Advances in Gerontology最新文献

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.

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.

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.

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 (p < 0.001; ОR = 0.55; 95% CI: 0.43–0.71) and hypertension (p = 0.002; ОR = 6.04; 95% CI: 1.98–18.42) in general group, age (p < 0.001; ОR = 0.45; 95% CI: 0.30–0.68), hypertension (p = 0.004; ОR = 12.79; 95% CI: 2.25–72.55) and family history of oncology (p = 0.036; ОR = 0.14; 95% CI: 0.02–0.88) in women subgroup and age (p = 0.001; ОR = 0.45; 95% CI: 0.28–0.76) and 3rd tertile of glycated hemoglobin (p = 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 (p = 0.001; β = –1.24; 95% CI: –1.95…–0.53) and with chronological age (p < 0.001; β = 1.71; 95% CI: 1.06–2.36) and 3rd tertile of glycated hemoglobin (p = 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.

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.

Human aging is associated with an increased risk of various geriatric syndromes, cognitive impairment being among the most frequent. The most prominent form of the cognitive impairment—dementia—has become one of the major course of dependency in older and oldest old patients. Nevertheless, it has been shown that despite the fact that various parts of the brain change structurally over time due to natural aging or diseases, it does not necessarily manifest into clinical symptoms for some older people. Therefore, there is a dissociation of the severity of morphological and functional brain changes. The review presents current data on adaptive mechanisms that ensure the preservation of neurocognitive activity during aging process. In addition to the concept of brain and cognitive reserves, it discusses different mechanisms of neurocognitive maintenance and compensation both in the norm and in the development of Alzheimer’s disease. The possibility of their clinical and instrumental assessment and practical significance are discussed.

The process of aging is a complex biological phenomenon that is influenced by multiple factors, including genetics, environment, and lifestyle. Recent studies have shown that epigenetic modifications play an important role in the aging process, as they regulate gene expression and ultimately affect cellular function. Epigenetic modifications include DNA methylation, histone modification, and non-coding RNA expression, among others. The authors of the review discuss the role of DNA methylation in regulating gene expression and its relationship to age-related diseases such as cancer and neurodegeneration. Also, the role of histone modification and its impact on chromatin structure and gene expression is reviewed in the article. Additionally, review provides information on the involvement of molecular hallmarks of aging in age-related diseases. Understanding the role of epigenetic mechanisms in aging is crucial for developing new interventions that could potentially slow down or even reverse the aging process.

Brain aging is part of the aging of the whole body, largely determining the success of general aging and the quality of life of an older person. Brain aging is a complex multifactorial process that occurs throughout a human’s life, which includes changes at subcellular, tissue, and organ levels as well as at physiological level, mediating changes in neurophysiological (cognitive) functions. The review provides up-to-date data on morphological and physiological changes observed during natural aging; it discusses various phenotypes of brain aging, including both pathologically accelerated and “supernormal” aging; questions of the division between the norm and pathology are raised in the context of changes observed during brain aging; the factors both accelerating and decelerating the aging processes of the brain are considered along with linkage of natural aging with neurodegenerative and cerebrovascular diseases.

Studying the mechanisms of aging is one of the most important goals of modern science. A significant amount of data on the processes associated with a decrease in the functional ability to regenerate, cell proliferation and resistance to adverse factors with age has been accumulated due to fundamental research. The aim of the review was to study the mechanism of drugs with the senolytic activity, to determine the main targets of their effect at the cellular level, and also to evaluate the prospects for their clinical use. The relevance of this topic is confirmed by the increasing number of clinical trials of senolytics, many of which have ambiguous results and require further analysis and elimination of revealed difficulties and shortcomings. We reviewed the literature on Pubmed and Scopus platforms over the past 10 years in order to find information about the mechanisms of senotherapy and the possibility of using senolytics in clinical medicine. The focus was on those senolytic drugs that were used in clinical studies.

Numerous studies have shown that mitochondria-targeted antioxidant SkQ1 can increase the lifespan of many species and suppress the development of various age-related diseases. Previously we demonstrated that SkQ1 suppresses all manifestations of accelerated senescence in OXYS rats, including the development of the main signs of Alzheimer’s disease (AD). GABA and glutamate are two of the most abundant neurotransmitters in the central nervous system, and it was showed that changes in their signaling accompany aging and the development of AD. Previously, we showed delicate age-related changes of the components of glutamate/GABA system in Wistar and OXYS rats, a unique model of AD. Here we investigated the influence of the treatment with SkQ1 from 12 through 18 months of age (that is, during the active progression of AD-like pathology) on glutamate/GABA system in the rat hippocampus. Our data demonstrated that the neuroprotective effects of long-term administration of SkQ1 are mediated by its effect on the GABAergic but not the glutamatergic system in the hippocampus of Wistar and OXYS rats. Western blotting revealed an increase in the level of glutamate decarboxylase GAD67 in rats of both strains, a decrease in the GABA transporter GAT1 in Wistar rats, and a tendency towards abrogation of the increased level of GABA receptor subunits GABAAr1 in OXYS rats. Thus, we showed that the neuroprotective effects of long-term treatment with SkQ1 are mediated by its effect on the GABAergic but not the glutamatergic system in the hippocampus of Wistar and OXYS rats.