.4% lower under the effect of metformin. The proportion of fibroblasts with positive staining for Ki-67 was reduced by 27.3% as compared to animals that did not receive metformin. Thus, the age-related decrease in dermal fibroblasts of mice is due to the decline in their proliferation activity. Metformin has an inhibitory effect on the proliferation of dermal fibroblasts in mice.


dermis fibroblasts metformin Ki-67 proliferation 



This study was supported by the Russian Foundation for Basic Research, projects nos. 16-44-210018 and 18-04-00024.


Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The study was approved by the Ethics Committee at the Faculty of Medicine (Ulyanov Chuvash State University).


  1. 1.
    Anisimov, V.N., Antidiabetic biguanide metformin as geroprotector and anticarcinogen, Ozhirenie Metab., 2011, no. 3, pp. 18–24.Google Scholar
  2. 2.
    Anisimov, V.N., Popovich, I.G., Egormin, P.A., et al., Use of antidiabetic biguanides for the prevention and treatment of cancer: the results of preclinical trials, Vopr. Onkol., 2016, vol. 62, no. 2, pp. 234–244.Google Scholar
  3. 3.
    Arkadieva, A.V., Mamonov, A.A., Popovich, I.G., Anisimov, V.N., Mikhelson, V.M., and Spivak, I.M., Metformin slows down ageing processes at the cellular level in SHR mice, Cell Tissue Biol., 2011, vol. 5, no. 2, pp. 151–159.CrossRefGoogle Scholar
  4. 4.
    Gritsenko, D.A., Orlova, O.A., Linkova, N.S., and Khavinson, V.Kh., Transcription factor p53 and skin aging, Adv. Gerontol., 2017, vol. 7, no. 2, pp. 114–119.CrossRefGoogle Scholar
  5. 5.
    Chetina, E.V., Nutrient signaling pathways and rheumatic diseases, Nauchno-Prakt. Revmatol., 2013, vol. 51, no. 3, pp. 313–323.Google Scholar
  6. 6.
    Al-Wahab, Z., Mert, I., Tebbe, C., et al., Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction, Oncotarget, 2015, vol. 6, no. 13, pp. 10 908–21 093.CrossRefGoogle Scholar
  7. 7.
    Gunin, A.G., Petrov, V.V., Golubtzova, N.N., et al., Age-related changes in angiogenesis in human dermis, Exp. Gerontol., 2014, vol. 55, pp. 143–151.CrossRefGoogle Scholar
  8. 8.
    Liu, Y., Zhang, Y., Jia, K., et al., Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway, Exp. Ther. Med., 2015, vol. 9, no. 4, pp. 1401–1406.CrossRefGoogle Scholar
  9. 9.
    Rinnerthaler, M., Bischof, J., Streubel, M.K., et al., Oxidative stress in aging human skin, Biomolecules, 2015, vol. 5, no. 2, pp. 545–589.CrossRefGoogle Scholar
  10. 10.
    Shaw, R.J., Bardeesy, N., Manning, B.D., et al., The LKB1 tumor suppressor negatively regulates mTOR signaling, Cancer Cell, 2004, vol. 6, pp. 91–99.CrossRefGoogle Scholar
  11. 11.
    Tomic, T., Botton, T., Cerezo, M., et al., Metformin inhibits melanoma development through autophagy and apoptosis mechanisms, Cell Death Dis., 2011, vol. 2, p. e199.CrossRefGoogle Scholar
  12. 12.
    Viollet, B., Guigas, B., Garcia, N.S., et al., Cellular and molecular mechanisms of metformin: an overview, Clin. Sci., 2012, vol. 122, pp. 253–270.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • A. G. Gunin
    • 1
    Email author
  • N. N. Golubtsova
    • 1
  • N. O. Subbotkina
    • 1
  • A. S. Subbotkin
    • 1
  1. 1.Chuvash State UniversityCheboksaryRussia

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