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The role of mitochondrial energy metabolism in cell senescence
Zima, Michal ; Trnka, Jan (advisor) ; Pecinová, Alena (referee)
Cellular senescence represents status, when the cells cease to divide and remain in permanent cell cycle arrest. Senescence is considered to be an active response of the cell to various extrinsic and intrinsic types of stress such as certain oncogene activation, exposing to several cytokines or drugs and damaged and/or uncapped telomeres. Senescent cells are characterised by extensive modification of gene expression, flattened and enlargement of cellular body. Hypothetically, altered gene expression may lead also to increase of certain surface proteins expression. Such protein can be L1 cell adhesive molecule (L1CAM), which is expressed heterogeneously within the population. This Thesis describes current knowledge of cellular senescence, the mechanism, which may result in establishment of senescence phenotype, and also the characteristic markers of senescence. Thesis also puts together the heterogeneity of L1CAM expression in A375 senescent cells with oxygen consumption rate and extracellular acidification rate performed by Seahorse XFe24 metabolic analyser. Therefore, ells were sorted according to their levels of expressing L1CAM onto low and high L1CAM expressing subpopulations. Obtained data show potential correlation between the rate of L1CAM expression in A375 cells and the metabolic rate. Key...
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Inclusion of people over 50 in the Czech Republic
Vorel, Tomáš ; Ondrušová, Jiřina (advisor) ; Nová, Monika (referee)
World population is ageing and in Europe the situation is especially alarming. In the next two decades the ratio of people over 65 years of age is expected to double. This threatens long-term sustainability of welfare systems. The debate about future developments has been going on since the turn of the century. Based on this debate the European Union defined improving the inclusion of people over 50 as the main solution to this problem. The means to achieving this goal have been identified at the level of the labour market, disease prevention and lifelong learning. The specific instruments are: 1) increasing the participation of older workers in the labour market by increasing retirement age, introducing penalties for early retirement, promoting retraining of older and increasing retraining efficiency, 2) restructuring of pension systems and provision of social services and 3) strengthening participation of older people in society, applying the principles of active aging at all levels of social life and increasing the quality and variety of lifelong learning opportunities. This paper analyses the situation of persons over 50 years of age in the Czech Republic in terms of their position in the labour market, participation in social life and quality of life in the context of the strategic concept of...
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Vliv chemoterapie a genotoxického stresu na imunologické vlastnosti nádorových buněk.
Horňáková, Michaela ; Reiniš, Milan (advisor) ; Drbal, Karel (referee)
Cancer treatment includes the use of chemotherapeutic agents, which have various effects on tumour cells, such as direct toxicity to cancer cells, immunogenic cell death induction and changes in cancer cells phenotype. Throughout the last decade many researchers have been focusing on the induction of genotoxic stress and cellular senescence, which chemotherapy can trigger. Even though induction of senescence in cancer cells represents an important mechanism for tumour suppression, there has been increasing evidence that shifting cancer cells into a senescent state by chemotherapy is not always beneficial. Senescent cells are associated with a specific secretory phenotype, which allows such cells to alter their microenvironment, modulate anti-tumour immunity, induce tumour suppression and even promote cancer development. Therefore, senescent cells elimination by innate or specific immunity, which can be boosted by immunotherapy, can be an important barrier preventing tumour growth. Powered by TCPDF (www.tcpdf.org)
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A potential role of DAXX in cell cycle arrest and cellular senescence
Valášek, Ján ; Hanzlíková, Hana (advisor) ; Vopálenský, Václav (referee)
Death domain-associated protein 6 (DAXX) is a multifunctional protein involved in diverse cellular processes. It acts as a histone chaperone or regulator of transcription and apoptosis, in which is its role quite controversial. DAXX also participates in regulation of cell DNA damage response (DDR). DAXX co-creates and stabilizes complex with Mdm2, which negatively regulates the stability of p53, an important tumor suppressor, which is a part of signalling node in the DDR. If DNA damage is not lethal for the cell and unables it to proliferate, the irreversible state of cell cycle called cellular senescence takes place. Under physiological conditions, induction of senescence can prevent the development of tumorigenesis. Therefore, the description of mechanisms involved in the induction of senescence has potential clinical significance. In my thesis, I aimed to determine changes in the level of DAXX protein in senescent cells and to characterize the manner of its regulation. In tumor cells MCF-7 and primary BJ fibroblasts, I observed decrease in DAXX protein level and its regulation. I tested the hypothesis according to which an increase in DAXX level before DNA damage canprevent induction of cellular senescence, or increase in its expression during senescence can cause recovery of cell proliferation....
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Charakterizace vlivu senescence na indukci a regulaci smrti nádorových buněk
Nováková, Gita ; Anděra, Ladislav (advisor) ; Truksa, Jaroslav (referee)
4 Abstract Senescence is a specific cell state distinquished by cessation of cell division and proliferation and changes in gene expression. Normal cells enter senescence after distinct number of cell divisions or in case of an unrepairable damage. Senescence in cancer cells can be induced by subliminal stress as sublethal treatment with certain drugs. Senescent cancer cells persist in the tissue and may secrete a number of factors and nutrients affecting surrounding cells. Senescence can thus change the response of cancer cells to various apoptogens during cancer therapy. In this study, we focused on the elucidation of presumed differences between normal proliferating and senescent cancer cells in their response to selected apoptogens. Implementing bromodeoxyuridine (BrdU)-mediated replication stress in cancer cells derived from pancreatic (PANC-1) or mesothelioma (H28) tumors, we efficiently forced these cells to acquire senescent phenotype. We document that these senescent cells gain higher resistance to combined TRAIL and homoharringtonine (HHT) treatment and enhance sensitivity to other apoptogens such as FasL, camptothecin and mVES. These cells also showed increased expression of anti-apoptotic protein c-FLIP in senescent cells and changes in the expression of some Bcl-2 family proteins....
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Role of DNA damage response signalling in induction and maintenance of cellular senescence
Pešina, František ; Hodný, Zdeněk (advisor) ; Janoštiak, Radoslav (referee)
Cellular senescence is a state of permanent growth arrest. It is induced by many stimuli, including telomere shortening, DNA damage, oncogene hyperstimulation, chromatin perturbation and various stresses by which are cells affected. Researches showed central role of two pathways in induction and maintenance of this state. These are the p53/21 and p16/RB. The extent and dynamics of their activation by various stimuli is different. Slightly different is also their function in induction and maintenance of senescence. These differences are depicted and compared in this work.
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Cytokinins and plant senescence
Pokorná, Monika ; Lipavská, Helena (advisor) ; Kutík, Jaromír (referee)
Senescence is a natural process, which is a part of plant developmental programme. However, the onset of senescence can be greatly influenced by external conditions. An important part of plant senescence is a senescence of leaves manifested by chloroplasts breakdown. That is connected to mobilization of nitrogen contained in proteins, which provide their function. However, the correct timing of natural senescence is substantive for the plant. The initiation as well as the process of natural senescence is influenced by several factors. Senescence is in varying degrees controlled by phytohormones, regulation factors and it is also driven by epigeneticall processes. Leaf senescence can be caused by several exogenous (light conditions, temperature, water and mineral availability, pathogen attack) and internal (carbohydrate levels, hormones, age, developmental stage) conditions. As well as many other developmental stages, senescence is greatly regulated by phytohormones. Ethylene, abscisic acid, salicyl acid and methyljasmonate support leaf aging, on contrary cytokinins delay senescence associated processes. Studying of cytokinin with chlorophyll analysis is an important part of every study of senescence. This work summarizes literature information of regulation of senescence with an accent on the role...
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Physiological mechanisms of aging in maless of model insect species
PROVAZNÍK, Jan
Trade-off between reproduction and longevity is a widely accepted fact, yet proximate mechanisms are scarcely understood. In this work I tested differences in lifespan between diapause and non-diapause males of a model insect, the linden bug Pyrrhocoris apterus. Also the role of juvenile hormone in regulation of longevity and immunity (measured by relative phenoloxidase activity) was assessed. In addition to that, I examined if juvenile hormone is the mediator of reduction in longevity induced by mating.
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Expectations of senior citizens prior to and after the moving in the seniors houses
DVOŘÁKOVÁ, Martina
In today´s society, there are an increasing number of seniors who are not conforming to changes, which come with ageing. They seek a help of social services either due to health problems, the loss of self-sufficiency, the incapability of taking self-care of themselves, or due to any difficulties of social status. Major changes of social services were initiated by the Act No. 108/2006 as amended and the consequent regulation No. 505/2006, which came into effect on January 1, 2007. The changes are based on new approach to social services, their forms, categories and given conditions. The Act has also introduced a new welfare, which is intended to support additional care either at home, or in convalescent homes. According to the abovementioned act, the retirement homes provide accommodation to seniors with reduced self-sufficiency caused by age that need regular assistance of another person. Basic services provided in the retirement persons homes are: accommodation, meals, gathering, help with daily self-care and personal hygiene, socializing, social-therapeutic activities and legal aid with individual rights, lawful requirements and arrangement of personal matters. The objective of this thesis is to define the problem of old age and senescence, psychical and social alterations of seniors, their needs and changes in communication. The thesis also deals with the adaptation to aging and stress caused by entering a retirement home. The survey for this study was carried out in the retirement home at Horní Planá (Czech Republic). A half of its occupants were interviewed to learn how they made their decision to stay there, the way of adaptation and general satisfaction with services. The conclusions of this study are to be aimed particularly to needs of the retirement home at Horní Planá as to improve the quality of provided services.
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