Visual impairment in elderly people is a serious problem that significantly affects the quality of life of millions people around the world. The magnitude of this problem is becoming increasingly apparent as the population ages and the number of older people increases. Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide and the main cause of vision loss in people over 60 years. It is expected that AMD will affect about 288 million people by 2040. AMD is a multifactorial disease with a progressive course. The arised dystrophic changes in the retina cannot be reversed by any of the known treatment methods. A lot of research and effort has already been invested in identifying various biomarkers for predicting the incidence rate, identifying people at risk, finding out the pathogenetic mechanisms of this disease, and finding effective methods of treatment and prevention.Aging is the basis of pathological changes that occur during AMD. Aging biomarkers are measurable vital signs that qualitatively and quantitatively change with the age of the body. DNA methylation is a molecular mechanism that is a potential biomarker of aging. Sirtuins indirectly participate in this process, regulating the activity of the DNMT1 enzyme. The article discusses current knowledge of the mechanisms underlying the action of sirtuins (Sirtuins / SIRT), with an emphasis on SIRT1. Analysis of the pathophysiological action of sirtuins can affect the prevention and treatment of pathological eye changes associated with AMD. The article provides literature sources containing the results of studies of the effect of SIRT1 as a marker of aging in body tissues. SIRT1 is an attractive candidate for developing therapeutic strategies preventing early eye aging, in particular, age-associated diseases such as AMD The impact on the genetic mechanisms of this disease is a promising direction in treatment.
С момента своего открытия теломеры и теломераза стали предметом множества исследований, сначала как механизм клеточного старения, а затем как индикатор здоровья и заболеваний у людей. Защищая концы хромосом, теломеры играют жизненно важную роль в сохранении информации в нашем геноме. В обзоре приведены результаты ранних исследований, которые в последующем стали основанием для дальнейшего, более глубокого изучения и экспериментов, также представлены исследования, демонстрирующие взаимосвязь укорочения длины теломер с нейродегенеративными заболеваниями, в частности с возрастной макулярной дегенерацией (ВМД). Кроме того, рассмотрены механизмы клеточного старения, вызванные истощением теломер. Понимание молекулярных механизмов, вовлеченных в процесс старения, может выявить новые стратегии лечения и профилактики такого возраст-ассоциированного заболевания, как ВМД. Данная патология является основной причиной потери зрения у пожилых людей после глаукомы и катаракты. ВМД диагностируется на основании характерных патологических изменений сетчатки у лиц старше 50 лет. Распространенность «сухой» и «влажной» форм ВМД варьируется в разных этнических и расовых группах по всему миру. Среди лиц одной возрастной категории можно наблюдать разные формы, распространенность и стадии ВМД. Такое наблюдение подтверждает необходимость поиска биомаркера, способного осуществлять мониторинг за процессом старения, лежащим в основе данной патологии, а также возможных причин различий в течении и исходе заболевания. В обзоре используются литературные источники, отражающие развитие представлений о проблеме.
One of the most important factors predisposing to the development of age-related macular degeneration (AMD) is aging. Telomeres are important for aging by maintaining genome stability. Aim: to identify the association between relative telomere length of buccal epithelial cells and SIRT1 rs12778366 genetic variation and late AMD. Patients and Methods: 100 patients (200 eyes) were enrolled, i.e., 50 patients with AMD (AREDS category 4) and 50 patients without AMD. Genomic DNA isolated from buccal epithelial cells by phenol-chloroform extraction was used. Genotyping of SIRT1 rs12778366 polymorphic locus was performed by TaqMan® real-time PCR. Telomere length was measured by real-time PCR as described earlier [Cawthon, 2002] using specific primers. Relative telomere length was assessed by the relative telomere to single-copy gene (T/S) ratio. Results: the rate of allele C was 25% in the study group and 14% in the control group (p=0.049). The rate of heterozygotic TC genotype was twice higher in the study group compared to the control group (p=0.045). In heterozygotic carriers of the allele C of the SIRT1 rs12778366 gene, the risk of AMD is 2.048- and 2.425-times higher in сodominant and dominant inheritance pattern, respectively. In patients with late AMD, there are more short telomeres (64% vs. 48% in the control group, р=0.0002). Conclusions: further studies of a polymorphic SIRT1 gene locus in the association with telomere length in a larger sample are required. In the future, these molecular markers can be applied to predict the individual course of AMD and to implement preventive measures. Keywords: age-related macular degeneration, relative telomere length, rs12778366, SIRT1 gene, age-related diseases, buccal epithelium, genetic testing. For citation: Moshetova L.K., Dmitrenko O.P., Abramova O.I. et al. Association between relative telomere length and a genetic variant of SIRT gene and age-related macular degeneration. Russian Journal of Clinical Ophthalmology. 2021;21(3):143–146 (in Russ.). DOI: 10.32364/2311- 7729-2021-21-3-143-146.
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