Immunohistochemical study of mTOR⁺ fibroblasts in the human skin development and aging dynamics

The mammalian target of rapamycin (mTOR) pathway is an important cellular signaling pathway involved in a number of important physiological functions, including cell growth, proliferation, metabolism, protein synthesis and autophagy in response to various external stimuli. The mTOR signaling pathway significantly affects the aging process in the body, regulating cellular functions and adaptation to stressful conditions, but its significance for the development and physiological aging of human skin remains poorly understood and opens up prospects for further research. The aim of the study was to study the dynamics of changes in the proportion of mTOR+-fibroblasts in the human dermis during skin development and aging and to determine the possible role of mTOR in regulating the number and proliferative activity of fibroblasts during its age-related changes. The study material included 114 skin preparations from autopsy cases of different ages. The skin samples were autopsies of the lower part of the anterior neck surface obtained from fetuses starting from the 20th week of pregnancy and from humans from birth to 85 years of age. MTOR+-, PCNA+- and vimentin+-fibroblasts were studied on formalin-fixed sections using the immunohistochemical method. The results obtained allow us to conclude that the skin of fetuses contains significantly more mTOR+-fibroblasts than the skin of humans from birth to 85 years of age. The proportion of fibroblasts expressing mTOR in the human dermis statistically significantly decreases from the age of 20 weeks to 60 years from 95% to 78%, which proves the importance of the age factor in the content of mTOR+-fibroblasts in the human dermis. In the postnatal period, a gradual decrease in the proportion of mTOR+-fibroblasts is observed. The negative dynamics of age-related changes in the proportion of mTOR+-fibroblasts in the dermis from the fetal period to 60 years of age is in the same direction as the age-related dynamics of the total number and proliferative activity of fibroblasts. Thus, evidence has been obtained for the age-specificity of mTOR participation in the regulation of fibroblast proliferation in the dermis of human skin.