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Tasakova O.S., Golubtsova N.N., Gunin A.G.
Thioredoxin antioxidant system and replicative aging of fibroblasts – analysis of interconnection and role in human skin
Keywords: dermis, fibroblasts, thioredoxin, thioredoxin reductase, thioredoxin-binding protein, aging
One of the key components of cell protection against oxidative damage is the thioredoxin system, which includes thioredoxin, thioredoxin reductase, and thioredoxin-binding protein. To date, there is no convincing evidence confirming the role of oxidative stress in the development of natural aging, so this area of research remains relevant. The aim of the study was to analyze the relationship between age–related changes in the expression of thioredoxin system proteins and the proliferation activity of dermal fibroblasts during intrauterine development and natural aging of human skin. Material and methods. The research material was autopsies of fetal skin and of people of both sexes. Immunohistochemistry was used to identify the expression of thioredoxin, thioredoxin reductase, thioredoxin-binding protein and proliferating cell nuclear antigen. Results. In the intrauterine period, the content of fibroblasts with IHC-detectable proteins of the thioredoxin system is no more than 2%, while about half of dermal fibroblasts express PCNA. Apparently, the thioredoxin system in fetal skin has no effect on proliferation of dermal fibroblasts. Immediately after birth and up to 85 years of age, the proportion of dermal fibroblasts containing proteins of the thioredoxin system increases significantly (p < 0.05). The age-related increase in the number of fibroblasts with a positive thioredoxin stain can be considered as an adaptive process in response to the appearance of thioredoxin substrates in cells. However, progressive increase in the effect of thioredoxin proteins in the dermis from birth to 85 years of age is generally inversely proportional to the proliferative activity of fibroblasts. Nevertheless, it is likely that the ratio of thioredoxin proteins in dermal fibroblasts is important in each age period, which is crucial for regulating proliferation/apoptosis of the main dermis cells. Conclusions. 1. The replicative aging of human dermal fibroblasts is inversely correlated with the expression of thioredoxin complex proteins. 2. In the intrauterine period, the most intense proliferation of dermal fibroblasts is observed, which is not regulated by thioredoxin-mediated mechanisms. 3. An increase in the expression of thioredoxin system proteins in the postnatal period coincides with a decrease in the proliferative activity of dermal fibroblasts. 4. The useful effect of the thioredoxin system on proliferation in each age period is associated with the activity of the thioredoxin system components in a fibroblast.
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About authors
- Tasakova Olga S.
- Cardiologist, Cardiology Department No. 3, Republican Cardiology Dispensary, Russia, Cheboksary (olya.tasakova@mail.ru; ORCID: https://orcid.org/0000-0003-2089-2205)
- Golubtsova Natalya N.
- Doctor of Biological Sciences, Associate Professor, Head of the Department of General and Clinical Morphology and Forensic Medicine, Chuvash State University, Russia, Cheboksary (golubnata@list.ru; ORCID: https://orcid.org/0000-0002-5436-1333)
- Gunin Andrei G.
- Doctor of Medical Sciences, Professor, Department of Obstetrics and Gynecology named after G.M. Vorontzova, Chuvash State University, Russia, Cheboksary (drgunin@mail.ru; ORCID: https://orcid.org/0000-0001-8383-5190)
Article link
Tasakova O.S., Golubtsova N.N., Gunin A.G. Thioredoxin antioxidant system and replicative aging of fibroblasts – analysis of interconnection and role in human skin [Electronic resource] // Acta medica Eurasica. – 2025. – №2. P. 31-39. – URL: https://acta-medica-eurasica.ru/en/single/2025/2/4/. DOI: 10.47026/2413-4864-2025-2-31-39.