Advances in Gerontology最新文献

The study is aimed at determining age-related changes in ocular tissues of crab-eating macaque (Macaca fascicularis). To this end, we measured the concentrations of a total of 71 major metabolites in aqueous humor, vitreous humor, and lens of two groups of animals, young (4-year-old, n = 6) and aged (21-year-old and 27-year-old, n = 2) macaques. Significant age-related changes were revealed for all three tissues. In the lens, the most significant changes were found for cytoprotective compounds – antioxidants, osmolytes, and molecular ultraviolet (UV) filters: the concentrations of these metabolites in the lenses of aged animals are much lower. The observed changes contribute to increased oxidative stress and predispose the lens to the development of cataracts. The majority of cytoprotective metabolites are synthetized in the lens epithelium. Findings of this work indicate that the observed age-related changes may be caused by the impairment of the lens epithelial cells leading to the increase of oxidative stress in the lens nucleus and developing of age-related cataracts.

Genotoxic and cytotoxic drugs, widely used in anticancer therapy, target proliferating cells and induce cell death through a variety of cell cycle-dependent mechanisms. The mechanisms of the delayed toxicity induced by chemotherapy are not fully understood. The accumulation of senescent cells may underlie some of the mechanisms for the development of late adverse effects of chemotherapy on muscle tissue. Cellular models are necessary for the development of therapeutic approaches to these side effects. In our study we used human immortalized myoblast MB135 to optimize the protocol for obtaining the senescent phenotype of muscle cells under the influence of chemotherapeutic drugs such as doxorubicin, cisplatin and arsenic trioxide (As₂O₃). We evaluated the dynamics of changes in senescence proteins pRb, p21 and p53 and SASP-associated proteins such as TNF, IL-1b, IL-6, IL-8, CXCL2, GDF15 using Western blot, RT-PCR and ELISA. Cell senescence was confirmed by the measurement of cell senescence index by flow cytometry after 7 days of exposure to chemotherapeutic agents. The obtained results indicate that all three investigated chemotherapeutic compounds induce the appearance of senescence markers, but the dynamics of these changes are somewhat different for them, which may reflect differences in the mechanisms of senescence phenotype induction.

The research of aging, rejuvenation and life extension has been notoriously characterized by a multitude of often contradictory approaches, both in terms of theoretical concepts as well as possible practical interventions. This work will explore a general taxonomy of these approaches that seems to be ubiquitous in the history of aging and longevity research. The taxonomy will juxtapose between reductionist/therapeutic and holistic/hygienic approaches to potential rejuvenating and life-extending interventions. Both approaches sought to achieve biological equilibrium and constancy of internal environment, yet emphasized diverging means and diverging perceptions of what constitutes equilibrium and constancy. The reductionist approach saw the human body as a machine in need of repair and internal adjustment and equilibration, seeking to achieve material homeostasis by eliminating damaging agents and introducing biological replacements, in other words, working by subtraction and addition toward balance. The holistic approach, in contrast, focused on the equilibration of the organism as a unit within the environment, strongly emphasizing the direct sustaining and revitalizing power of the mind and hygienic regulation of behavior. In the holistic approach, internal equilibrium was sought not so much through calibrating intrusions, but through resistance to intrusions. The apparent relative weight of each approach in academic and public discourse will be shown to change with time, in several western countries, with a special focus on France, Austria and Germany, in the first half of the 20th century. This work (the first part in a sequence of two) will demonstrate the initial fascination with reductionist rejuvenation and life extension attempts, in this time and area, that were encouraging, yet eventually came short of the original promise.

The relationships between blood biomarkers, frailty, and the risk of death of people diagnosed with COVID-19 is unclear. In the current investigation we decided to analyze the collective effect of multiple biomarkers (laboratory markers of inflammation, blood biochemistry deviations, comorbidity, demographics) on mortality in people diagnosed with COVID-19. We analyzed baseline data of one hundred fifty-five patients (age range from twenty-six to ninety-four) diagnosed with COVID-19. Thirty-seven parameters (including major morbidities) were used to derive the frailty index (FI) and calculate the risk of death as a function of FI and individual biomarkers. Discriminative ability was assessed by the area under the receiver-operating characteristic (ROC curves). The mean frailty index was 0.17 (SD = 0.10), FI of those who survived was 0.11 (SD = 0.078) and those who died was 0.22 (SD = 0.093). In a sex-adjusted model, the FI was a more powerful predictor for mortality than age. The ROC analysis showed that models involving FI as a feature have good discriminative ability for predicting COVID-19 mortality: AUC for age was 0.77, for the FI it was 0.82, and for the fully adjusted model (age + FI) it was 0.84. Thus, the systemic effect of multiple biological processes comprising aging are elucidated using the Frailty Index approach. Assessment of the frailty index at the time of admission of a patient with COVID-19 to the clinic can help to predict the high risks of severe disease and mortality.

In spite of numerous studies, pathogenesis of the sporadic (not inherited) form of Alzheimer’s disease (AD) still remains largely unclear; nevertheless, there is general consensus as regards the complex involvement of neurotrophic factors and neurotransmitters in the mechanisms of this disease. In light of recent data on the physical interaction between serotonin (5-HT) receptors and receptors of the brain-derived neurotrophic factor (BDNF), the reciprocal modulation between 5-HT and BDNF systems is of particular interest, inter alia, in the context of AD development. The OXYS lineage of prematurely aging rats is a unique model of sporadic AD. Previously, it has been reported on the changed neurotrophin balance in the brain of these animals; however, the changes in the expression of BDNF and its receptors in the dynamics of development of AD symptoms has been studied insufficiently. Even less is known about the patterns of expression of 5-HT receptors in OXYS rat brain. In the present work, we have compared the expression of BDNF and its receptors, TrkB and p75^NTR, as well as serotonin 5-НТ_1А, 5-НТ_2А, 5-НТ₄ and 5-НТ₇ receptors in the brain of OXYS and Wistar rats aged 20 days, 3.5 and 18 months. The frontal cortex of 20-day-old OXYS rats demonstrated a significant increase in the mRNA level of the Bdnf, Htr2a and Htr7 genes and, at the same time, a decrease in the ratio of phosphorylated and nonphosphorylated forms of the TrkB receptor. In the hippocampus of 20-day-old OXYS rats, the mRNA levels of the Bdnf, Htr1a, Htr2a and Htr4 genes are also elevated. A substantially higher mRNA level of the above genes for 5-HT receptors was observed in the hippocampus of OXYS rats also at the age of 3.5 months, in the period of manifestation of the first AD symptoms. The nature of change in gene expression patterns indicates the potential involvement of 5-HT receptors in suppression of the TrkB receptor function in the early period of postnatal development of OXYS rats, which may be one of the mechanisms, through which 5-HT receptors are involved in the development of pathological process in the period of manifestation of AD symptoms in OXYS rats.

Circadian rhythms ensure the synchronization of the physiology of cells and tissues in accordance with daily changes in the environment. These rhythms are maintained by transcriptional oscillators located in various organism cells. One of the rhythm sensors for the circadian clock is the intake of nutrients, this synchronizer is especially important in peripheral tissues. With age, the work of both the central and peripheral clock is disturbed. In old age, the amplitude of rhythms decreases and the peaks of expression of clock genes shift. Such changes affect not only the circadian, but also other rhythms. Promising ways to maintain circadian rhythms are a variety of dietary patterns, including both calorie restriction, well known for its ability to prolong the lifespan of laboratory animals, and time-restricted feeding. It is now known that intracellular metabolic sensors are also involved in regulation of the circadian clock. Among these sensors, it should be especially noted AMPK, which coordinates many catabolic and anabolic processes and participates in the implementation of the effect of calorie restriction. It is assumed that non-drug modulation of AMPK activity will not only help fight metabolic disorders, but also maintain circadian rhythms. The review considers the role of AMPK and some other metabolic sensors in the regulation of the circadian clock.

The opposition between reductionism and holism can be seen as an overarching theme in the history of aging, longevity and rejuvenation research. As a rule, the initial fascination with reductionist rejuvenation and life extension attempts, striving to tweak and rearrange parts of the human “machine,” in time, is superseded with more holistic perceptions of health maintenance in old age, emphasizing hygienic regulation of behavior and the revitalizing power of the mind. The initial high hopes for dramatic reductionist rejuvenation are often succeeded by more skeptical and cautious visions, yet the optimism may return later on. The cycle of hopefulness will be exemplified by the works of some of the prominent French and German-speaking researchers of aging, in the first half of the 20th century. The present work (the second part in a sequence of two) will focus on the recoil process from reductionist toward holistic conceptual preferences, in this time and area. Several open philosophical and practical questions will be posed with reference to the opposition between reductionism and holism in the history of aging research and anti-aging practice.

The study investigated the effect of refraining from going out during the coronavirus disease 2019 pandemic on physical function in community-dwelling older adults. The study included 49 patients who underwent home-visit rehabilitation. Four parameters of physical function—grip strength, five-times sit-to-stand test, single-leg stance test, and standing test for imbalance and disequilibrium (SIDE)—were assessed. They were evaluated before (March 2020) and after (May 2020) the state emergency was imposed, and the results were compared. The grip strength decreased significantly. A significant difference was also observed in the proportion of different SIDE levels in the study group before and after the implementation of the state emergency. The number of SIDE 2a or lower patients increased during the state emergency (p < 0.001). Comprehensive community support and rehabilitation are necessary to maintain physical function in older individuals. In particular, we believe that there is a need to utilize remote rehabilitation using digital devices (such as internet-based guidance) so that older adults can continue to exercise at home.

As organs age morpho-functional changes of organs and tissues become pathological disrupting the quality of life and providing an aggravating effect on the course of underlying disease which requires a special treatment approach. The research purpose is the study of particular features of the clinical, immunological and morphological manifestations of the venous trophic ulcers in the elderly and senile aged patients. All 375 patients are suffering from venous trophic ulcers have been examined. All the patients are divided into three age groups according to the WHO classification: 1st group (middle-aged)—94 patients; 2nd group (elderly)—146 patients; 3rd group (seniors)—135 persons. Levels of IgA, IgG, IgM, IL-1β, TNF-α were measured in wound exudate. The content of vascular endothelial growth factor in wound exudate samples had been studied as well. The morphological examination of the bottom and edge parts of trophic ulcers has been carried out. It has been revealed that elderly and senile aged patients with involutional changes and long-term chronic inflammation in the zone of trophic ulcers had more prominent morphological changes and disruption synthesis of non-specific immunity proteins that slow down processes of recovery.