{"title":"Should We Consider Water and Antibiotics to Be Geroprotectors?","authors":"A. N. Khokhlov, G. V. Morgunova","doi":"10.1134/S2079057024600460","DOIUrl":"10.1134/S2079057024600460","url":null,"abstract":"<p>The authors try to consider the current situation with experimental gerontological research aimed at finding means to slow down aging and prolong life (geroprotectors/anti-aging drugs). The importance of correct defining aging as a set of age-related changes in the body, leading to an increase in the probability of its death, is emphasized, as well as the importance of attention to which lifespan (average, maximum, median, species-specific) changes under the influence of geroprotectors. It is noted that prolonging the life of non-aging animals with an exponential survival curve can hardly be considered a geroprotective effect. It is emphasized that the rate of aging and lifespan are not always strictly related, so the impact on one of these two indicators does not necessarily affect the second. The methodological aspects of works devoted to the study of the influence of diet restriction/modification on aging and lifespan are analyzed. The need for correct selection of a control group of animals in experimental gerontological studies is noted. According to the authors, such animals should not have any pathologies or genetic defects in order to exclude the possible influence of the studied factors on such abnormalities, and not on the aging process per se. In this regard, the authors do not consider antibiotics or drugs/vaccines against COVID-19 to be geroprotective, although the former led to the most significant increase of average lifespan in the 20th century, and the latter offset its decline in recent years caused by this infection. It is noted that the current situation in experimental gerontology makes it very desirable to have a thorough discussion on the question of what can still be considered geroprotectors/anti-aging drugs. It is proposed to organize such a discussion in the journal <i>Advances in Gerontology</i>.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141504380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Zh. Fursova, A. S. Derbeneva, M. A. Vasilyeva, I. F. Nikulich, M. S. Tarasov, Yu. A. Gamza, N. V. Chubar, O. G. Gusarevich, E. I. Dmitrieva, D. V. Telegina, O. S. Kozhevnikova
{"title":"Current Data on the Age-Related Macular Degeneration Pathophysiology: Focus on Growth Factors and Neurotrophins","authors":"A. Zh. Fursova, A. S. Derbeneva, M. A. Vasilyeva, I. F. Nikulich, M. S. Tarasov, Yu. A. Gamza, N. V. Chubar, O. G. Gusarevich, E. I. Dmitrieva, D. V. Telegina, O. S. Kozhevnikova","doi":"10.1134/S2079057024600162","DOIUrl":"10.1134/S2079057024600162","url":null,"abstract":"<p>Age is a main risk factor for age-related macular degeneration (AMD), a complex multifactorial neurodegenerative retinal disease that is becoming the leading cause of vision loss in people over 55 years in developed countries. The risk of developing and rate of progression of AMD, as well as response to therapy, depend on the interaction of multiple genetic and environmental factors. In advanced stage, AMD is classified into dry atrophic (dry) or neovascular (wet) form. Intravitreal injection of anti-vascular endothelial growth factor agents is currently the first-line therapy for neovascular AMD. Unfortunately, therapy for dry AMD is still challenging, owing to an insufficient knowledge of the exact pathogenetic mechanisms. Considering the heterogeneity of AMD and the complexity of influencing age-dependent physiological processes, aging and immune disorders, the most realistic seems to be the further development of antiangiogenic therapy with an expansion of the range of targets, prolongation of their action and improvement of the delivery system. The neuroprotective potential of exogenous neurotrophins for retinal neurons has been proven; however, in order to develop effective drugs for the dry form of AMD based on them, it is necessary to resolve the issue of ways to effectively deliver them to the retina. In this review we discuss the current data on the AMD pathophysiology with focus on the role of vascular growth factors and neurotrophins.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. N. Dudinskaya, O. N. Tkacheva, I. D. Strazhesko, N. V. Brailova, N. V. Sharashkina
{"title":"Vascular Aging and Telomere Biology: On the Role of Vitamin D3 Deficiency","authors":"E. N. Dudinskaya, O. N. Tkacheva, I. D. Strazhesko, N. V. Brailova, N. V. Sharashkina","doi":"10.1134/S2079057024600368","DOIUrl":"10.1134/S2079057024600368","url":null,"abstract":"<p>The impact of vitamin D3 deficiency on the risk and prognosis of numerous chronic diseases has been actively studied for years. Recent research demonstrates that vitamin D is not merely involved in controlling calcium– phosphorus metabolism, but can also enhance insulin sensitivity, and decrease the incidence of type-2 diabetes mellitus (T2DM), obesity, and the autoimmune destruction of pancreatic β cells. The influence of vitamin D3 on some cardiometabolic risk factors and cardiovascular disease (CVD) is described. Thus, it seems quite relevant to study the role of vitamin D3 in the development of arterial-wall changes in the case of T2DM and insulin resistance (IR) and their relationship with the biology of telomeres. The study is aimed at investigating the relationship between vitamin D3 deficiency and vascular-wall condition by the telomere biology in patients with varying insulin sensitivity. The cross-sectional study involves 305 patients (106 men and 199 women) aged 51.5 ± 13.3 SU. All patients undergo laboratory and instrumental tests; the morphofunctional state of the vascular wall is studied. The telomere length and telomerase activity are determined using polymerase chain reaction. Altogether 18 out of 248 patients (7.2%) are found to have normal vitamin D3 levels (above 30 ng/mL). Vitamin D3 insufficiency or deficiency is determined in 92.8% of subjects. The increase in the vitamin D3 deficiency is accompanied by an increased level of fasting glucose, HbA1c and its elevated concentration, HOMA index, glucose disorders up to T2DM, and higher vascular stiffness. Telomerase activity in the group with vitamin D3 deficiency is significantly lower than in the groups with vitamin D3 insufficiency and normal concentrations. Multiple linear regression analysis shows that they are independently associated with vitamin D3 in T2DM (B = 1.43; st. OR 0.106; <i>p</i> = 0.0001), vascular stiffness (B = 0.075; st. OR 2.11; <i>p</i> = 0.017), fasting glucose (B = 0.169; st. OR 1.62; <i>p</i> = 0.004), HbA1c level (B = 0.062; st. OR 7.4; <i>p</i> = 0.001) and the presence of “short” telomeres (B = 0.09; st. OR 1.154; <i>p</i> = 0.001). Receiver-operating characteristic (ROC) analysis reveals relationships between the BMI (0.634, <i>p</i> = 0.001), duration of T2DM (0.651, <i>p</i> = 0.022), high intima-media thickness (0.614, <i>p</i> = 0.004), vascular stiffness (0.605, <i>p</i> < 0.001), HbA1c (0.588, <i>p</i> = 0.022), and the presence of vitamin D3 deficiency. In persons with varying insulin sensitivity, from insulin resistance to T2DM, it is advisable to assess the vitamin D3 levels for effective prevention of arterial-wall changes in addition to traditional CVD risk factors. Vitamin D3 deficiency requires the active prevention of metabolic disorders and vascular changes.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Demographic Indicators of Probability Models","authors":"G. A. Shilovsky, A. V. Seliverstov","doi":"10.1134/S2079057024600307","DOIUrl":"10.1134/S2079057024600307","url":null,"abstract":"<p>Describing mortality dynamics using average indicators without considering variability can yield average results, impeding the analysis of survival-curve patterns during periods of significant mortality spikes, especially at the oldest or youngest ages. Therefore, instead of the generally accepted Gompertz method, other methods are increasingly used, which rely on comparisons of various demographic indicators. In humans, chronic phenoptosis, in contrast to age-independent acute phenoptosis, manifests as a rectangularization of the survival curve with a simultaneous increase in the life expectancy at birth due to the advancement of social, scientific, and technological progress. Rectangularization is difficult to notice solely by examining the optimal coefficients in the Gompertz—Makeham equation, primarily because of the inevitable calculation errors. This can be avoided by calculating demographic indicators based on the spread of the life expectancy: Keyfitz entropy, Gini coefficient, and coefficient of variation of lifespan. We examine several sub-Gompertzian models of mortality growth with age, which describe the aging of nematodes and insects. Within the sub-Gompertzian model of aging, the increase in mortality with age in invertebrates is quantified as a rectangularization of the survival function estimated by these demographic indicators. On the other hand, the increasing rectangularization of the survival function with the development of scientific and technological progress, demonstrated by a decrease in the Keyfitz entropy, along with a simultaneous increase in the life expectancy in humans, also aligns well with the hypothesis of an age-dependent increase in mortality in mammals overall. Calculations on aging models demonstrate the effectiveness of using Keyfitz entropy and the Gini coefficient as important demographic indicators. The use of these indicators seems preferable, especially for nematodes, where the sub-Gompertzian model of aging is applicable, and for vertebrates, primarily mammals, with certain restrictions, the Gompertz–Makeham law is applicable. Approaches that consider dynamic age-related shifts in improved survival, such as studying imbalances in lifespan, enhance our understanding of the mechanisms of aging. This, in turn, will contribute to the development of more accurate methods for assessing the effects of biologically active substances used in gerontology, such as anti-aging drugs and geroprotectors.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Age-Related Changes and Loss of Damage Resistance of Kidney Tissue: The Role of a Decrease in the Number of Kidney Resident Progenitor Cells","authors":"M. I. Buyan, N. V. Andrianova, E. Yu. Plotnikov","doi":"10.1134/S2079057024600344","DOIUrl":"10.1134/S2079057024600344","url":null,"abstract":"<p>Many organs undergo negative changes during aging that affect their functions and ability to regenerate. In particular, the kidneys become more susceptible to acute injury and are more likely to develop chronic kidney disease with age. One of the reasons for this may be a decrease in the number of resident renal progenitor cells. This review addresses age-related changes that occur in the kidneys at the histological and molecular levels, including those related to the cell cycle, mitochondrial function, oxidative stress, and chronic inflammation. We described the available studies on resident renal stem cells, their niches, morphology, possible markers, and the dynamics of their numbers during the aging process. The reasons for the age-related decline in renal regenerative potential are considered based on molecular and cellular mechanisms.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140589533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Kynurenine Pathway Metabolites in the Development of Frailty in Older Adults","authors":"V. S. Pykhtina","doi":"10.1134/S2079057024600216","DOIUrl":"10.1134/S2079057024600216","url":null,"abstract":"<p>Frailty is the main geriatric syndrome, which is closely associated with age-related diseases and aging in general. Being considered the main pathogenetic mechanism of aging, low-grade chronic inflammation potentially contributes to increased degradation of the essential amino acid tryptophan through the kynurenine pathway. Active metabolites of the kynurenine pathway, when accumulated, implement their immunomodulatory, pro-inflammatory and cytotoxic properties, thereby supporting and enhancing the aging process. Over the past decade, data have been collected on the role of an unbalanced kynurenine pathway in the pathogenesis of frailty and age-related diseases. This review summarizes clinical and experimental data on the importance of kynurenine pathway analysis as a valuable tool for risk stratification and prognosis of frailty and age-related diseases.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140075828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. A. Chelombitko, G. V. Morgunova, N. Yu. Strochkova, K. G. Lyamzaev
{"title":"Geroprotective Effect of the Mitochondrial-Targeted Antioxidant SkQBerb in a Model of the Chronological Aging of MB135 Human Myoblasts","authors":"M. A. Chelombitko, G. V. Morgunova, N. Yu. Strochkova, K. G. Lyamzaev","doi":"10.1134/S2079057024600149","DOIUrl":"10.1134/S2079057024600149","url":null,"abstract":"<p>Background: The field of gerontology is actively seeking senolytics and senomorphs that can influence the quantity and activity of senescent cells in the body. Previous studies have demonstrated the geroprotective properties of mitochondrial-directed compounds based on plastoquinone and berberine in various in vitro and in vivo models. Thus, it is plausible that SkQBerb, a mitochondrial-targeted compound combining berberine and plastoquinone, may exhibit higher geroprotective potential compared to previously studied compounds. Aim: The aim of this study is to investigate the geroprotective activity of SkQBerb in a chronological aging model using MB135 myoblasts. Experimental: The effect of SkQBerb on various aging characteristics of human MB135 myoblasts is assessed. Histochemical staining for β-galactosidase is performed using a commercially available kit. The levels of proinflammatory cytokines IL-6 and IL-8 are determined using pre-made immunoassay kits. Additionally, Western blotting was employed to evaluate the levels of p21, pRb (Ser807/811), and LC3B proteins. Results: Analysis of the results reveals that SkQBerb, at concentrations ranging from 20–100 nM, effectively suppresses the accumulation of senescent cells in MB135 cells subjected to chronological aging. Furthermore, it significantly reduces the levels of IL-6 and IL-8, which are key factors associated with the secretory phenotype. Conclusion: The findings of this study suggest the potential geroprotective and senomorphic effect of SkQBerb. These results open up possibilities for utilizing this mitochondrial-targeted compound as a geroprotector in future applications.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140075471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of the Serotonin Pathway of Tryptophan Metabolism in the Development of Neuroinflammation in Alzheimer’s Disease","authors":"A. S. Fomin, S. P. Sergeeva","doi":"10.1134/S207905702460023X","DOIUrl":"10.1134/S207905702460023X","url":null,"abstract":"<p>Despite the fact that more than 90% of tryptophan is metabolized via the kynurenine pathway, the serotonin pathway is of great importance for the functioning of the central nervous system. The main products of this pathway are serotonin and melatonin. They provide maintenance of the sleep–wake mode, modulation of oxidative stress activity, apoptosis of neurons and glial elements, regeneration and neuroinflammation. In the pathogenesis of Alzheimer’s disease, neuroinflammation plays one of the main roles. Melatonin and serotonin, being modulators of its intensity, as well as an important component of neurochemical interactions that provide cognitive functions, can be considered as targets for preventive and therapeutic effects.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140075508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. A. Akopyan, I. D. Strazhesko, A. A. Moskalev, I. A. Orlova
{"title":"The Rate of Aging and Its Association with Risk Factors of Cardiovascular Diseases","authors":"A. A. Akopyan, I. D. Strazhesko, A. A. Moskalev, I. A. Orlova","doi":"10.1134/S2079057024600228","DOIUrl":"10.1134/S2079057024600228","url":null,"abstract":"<p>Background: Biological age is a better predictor of morbidity and mortality associated with chronic age-related diseases than chronological age. The estimated difference between biological and chronological age can reveal an individual’s rate of aging. Aim: The aim of this study was to assess the association of cardiovascular risk factors with the rate of aging in people without cardiovascular diseases. Materials and methods: We calculated biological artery age and found associations of “old” arteries and rate of aging with risk factors of cardiovascular diseases in 143 adults without cardiovascular diseases. The data were analyzed by their categorization into 3 tertiles using regression methods. Results: The increased biological age of the arteries compared to the chronological age was associated with the chronological age (<i>p</i> < 0.001; ОR = 0.55; 95% CI: 0.43–0.71) and hypertension (<i>p</i> = 0.002; ОR = 6.04; 95% CI: 1.98–18.42) in general group, age (<i>p</i> < 0.001; ОR = 0.45; 95% CI: 0.30–0.68), hypertension (<i>p</i> = 0.004; ОR = 12.79; 95% CI: 2.25–72.55) and family history of oncology (<i>p</i> = 0.036; ОR = 0.14; 95% CI: 0.02–0.88) in women subgroup and age (<i>p</i> = 0.001; ОR = 0.45; 95% CI: 0.28–0.76) and 3rd tertile of glycated hemoglobin (<i>p</i> = 0.041; ОR = 65.05; 95% CI: 1.19–3548.29) in men subgroup. Difference between biological and chronological age in a group of “old” arteries was associated with chronological age (<i>p</i> = 0.001; β = –1.24; 95% CI: –1.95…–0.53) and with chronological age (<i>p</i> < 0.001; β = 1.71; 95% CI: 1.06–2.36) and 3rd tertile of glycated hemoglobin (<i>p</i> = 0.009; β = –4.78; 95% CI: –8.32…–1.24) in group of “young” arteries. Conclusion: This study demonstrates that accelerated arterial aging is associated with hypertension and high levels of glycated hemoglobin.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140075519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. A. Eruslanova, S. O. Zhikrivetskaya, Yu. V. Kotovskaya, O. N. Tkacheva
{"title":"Association between Telomere Length and Geriatric Status in Centenarians","authors":"K. A. Eruslanova, S. O. Zhikrivetskaya, Yu. V. Kotovskaya, O. N. Tkacheva","doi":"10.1134/S2079057024600253","DOIUrl":"10.1134/S2079057024600253","url":null,"abstract":"<p>Aim: To evaluate the association between telomere length and frailty and individual geriatric syndromes in older adults. Materials and methods: The database of a hundred-year-old citizen of the city of Moscow was analyzed. The analysis was carried out using the data driven from the Comprehensive Geriatric Assessment (CGA), in particular, Age is not a Hindrance Scale, the Barthel index, Instrumental Activities of Daily Living (IADL), Mini Nutritional Assessment (MNA), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS-15). DNA was isolated from frozen blood and a study of telomere length was performed. The comparison of telomere length in groups of patients with frailty and individual geriatric syndromes was carried out. Results: The study involved 60 people (98 ± 1.8 years old, 86.7% women). The analysis found no differences in telomere length in research participants with and without frailty, as well as in the analysis of individual geriatric syndromes. No correlation was found between telomere length and the results of comprehensive geriatric assessment scales. There was no difference in telomere length in patients who died within 3 years of follow-up and those who did not. Conclusion: No relationship was found between telomere length and frailty. Thus, telomere length cannot be considered as a reliable biomarker of functional aging.</p>","PeriodicalId":44756,"journal":{"name":"Advances in Gerontology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140076266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}