Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences68617010.31857/S0016675825010092VEFHNDГЕНЕТИКА ЧЕЛОВЕКАResearch ArticleAlu polymorphisms of autophagy and apoptosis regulatory genes as human lifespan factorsAlu-полиморфизм генов-регуляторов аутофагии и апоптоза как фактор продолжительности жизни человекаErdmanV. V.ЭрдманВ. В.
Russian Federation
danivera@mail.ruKarimovD. D.КаримовД. Д.
Russian Federation
danivera@mail.ruTuktarovaI. А.ТуктароваИ. А.
Russian Federation
danivera@mail.ruPetintsevaA. A.ПетинцеваА. А.
Russian Federation
danivera@mail.ruTimashevaY. R.ТимашеваЯ. Р.
Russian Federation
danivera@mail.ruNasibullinT. R.НасибуллинТ. Р.
Russian Federation
danivera@mail.ruInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукBashkir State Medical UniversityБашкирский государственный медицинский университетUfa Research Institute of Occupational Medicine and Human EcologyУфимский научно-исследовательский институт медицины труда и экологии человека150120256119110227062025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/686170

To assess the contribution to survival of Alu-insertions in the ACE, PLAT, COL13A1, LAMA2, CDH4, SEMA6A, PKHD1L1, STK38L, HECW1, TEAD1 genes, which are candidates of aging and longevity, amid the senile physiological and pathological phenotype, was carried out the association analysis with life expectancy. Survival and mortality data were obtained for 1,382 elderly people, who were selected from the sample of Tatars residing in the Republic of Bashkortostan (total 1790 people from 18 to 109 years). Mortality risk was higher among carriers of the STK38L Alu-insertion genotype (Ya5ac2145*II, HR = 2.07, P = 0.02). Alu-insertion in the HECW1 and TEAD1 genes has demonstrated a survival protection effect (Ya5NBC182*II, HR = 0.71, P = 0.038 and Ya5ac2013*II, HR = 0.74, P = 0.035 respectively). The survival amid the persons with various clinical phenotypes was associated with the Alu polymorphism of the SEMA6A (Yb8NBC597*ID, HR = 0.54, P = 0.016 for the cerebrovascular diseases), TEAD1 (Ya5ac2013*II, HR = 0.57, P = 0.016 for the cardiovascular pathologies) and LAMA2 (Ya5-MLS19*ID, HR = 0.36, P = 0.03 for multimorbidity status) genes. Thus, the genes involved in the regulation of autophagy and apoptosis were associated with survival and longevity.

Для оценки вклада Alu-инсерций в генах-кандидатах старения и долголетия ACE, PLAT, COL13A1, LAMA2, CDH4, SEMA6A, PKHD1L1, STK38L, HECW1, TEAD1 в выживаемость на фоне старческого физиологического и патологического фенотипа проведен анализ ассоциаций с продолжительностью жизни. Получены данные о причинах смерти 1382 человек преклонного возраста из выборки татар, проживающих в Республике Башкортостан (всего 1790 человек от 18 до 109 лет). Риск смерти оказался повышен у лиц с Alu-инсерцией в гене STK38L (Ya5ac2145*II, HR = 2.07, P = 0.022). Alu-инсерционные варианты генов HECW1 и TEAD1 продемонстрировали протективный в отношении выживаемости эффект (Ya5NBC182*II, HR = 0.71, P = 0.038 и Ya5ac2013*II, HR = 0.74, P = 0.035 соответственно). С выживаемостью при различных клинических фенотипах ассоциированы Alu-полиморфные варианты генов SEMA6A (Yb8NBC597*ID, HR = 0.54, P = 0.016 при цереброваскулярных заболеваниях), TEAD1 (Ya5ac2013*II, HR = 0.57, P = 0.016 при сердечно-сосудистых патологиях) и LAMA2 (Ya5-MLS19*ID, HR = 0.36, P = 0.03 при полиморбидности). Таким образом, с выживаемостью и достижением долголетия оказались ассоциированы гены, вовлеченные в регуляцию аутофагии и апоптоза.

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