After cholecystectomy, elderly patients require special attention, due to the influence of involution processes in the body on the formation of complications. To identify prognostic criteria for the formation of fatty liver degeneration in the long-term period of minimally invasive cholecystectomy, 159 men were examined. Dysregulation of the biliary tract was determined using magnetic resonance cholangiopancreatography, elastography and magnetic resonance imaging of the liver. Microbial markers of the wall microbiome of the intestine were determined using chromatography-mass spectrometry. The relationship between an increase in body mass index and a decrease in the amount of obligate microbiome (r=-0,43, p<0,050), as well as with the formation of fatty liver degeneration in elderly patients, was revealed. The features of vegetative regulation in elderly people with fatty liver degeneration have been determined. It has been proven that in old age, a decrease in the number of obligate anaerobic association of microorganisms of the small intestine (on average from 15 659 to 7 630 in persons of the 2nd age subgroup and from 1 457 to 17 837 in the 3rd) is a predictor of fatty liver degeneration. The prognostic algorithm developed on the basis of the analysis of highly informative signs makes it possible to identify with an accuracy of at least 75% a high risk of fatty liver degeneration in the long-term period of cholecystectomy.
Исследование заключалось в определении влияния стентирования почечных артерий у пациентов с артериальной гипертензией в сочетании со стенозом почечных артерий на клинико-гериатрический статус по таким показателям, как число принимаемых препаратов, когнитивный статус, определяемый по шкале MMSE, распространенность частоты падений, психоэмоциональный статус по шкале Бека, качество сна по шкале ВАШ, индекс возрастной дискриминированности по опроснику эйджизма E. Palmore, качество жизни по опроснику SF-36. В исследовании приняли участие 72 пациента пожилого возраста с артериальной гипертензией в сочетании со стенозом почечных артерий. По итогам проведенного исследования, в результате стентирования почечных артерий отмечается уменьшение числа принимаемых препаратов, улучшение когнитивного статуса по шкале MMSE, уменьшение распространенности частоты падений, улучшение психоэмоционального статуса по шкале Бека и качества сна по шкале ВАШ, снижение уровня возрастной дискриминированности, повышение качества жизни по всем шкалам опросника SF-36. The study consists in determining the effect of renal artery stenting in patients with arterial hypertension in combination with renal artery stenosis on the dynamics of clinical and geriatric status in terms of such indicators as the number of drugs taken, cognitive status, determined by the MMSE scale, prevalence of the frequency of falls, psycho-emotional status by the Beck scale, the quality of sleep on the VAS scale, the index of age discrimination according to the E. Palmore ageism questionnaire, the quality of life according to the SF 36 questionnaire. The study involved 72 elderly patients with arterial hypertension in combination with renal artery stenosis. According to the results of the study, as a result of stenting of the renal arteries, there is a decrease in the number of drugs taken, an improvement in the cognitive status on the MMSE scale, a decrease in the frequency of falls, an improvement in the psycho-emotional status on the Beck scale, an improvement in the quality of sleep on the VAS scale, a decrease in the level of age discrimination, an increase in the quality of life according to questionnaire SF-36 on all scales.
Перед началом клинических испытаний стентов обязательным является этап испытания их на животных. Именно кролики лучше всего подходят для этих целей, так как их артерии схожи с человеческими по реакции сосудистой стенки на стент. Установка артериальных имплантатов в брюшную аорту кролика с доступом к сосудам через сонную артерию представляет собой недорогую и удобную экспериментальную модель in vivo для проведения доклинических испытаний эндоваскулярных имплантатов (в частности, коронарных стентов), рассмотрения влияния новых моделей. Первые опыты на кроликах в области рентгенохирургии сосудов и сердца проводились уже в начале XX века. Техники оперативного вмешательства не требуют специализированного инструментария: используются стандартные медицинские изделия для проведения эндоваскулярных вмешательств (интродьюсеры, проводники, индефляторы, диагностические катетеры). Before starting clinical trials of stents, the stage of testing them on animals is mandatory. It is rabbits that are best suited for these purposes, since their arteries are similar to the human reaction of the vascular wall to the stent. Installation of arterial implants in the abdominal aorta of a rabbit with access to vessels through the carotid artery is an inexpensive and convenient experimental model in vivo for preclinical testing of endovascular implants, in particular coronary stents, to consider the impact of new models. The first experiments on rabbits in the field of X-ray surgery of blood vessels and the heart were already at the beginning of the 20th century. Surgical intervention techniques do not require specialized instruments: standard medical devices for endovascular interventions (introducers, conductors, inflators, diagnostic catheters) are used.
The sirtuin family of proteins (SIRT proteins) are involved in DNA repair, chromatin remodeling, epigenetic regulation of the expression of metabolism genes, the antioxidant system, apoptosis, immuno- and neurogenesis, etc. The aim of this review is to analyze the geroprotective properties of sirtuins in normal and age-associated pathologies. SIRT1, 2, 3, 4, and 6 contribute to increases in life expectancy. SIRT1, 2, 6, and 7 slow cellular aging and maintain the stem cell pool. Sirtuins are potential targets for the treatment of neurodegenerative, oncological, and cardiovascular diseases, metabolic syndrome, and diabetes mellitus. All these diseases are in most cases characteristic of elderly and old people, so the geroprotective effects of sirtuins, realized at the molecular and cellular levels, may play an important role in the treatment of these conditions.
Background . One of the factors of the pathogenesis of atherosclerosis and other cardiovascular diseases is induced endothelial senescence. In this regard, the urgent task of molecular biology and medicine is the search for molecules that affect the process of vascular endotheliocytes senescence. The aim . To assess the expression of Sirt-1,3,6 and chemokines IL-4, CXCL11 in the replicative and induced senescence of human endotheliocytes. Materials and methods . The study was conducted on the primary culture of isolated human umbilical vein endothelial cells (HUVECs). HUVECs were cultured under conditions of replicative (natural) and lipopolysaccharide induced senescence. Results . The synthesis of Sirt-1,3,6, IL-4 and CXCL11 was evaluated using western blot analysis. We revealed a decrease in Sirt-1,3,6 synthesis by 1.6–1.8 times (р < 0.05) in the conditions of HUVEC replicative senescence. Induced senescence of endotheliocytes is characterized by a more pronounced decrease (1.7–3.4 times; р < 0.05) in the Sirt-1,3,6 synthesis. CXCL11 synthesis increases by 1.4 times (р < 0.05) in replicative and by 3.4 times (р < 0.05) in induced HUVEC senescence. IL-4 synthesis increases by 4.7 times in conditions of induced HUVEC senescence and doesn’t have changes in replicative senescence of endotheliocytes. Conclusion . These data obtained indicate that sirtuins and chemokines play an important role in the development of endothelial dysfunction observed in natural and induced senescence.
У большинства пациентов старше 50 лет диагностируют заболевания зубочелюстного аппарата, в частности нарушения костной ткани, что приводит к снижению процента приживаемости имплантов. Выявление причин, а также разработка методики прогнозирования приживаемости малоинвазивными методами являются актуальными проблемами. Цель исследования - изучение маркеров плотных контактов в буккальном эпителии у людей разного возраста. Соскоб буккального эпителия брали до и после имплантации у пациентов, разделенных на пять возрастных групп - от молодого возраста до долгожителей. Иммуноцитохимическим методом изучали маркеры к белкам плотных контактов - клаудину-1, -7 и -10. Показано, что с возрастом происходит снижение интенсивности экспрессии молекул адгезии, в частности клаудина -1, -7 и -10, в слизистых оболочках, минимальные значения зафиксированы в группе долгожителей. В исследовании установлено, что после дентальной имплантации снижается экспрессия клаудинов-1 и -10 и увеличивается - клаудина-7. Изменение экспрессии клаудинов может свидетельствовать о развитии патологического процесса в организме, в том числе об успехе имплантации, особенно у людей старших возрастных групп. Most patients over 50 years of age are diagnosed with diseases of the dentoalveolar apparatus, in particular, bone tissue disorders, which leads to a decrease in the survival rate of implants. Identification of the causes, as well as the development of a methodology for predicting survival by minimally invasive methods, is relevant. The aim of the study was to study the markers of tight junctions in the buccal epithelium (BE) in people of different ages. BE scrapings were taken before and after implantation in patients divided into 5 age groups, from young to centenarians. Immunocytochemical method was used to study markers for tight junction proteins - claudin-1, -7 and 10. It has been shown that with age there is a decrease in the intensity of expression of adhesion molecules, in particular claudin -1, -7 and -10 in the mucous membranes, the minimum values were recorded in the group of centenarians. The study found that after dental implantation, there was a decrease in the expression of claudin-1 and -10 and an increase in the expression of claudin-7. Changes in the expression of claudins may indicate the development of a pathological process in the body, including the success of implantation, especially in people of older age groups.
Секреторный фенотип, ассоциированный со старением (SASP), - гетерогенный фенотип клеток, секретирующих провоспалительные цитокины, факторы роста, апоптоза и протеазы. SASP является одним из трех основных признаков стареющих клеток. Нарушение регуляции синтеза молекул, формирующих SASP, приводит к развитию ассоциированных с возрастом заболеваний, в том числе сердечно-сосудистой патологии. Цель исследования - охарактеризовать SASP эндотелиоцитов человека при репликативном и индуцированном старении. Для моделирования репликативного и вызванного воспалением старения использовали линию изолированных эндотелиальных клеток пупочной вены человека HUVEC. Установлено, что молекулами, формирующими SASP при репликативном и индуцированном воспалением старении HUVEC, являются факторы апоптоза (p16, p21, p53), адгезии (Е-селектин, VCAM-1) и цитокины (IL-1β, IL- 6). При репликативном старении эндотелиоцитов в большей степени повышается синтез молекул апоптоза. Для индуцированного воспалением старения HUVEC характерно многократное увеличение синтеза молекул адгезии и провоспалительных цитокинов. The aging-associated secretory phenotype (SASP) is a heterogeneous phenotype of cells secreting pro-inflammatory cytokines, growth factors, apoptosis’ regulatory molecules, and proteases. SASP is one of the three main hallmarks of senescent cells. Dysregulation of the synthesis of SASP-forming molecules leads to the development of age-associated diseases, including cardiovascular pathology. The aim of this study is to characterize the SASP of human endotheliocytes during replicative and induced aging. Isolated human umbilical vein endothelial cells HUVEC were used to model replicative and inflammation-induced aging. It has been established that the molecules that form SASP during replicative and inflammation-induced aging of HUVEC are molecules that control apoptosis (p16, p21, p53), adhesion (E-selectin, VCAM-1) and some cytokines (IL-1β, IL-6). With replicative aging of endotheliocytes, the synthesis of apoptosis’ regulatory molecules increases to a greater extent. Inflammation-induced aging of HUVEC is characterized by a multiple increase in the synthesis of adhesion molecules and pro-inflammatory cytokines.
Самым распространенным пороком клапанов сердца у лиц пожилого и старческого возраста является стеноз аортального клапана. Традиционным методом лечения тяжелого аортального стеноза (АС) считается открытая операция по замене аортального клапана. Более современным малоинвазивным методом коррекции АС является транскатетерная имплантация аортального клапана (TAVI). Данное вмешательство прежде всего показано пациентам старческого возраста и высокого хирургического риска, страдающим тяжелой ХСН, обусловленной АС. В настоящее время TAVI превратилась из сложной и опасной процедуры в эффективный и безопасный метод лечения благодаря разработке устройств нового поколения. При этом актуальными остаются вопросы использования TAVI в отдельных клинических случаях: применение TAVI в пожилом возрасте (60-75 лет), TAVI у долгожителей (90 лет и более), TAVI при старческой астении (frailty), целесообразность TAVI при низком хирургическом риске и другие, а также вопросы, связанные с долговечностью клапанов, применяемых для TAVI, и прогнозом в отношении качества и продолжительности жизни. The most common heart valve defect among the elderly and senile is aortic valve stenosis. The traditional method of treating severe aortic valve stenosis is open surgery to replace aortic valve. At the same time, a more modern, minimally invasive method of correcting aortic stenosis is transcatheter aortic valve implantation (TAVI). This intervention is primarily indicated for patients of old age suffering from severe chronic heart failure associated with aortic stenosis, who have a high surgical risk. Currently, TAVI has evolved from a complex and dangerous procedure into an effective and safe method of treatment thanks to the development of a new generation of devices. Currently, there are still topical issues of using TAVI in individual clinical cases (use of TAVI in the elderly (60-75 years), TAVI in centenarians (90 years or more), TAVI in frailty, the feasibility of performing TAVI with low surgical risk, etc.), as well as issues related to longevity valves used for TAVI and prognosis in terms of quality and life expectancy.
To understand the pathogenesis of dilated cardiomyopathy (DCMP), it is necessary to establish the molecular and cellular mechanisms of myocardial aging, including those associated with programmed cell death, the molecular mechanisms of which have not been extensively studied. The aim of this work is to study markers of apoptosis in cardiomyocytes of patients with DCMP in vitro. We used the method of primary dissociated cell cultures and the method of immunofluorescence confocal laser microscopy. Cells of the 3rd and 14th passages, corresponding to “young” and “old” cultures, were used to simulate cellular senescence. At the molecular level, aging of cardiomyocyte cells was accompanied by a twofold increase in the expression of p16INK4a compared to “young” cultures, both in the control group and in the group with DCMP. It was also found that the expression of p16INK4a in cultures taken from patients with pathology was two times higher than in similar cultures from healthy patients. The expression of p21 was increased in the group with DCMP compared to the control; however, with aging of the culture, the expression of p21 did not change, remaining at a significant level. The most significant (3.2-fold) differences were obtained when comparing the expression of Bax in the cell culture of cardiomyocytes from the group with DCMP in the “young” culture compared with the control. Aging of myocardial cells at the molecular level was manifested in an increase in the expression of the Bax protein, which is the triggering mechanism of the mitochondrial apoptosis pathway. It is possible that this pathway of cell death is prevalent in DCMP.
Актуальность. В патогенезе дилатационной кардиомиопатии (ДКМП) у лиц старших возрастных групп важную роль играет инфламэйджинг и нарушение мелатонинобразующей функции эпифиза. Важной задачей молекулярной медицины является поиск сигнальных молекул - маркеров ДКМП. Цель работы - провести сравнительную оценку концентрации IL-1β, IL-6, Klotho, Sirt3, FGF23 и мелатонина в слюне у пациентов старших возрастных групп с ДКМП и без неё. Методы. Определение концентрации сигнальных молекул в слюне осуществляли методом иммуноферментного анализа с последующей статистической обработкой полученных данных. Результаты. У пациентов с ДКМП пожилого и старческого возраста концентрация маркеров инфламэйджинга (IL-1β, IL-6) в слюне повышалась в 8,6-19,1 раза по сравнению с этими показателями у лиц без ДКМП. Концентрация белка Klotho, ингибирующего синтез провоспалительных цитокинов, в слюне пациентов с ДКМП пожилого и старческого возраста была в 4,2-7,6 раза ниже по сравнению с этим показателем у лиц без ДКМП. У пациентов с ДКМП пожилого и старческого возраста концентрация в слюне мелатонина и регулируемого им Sirt3 была в 2,1-4,3 раза ниже по сравнению с этим показателем у лиц без ДКМП. Концентрация FGF23 в слюне не зависела от возраста пациентов и наличия ДКМП. Заключение. В патогенезе ДКМП у лиц старших возрастных групп важную роль играет инфламэйджинг. Об этом свидетельствует снижение синтеза белка Klotho и повышение уровня провоспалительных цитокинов IL-1β и IL-6. Другим звеном патогенеза ДКМП является снижение синтеза мелатонина и, как следствие, нарушение функции сигнального пути Mst1/Sirt3. Исследование концентрации IL-1β, IL-6, Klotho, SIRT3 и мелатонина в слюне может применяться для молекулярной диагностики ДКМП у лиц пожилого и старческого возраста. Background. Inflammaging and disorder of melatonin synthesis in the pineal gland play an important role in the pathogenesis of dilated cardiomyopathy (DC) in elderly and old people. An important objective of molecular medicine is searching for signal molecules, markers of DC. The aim of this work was to compare concentrations of IL-1β, IL-6, Klotho, Sirt3, FGF23, and melatonin in saliva of elderly and old DC patients and persons without DC. Methods. Concentrations of signal molecules were measured in saliva by ELISA. Results. Salivary concentrations of inflammaging markers (IL-1β, IL-6) in elderly and old DC patients were 8.6-19.1 times higher than in persons without DC. Salivary concentration of Klotho protein, an inhibitor of pro-inflammatory cytokine synthesis, was increased 4.2-7.6 times in elderly and old DC patients compared to the values in persons without DC. Salivary concentrations of melatonin and melatonin-regulated Sirt3 were decreased 2.1-4.3 times in elderly and old DC patients compared to the values in persons without DC. Salivary concentration of FGF23 did not depend on the age or presence of DC. Conclusion. Inflammaging plays in important role in the pathogenesis of DC in elderly and old people as evidenced by decreased synthesis of Klotho and increased levels of the pro-inflammatory cytokines IL-1β and IL-6. Another step in the DC pathogenesis is decreased melatonin synthesis and the resultant dysregulation of the Mst1/Sirt3 signaling way. Measuring concentrations of IL-1β, IL-6, Klotho, SIRT3, and melatonin in saliva can be used for molecular diagnostics of DC in elderly and old people.
At this moment differential diagnostic of the prostate cancer (PC) needs the new, more effective ways with regard of multifactor analysis. One of this factor is patient's age. Men older than 45 years old have expressed involution changes of prostate tissues. This fact must be take into account in valuation morphologic and laboratory criteria's in PC. The goal of the investigation is to take into account age-related changes of the prostate volume and laboratory criteria of blood analysis in PC. 632 patients in age from 42 to 88 years old were exanimated by trans rectal ultrasound examination (TRUS) method (volume parameters of the prostate) and by levels of prostate-specific antigen (PSA) and (-2) pro-PSA in blood. The increase of patient's age correlated with increase of the density of transient, peripheral and central zones of prostate. It correlates with the probability of the frequency of PC verification. Levels of PSA and 2-pro-PSA in blood of PC patients increase during the transition from middle to elderly age in 1,4-2,8 times. Thus the information, which was obtained during the examination of volume prostate characteristics by TRUS method and laboratory diagnostic of PC, must take to account patient's age.
Sirtuins (SIRT) are a class of NAD-dependent proteins with deacetylase activity that are involved in the regulation of transcription, metabolic pathways, and cell aging via the deacetylation of histone and nonhistone targets. It was hypothesized that sirtuins play important role in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD). An age-related decrease in sirtuin expression leads to oxidative stress, which can cause neurodegeneration. This article examines the age-related dynamics of SIRT1, 3, 5, and 6 expression in patients with AD and in healthy individuals with immunohistochemistry and immunocytochemistry methods via immunofluorescent confocal microscopy. In elderly and senile health individuals, the SIRT1, 3, 5, and 6 expression in the hippocampus and buccal epithelium did not differ significantly. In AD patients, the SIRT1, 3, 5, and 6 expression in the hippocampus and buccal epithelium decrease by 1.5–5 times as compared with healthy elderly and senile individuals. The SIRT5 expression in the hippocampus and buccal epithelium does not depend on the age or AD diagnosis. Thus, the SIRT 1, 3, and 6 expression in the buccal epithelium can be a marker for intravital, noninvasive AD diagnosis in elderly and senile individuals.
Background. Inflammaging and disorder of melatonin synthesis in the pineal gland play an important role in the pathogenesis of dilated cardiomyopathy (DC) in elderly and old people. An important objective of molecular medicine is searching for signal molecules, markers of DC.The aim of this work was to compare concentrations of IL-1β, IL-6, Klotho, Sirt3, FGF23, and melatonin in saliva of elderly and old DC patients and persons without DC.Methods. Concentrations of signal molecules were measured in saliva by ELISA.Results. Salivary concentrations of inflammaging markers (IL-1β, IL-6) in elderly and old DC patients were 8.6-19.1 times higher than in persons without DC. Salivary concentration of Klotho protein, an inhibitor of pro-inflammatory cytokine synthesis, was increased 4.2-7.6 times in elderly and old DC patients compared to the values in persons without DC. Salivary concentrations of melatonin and melatonin-regulated Sirt3 were decreased 2.1-4.3 times in elderly and old DC patients compared to the values in persons without DC. Salivary concentration of FGF23 did not depend on the age or presence of DC.Conclusion. Inflammaging plays in important role in the pathogenesis of DC in elderly and old people as evidenced by decreased synthesis of Klotho and increased levels of the pro-inflammatory cytokines IL-1β and IL-6. Another step in the DC pathogenesis is decreased melatonin synthesis and the resultant dysregulation of the Mst1/Sirt3 signaling way. Measuring concentrations of IL-1β, IL-6, Klotho, SIRT3, and melatonin in saliva can be used for molecular diagnostics of DC in elderly and old people.
The differential diagnostic of prostate cancer is the actual task of modern medicine. The existing methods lack accuracy and specificity. It’s the reason of hyper- or hypo-diagnostic of this disease. We developed and tested the new logistic regression model for diagnostic of prostate cancer in men of various age. The model includes age, the volume of prostate, concentration of prostate specific antigen (PCA), 2-pro-PCA in the blood, the presence of the concretion revealed during digital rectal investigation of prostate and hypoechogenic area in transrectal ultrasound investigation. The model was tested in 114 patients. It has shown the higher accuracy and specificity of the new regression model in comparison to other methods of differential diagnostic of prostate cancer.
Insufficient knowledge age peculiarities of the clinical course of cardiac arrhythmias occurring asymptomatically as a manifestation of cardiotoxicity in women with breast cancer at the stage of radiation therapy, determines the high demand for research on this problem. The aim of the study was to identify and evaluate asymptomatic cardiac arrhythmias in elderly women with left breast cancer at the stage of radiation therapy. 48 women without a history of severe cardiovascular disease with HER2neu negative cancer of the left breast at the stage of 3D conformal radiotherapy were examined. Mean age 67 (64; 69). All patients at the previous stages were carried out mastectomy Madden followed by therapy with doxorubicin. The examination included ECG registration, 24-hour ECG monitoring and echocardiography. Before radiation therapy, asymptomatic arrhythmias were detected in 43 (89,6%) patients. After radiation therapy significantly increased the number of pathological supraventricular and ventricular arrhythmias as a manifestation of cardiotoxicity.
Verification of signaling molecules in the saliva is a non-invasive method of diagnosis and evaluation of treatment effectiveness in different pathologies. Sirtuins (SIRT), proteins from NAD-dependent histone deacetylases, are supposed to be involved in the pathogenesis of Alzheimerэs disease. Age-related decrease in sirtuins expression induces many pathophysiological processes that could lead to neurodegeneration. We studied the expression of SIRT1, SIRT3, SIRT5, and SIRT6 in the hippocampus and saliva of humans without neurological pathologies and in patients with Alzheimer’s disease of elderly and senile age. In elderly and senile patients, the expression of SIRT1, SIRT3, and SIRT6 in the hippocampus and saliva was 1.5-4.9-fold reduced in comparison with healthy individuals of the corresponding age. In healthy senile persons, the expression of SIRT6 in the hippocampus and saliva was 2.5-4.5-fold lower than in healthy elderly individuals. Measurement of SIRT1, SIRT3, and SIRT6 concentration in the saliva can be used as an additional method for intravital non-invasive diagnosis of Alzheimer’s disease in patients of advanced age. SIRT6 concentration in the saliva can be recommended as a marker for assessment of the rate of aging.