Replicative and biochemical ageing mechanisms among females with Turner syndromes

Abstract

BACKGROUND: 2025 is going to be the 100th anniversary of the first historical description of Turner syndrome — complex of  genomic abnormalities, congenital gonadal disruption and hypergonadotropic hypogonadism. Total estrogenic deficiency triggers development of age-related comorbidities. There is no doubt that personalized search for replicative markers of cellular aging among females with Turner syndrome is needed.AIM: To evaluate features of replicative (telomere length) and biochemical (lipid profile, calcium-phosphate album, thyroid hormones, markers cytolysis and cholestasis, carbohydrate metabolism, nitrogenic metabolism, electrolytes, FSH) markers among females with Turner syndrome.MATERIALS AND METHODS. Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022. Females with non-iatrogenic hypergonadotropic hypogonadism caused by Turner syndrome (45,X0; 45,X/46,XX; 45,X/46,X,r(X); 13–40 y.o.; n=26) and primary ovarian insufficiency (18–39 нyears=26); healthy females of reproductive age (15–49 y.o.; n=24). Patients have undergone laboratory genetic (leucocyte telomere length), biochemical (fasting glycaemia, urea, creatinine, common/conjugated bilirubin, ALT, AST, gamma-glutamyl transferase, triglycerides, HDL-P, LDL-P, common cholesterol, common/ionized calcium, phosphate, vitamin D, sodium/potassium/chlorides, FSH, HbA1c) analyses. Body measurements — body mass, body height. DNA extraction — provided with Qiagen DNA blood mini kit (Germany). Leukocyte telomere length — with real-time polymerase chain reaction PCR (Flow-fish). Soft program IBM SPSS Statistics (version 26,0 for Windows).RESULTS. 1. Females with Turner syndrome have significantly lower mean telomere length (8,22 kB [6,63–9,30]) than with primary ovarian insufficiency (10, 34 кБ [8,41–13,08], p<0,001) and healthy reproductive age females (10,77 kB [9,95–13,16], р>0,05).2. Telomere length correlates directly and significantly with longevity of menopausal hormonal therapy among females with primary ovarian insufficiency (ρ = 505; p<0,001).3. Patients with Turner syndrome are inclined to vitamin D deficiency (р<0,001), dyslipidemia (р=0,01); increase of levels of aminotransferases, cholestasis markers, phosphate and FSH (р<0,001).CONCLUSION. Turner syndrome is serious genetic disease that leads not only to infertility but to significant decrease of quality/life longevity out of “healthy aging” conception.