Изменение экспрессии мРНК панели генов в слизистой оболочке толстой кишки в процессе естественного старения

Abstract

Background: during natural aging, cellular and molecular changes in the colonic mucosa contribute to chronic damage and the development of various neoplasia, including colorectal cancer (CRC). Aim: to assess the age peculiarities of mRNA expression in samples of normal mucosa from various parts of the colon. Patients and Methods: the study included 95 patients. Normal colonic mucosa biopsies were derived during videocolonoscopy from different parts of the colon, i.e., the right colon (n=91), left colon (n=95), and rectum (n=87). In total, 273 samples were examined. The relative level of mRNA expression of 63 genes potentially involved in various pathways of CRC carcino-genesis was evaluated by reverse transcription polymerase chain reaction. Results: a linear regression model for predicting passport age, including data on gene ex-pression, was characterized by moderate reliability (R2 0.45, DW test 1.54). Age estimation er-rors in the model arise proportionally to its increase, which is associated with the accumulation of epigenetic changes. Maximum accuracy in age prediction is typical for rectal mucosa samples. The first statistically significant division (primary classification node) of patients by age in indi-viduals over or under 60 years provides the level of TERT gene expression. Telomerase activity in association with HLA-G5 gene overexpression is typical in older patients, whereas HLA-G5 gene hypoexpression and simultaneous granulysin (GNLY) overexpression are typical in patients younger than 60 years. A molecular cascade involving a decrease in telomerase activity due to TERT hypoexpression with simultaneous overexpression of the cell cycle regulator and tumor suppressor P14ARF is also typical for normal colonic mucosa in patients aged 60 years and over. Conclusion: our findings support molecular genetic changes in the colonic mucosa that occur with age. The specifics of gene expression involved in CRC carcinogenesis are the basis for assessing CRC risk. KEYWORDS: gene expression, mRNA, RT-PCR, normal colon mucosa, age, epigenetic changes, colorectal cancer. FOR CITATION: Goncharov S.V., Bozhenko V.K., Zakharenko M.V., Chaptykov A.A., Kulinich T.M., Solodkiy V.A. Changes in mRNA expression of colon mucosa genes during natural aging. Russian Medical Inquiry. 2023;7(6):347–352 (in Russ.). DOI: 10.32364/2587-6821-2023-7-6-2.