Huntington disease (HD) is a fatal neurodegenerative disease caused by CAG tract expansion in the huntingtin (HTT) gene, which results in production of mutant huntingtin (mtHTT) protein. Although mtHTT is expressed throughout life, onset of HD symptoms typically begins in mid-life, around 35 to 50 years of age. Characteristic HD symptoms include motor, cognitive, and psychiatric abnormalities. The emergence of symptoms in adulthood suggests that aging may play a role in HD pathogenesis. Furthermore, markers of accelerated aging can be observed in HD patients, including telomere attrition, epigenetic alterations, and mitochondrial dysfunction. Our lab has previously observed that induction of age-like changes by treatment with progerin, the mutant protein that causes Hutchinson-Gilford Progeria Syndrome, enhances HD phenotypes and contributes to pathogenesis in HD neurons. Taken together, these findings suggest a link between aging and HD, with implications for potential therapeutic benefits from anti-aging treatment. Our lab has conducted a young blood anti-aging trial in which aged HD and wild-type (WT) mice were injected with plasma from young WT or HD mice. Previous work in our lab confirmed that cortical aging markers decline with age at the protein level and are differentially affected by young blood treatment. In this study, we observed a significant effect of age on striatal expression of aging markers, Grin1 and Lmnb1. Varying effects of young blood anti-aging treatment were observed on the genes of interest.

The present diploma thesis is focused on the selected anti-aging substances in cosmetic products. The literature research provided us with the knowledge of essential skin characteristics and factors influencing the aging process. Furthermore, the thesis describes the basic physical forms of cosmetic products, the basic cosmetic materials and the current trends in the usage of anti-aging substances. The experimental part subsumes altogether four physical forms of cosmetic products – tonics, serums, masks and creams. In this work was testid a new anti-aging compound, developer by French company SOLABIA, which provided the company Miša a Harašta s.r.o. (M+H). It has tested four components: Fucogel, Camaderm Gly, Viniderm and Omega Ceramid. These anti-aging substances were addend to the four technology cosmetic form, which were prepared in our laboratory. Subsequently, the pH stability of the products was measured together with the rheological measuring and skin hydration measuring. All of the samples proved to be pH stable. The highest stability of viscosity and consistence was identified for masks and creams. It was found out that the added anti-aging substances have no impact on the stability of pH, viscosity and consistency. The skin hydration measuring proved that the anti-aging substances Vinidem and Camadem Gly have the greatest moisturising qualities.

The adhesive and frictional response of an AFM tip connected to a substrate through supramolecular host–guest complexes is investigated by dynamic Monte Carlo simulations. Here, the variation of the pull-off force with the unloading rate recently observed in experiments is unraveled by evidencing simultaneous (progressive) breaking of the bonds at fast (slow) rates. The model reveals the origin of the observed plateaus in the retraction force as a function of the tip-surface distance, showing that they result from the tip geometrical features. In lateral sliding, the model exhibits a wide range of dynamic behaviors ranging from smooth sliding to stick-slip at different velocities, with the average friction force determined by the characteristic formation/rupture rates of the complexes. In particular, it is shown that for some molecular complexes friction can become almost constant over a wide range of velocities. Also, we show the possibility of exploiting the ageing effect through slide-hold-slide experiments, in order to infer the characteristic formation rate. Finally, our model predicts a novel ‘‘antiageing’’ effect which is characterized by a decrease of the static friction force with the hold time. Such an effect is explained in terms of enhancement of adhesion during sliding, especially observed at high driving velocities.

Made available in DSpace on 2016-06-23T12:15:52Z (GMT). No. of bitstreams: 2 11.pdf: 1171017 bytes, checksum: fd87d6f92747562e0cca8362bb88c606 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2013 / Made available in DSpace on 2016-07-05T22:38:00Z (GMT). No. of bitstreams: 3 11.pdf.txt: 125000 bytes, checksum: 5a305744c1238f1b48f95a04d4ce0cd8 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 11.pdf: 1171017 bytes, checksum: fd87d6f92747562e0cca8362bb88c606 (MD5) Previous issue date: 2013 / Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos/Farmanguinhos. Rio de Janeiro, RJ, Brasil. / Atualmente um ser humano vive mais tempo do que há 100 anos, porém sob forte estresse e em um meio ambiente altamente poluído. Essa nova realidade fez aumentar a incidência de doenças como câncer e doenças crônico-degenerativas. Em contrapartida as indústrias farmacêuticas e cosméticas buscaram alternativas para o tratamento dessas novas doenças e para melhora do bem-estar e aparência da população, respectivamente. No entanto, especialistas da área dermatológica chamam a atenção para o uso indiscriminado dos produtos cosméticos, principalmente devido ao marketing exagerado visando à venda destes produtos. Sendo assim, é importante que tanto a eficácia, assim como a segurança desses produtos seja avaliada. Devido a razões científicas e éticas, determinar esses testes in vitro se tornou um objetivo essencial e fundamental em todo o mundo. O presente trabalho tem como objetivo avaliar os métodos descritos na literatura para descoberta de princípios ativos com atividade antienvelhecimento visando o desenvolvimento de cosmecêuticos, levando-se em consideração a avaliação de segurança e eficácia das substâncias testadas. Métodos in vitro foram selecionados em revistas indexadas, patentes e legislação nacional vigente. Por ser uma classe recente, a legislação que regulamenta o registro de cosmecêuticos com atividade antienvelhecimento não existe. Observamos ainda, uma grande quantidade de métodos onde é possível avaliar a eficácia de substâncias quanto sua atividade hidratante, antirrugas, despigmentante, fotoprotetora, anti-inflamatória e antiflacidez. Com isso, podemos concluir que mesmo com a escassez de legislação para regulamentar cosmecêuticos, existem técnicas descritas na literatura, validadas ou não, que estão de acordo com os princípios dos três Rs de Russel e Burch, e são úteis para avaliar a atividade antienvelhecimento de princípios ativos. / Nowadays the humans live longer than 100 years ago, but under severe stress and in a highly polluted environment. This new reality has increased the incidence of diseases such as cancer and chronic degenerative diseases. In contrast to pharmaceutical and cosmetic industries sought alternatives to treat these new diseases and improved well-being and appearance of the population, respectively. However, specialists in dermatology draw attention to the widespread use of cosmetic products, mainly due to marketing hype aimed at selling these products. Therefore, it is important that both the effectiveness and safety of these products are evaluated. Due to scientific and ethical reasons, these tests determine in vitro has become an essential objective and fundamental worldwide. This study aims to evaluate the methods described in the literature for discovery of active ingredients with anti-aging activity aimed at developing cosmeceuticals, taking into account the evaluation of safety and efficacy of the tested substances. In vitro methods were selected in refereed journals, patents and current national legislation. Because it is a recent class, the legislation governing the registration of cosmeceuticals in antiaging activity does not exist. We also observed a large quantity of methods in which you can evaluate the effectiveness of substances as their activity moisturizer, wrinkle, depigmentation, sunscreen, anti-inflammatory and anti-sagging. With this, we can conclude that even with the lack of legislation to regulate cosmeceuticals, are described in the literature, validated or not, that is in accordance with the principles of the “three Rs” of Russell and Burch, and is useful to evaluate the activity anti-aging active ingredients.

The main objective of this thesis is to develop a critical approach to the recent anti-aging discourse which has become popular after the 1990&rsquo / s. Anti-aging movement is concerned with certain implementations which aspire to make individuals live longer and healthier by controlling and disciplining their bodily conditions and lifestyle choices. This study attempts to examine certain perceptions and assumptions of anti-aging discourse about body, living and keeping alive peculiar to late modern times by taking into consideration three popular emblematic anti-aging books. For this aim, the techniques, recommendations, suggestions and basic premises of popular anti-aging books are examined in terms of the question whether anti-aging discourse presents a new project concerning body and lifestyle, or not. In order to answer this question, Foucauldian theory on &ldquo / the power over life&rdquo / and Sontag&rsquo / s approach to &ldquo / the metaphorical representation of illness in late modern times&rdquo / are employed for constructing the theoretical basis of this thesis. The examination of anti-aging discourse reveals that, this discourse redefines the meaning of age and reinterprets human temporality by narrating aging process with certain metaphors. Moreover, it is seen that anti-aging discourse transforms the aging process into a performative sphere by representing the aging as a merely biological and controllable situation.

A esperança é uma emoção importante no dia-a-dia das pessoas, mas que ainda não foi devidamente compreendida pelos estudos do comportamento humano. Utilizada como argumento de vendas de produtos que prometem mudar a realidade atual através de resultados futuros melhores, a esperança parece influenciar o comportamento do consumidor. Com o propósito de avançar no entendimento do tema a presente pesquisa tem o objetivo de avaliar a influência da esperança no consumo de cosméticos anti-sinais. Foram entrevistadas 15 mulheres com idade entre 25 e 30 anos, através da utilização de técnica projetiva. Considerou-se para esta pesquisa a abordagem seguida por MacInnis e Mello (2001; 2005), segundo a qual a esperança é um conceito multidimensional, composto pela congruência dos objetivos com o ambiente, pela orientação para o futuro e pela vontade de ter um objeto específico. Através de seus relatos identificaram-se seis dimensões relacionadas à esperança, compostas por seus aspectos formadores; por emoções e sentimentos que se parecem e se confundem com ela; pela força motivacional para alcance de objetivos e manutenção do empenho; por episódios, fatos e mídias que a provocam; por fatores temporais que a afetam e por sua relação com a beleza. Os resultados indicam que o objetivo final da esperança parece ser a transformação do futuro em algo congruente com o self idealizado, concretizada através da posse e conquista de bens materiais. Neste processo de idealização a imaginação e o desejo desempenham papel importante, pois habilitam o indivíduo a imaginar-se gozando de uma situação futura diferente, apesar da deficiência atual percebida. / Hope is an important emotion in people every day’s life but which has not yet been properly understood by studies of human behavior. Used as sale argument of products that promise to change the current reality through better future results, hope seems to influence also the consumer behavior. With regard to increase the understanding of the subject, this research intended to evaluate the influence of hope in the consumption of anti-aging cosmetic. 15 women, aged between 25 and 30 years, were interviewed through the projective technique. This study followed MacInnis and Mello (2001, 2005) approach, that consider hope a multidimensional concept, composed by the goal congruence, future orientation and yearning. Through this reports six dimensions was identified as related to hope, composed by its former aspects; by emotions and sentiments that looks like and are confused with it; by motivational force to reach the goals and maintaining the commitment; by episodes, facts and media that arousal it; by temporal factors that affect it and their relationship to beauty. The results indicate that the final goal of hope seems to be turning the future into something consistent with the idealized self, realized through conquest and possession of material goods. In the process of idealization imagination and desire play an important role, because seems to enable the person to imagine themselves enjoying a future situation differently, despite the current perceived deficiency.

A esperança é uma emoção importante no dia-a-dia das pessoas, mas que ainda não foi devidamente compreendida pelos estudos do comportamento humano. Utilizada como argumento de vendas de produtos que prometem mudar a realidade atual através de resultados futuros melhores, a esperança parece influenciar o comportamento do consumidor. Com o propósito de avançar no entendimento do tema a presente pesquisa tem o objetivo de avaliar a influência da esperança no consumo de cosméticos anti-sinais. Foram entrevistadas 15 mulheres com idade entre 25 e 30 anos, através da utilização de técnica projetiva. Considerou-se para esta pesquisa a abordagem seguida por MacInnis e Mello (2001; 2005), segundo a qual a esperança é um conceito multidimensional, composto pela congruência dos objetivos com o ambiente, pela orientação para o futuro e pela vontade de ter um objeto específico. Através de seus relatos identificaram-se seis dimensões relacionadas à esperança, compostas por seus aspectos formadores; por emoções e sentimentos que se parecem e se confundem com ela; pela força motivacional para alcance de objetivos e manutenção do empenho; por episódios, fatos e mídias que a provocam; por fatores temporais que a afetam e por sua relação com a beleza. Os resultados indicam que o objetivo final da esperança parece ser a transformação do futuro em algo congruente com o self idealizado, concretizada através da posse e conquista de bens materiais. Neste processo de idealização a imaginação e o desejo desempenham papel importante, pois habilitam o indivíduo a imaginar-se gozando de uma situação futura diferente, apesar da deficiência atual percebida. / Hope is an important emotion in people every day’s life but which has not yet been properly understood by studies of human behavior. Used as sale argument of products that promise to change the current reality through better future results, hope seems to influence also the consumer behavior. With regard to increase the understanding of the subject, this research intended to evaluate the influence of hope in the consumption of anti-aging cosmetic. 15 women, aged between 25 and 30 years, were interviewed through the projective technique. This study followed MacInnis and Mello (2001, 2005) approach, that consider hope a multidimensional concept, composed by the goal congruence, future orientation and yearning. Through this reports six dimensions was identified as related to hope, composed by its former aspects; by emotions and sentiments that looks like and are confused with it; by motivational force to reach the goals and maintaining the commitment; by episodes, facts and media that arousal it; by temporal factors that affect it and their relationship to beauty. The results indicate that the final goal of hope seems to be turning the future into something consistent with the idealized self, realized through conquest and possession of material goods. In the process of idealization imagination and desire play an important role, because seems to enable the person to imagine themselves enjoying a future situation differently, despite the current perceived deficiency.

A esperança é uma emoção importante no dia-a-dia das pessoas, mas que ainda não foi devidamente compreendida pelos estudos do comportamento humano. Utilizada como argumento de vendas de produtos que prometem mudar a realidade atual através de resultados futuros melhores, a esperança parece influenciar o comportamento do consumidor. Com o propósito de avançar no entendimento do tema a presente pesquisa tem o objetivo de avaliar a influência da esperança no consumo de cosméticos anti-sinais. Foram entrevistadas 15 mulheres com idade entre 25 e 30 anos, através da utilização de técnica projetiva. Considerou-se para esta pesquisa a abordagem seguida por MacInnis e Mello (2001; 2005), segundo a qual a esperança é um conceito multidimensional, composto pela congruência dos objetivos com o ambiente, pela orientação para o futuro e pela vontade de ter um objeto específico. Através de seus relatos identificaram-se seis dimensões relacionadas à esperança, compostas por seus aspectos formadores; por emoções e sentimentos que se parecem e se confundem com ela; pela força motivacional para alcance de objetivos e manutenção do empenho; por episódios, fatos e mídias que a provocam; por fatores temporais que a afetam e por sua relação com a beleza. Os resultados indicam que o objetivo final da esperança parece ser a transformação do futuro em algo congruente com o self idealizado, concretizada através da posse e conquista de bens materiais. Neste processo de idealização a imaginação e o desejo desempenham papel importante, pois habilitam o indivíduo a imaginar-se gozando de uma situação futura diferente, apesar da deficiência atual percebida. / Hope is an important emotion in people every day’s life but which has not yet been properly understood by studies of human behavior. Used as sale argument of products that promise to change the current reality through better future results, hope seems to influence also the consumer behavior. With regard to increase the understanding of the subject, this research intended to evaluate the influence of hope in the consumption of anti-aging cosmetic. 15 women, aged between 25 and 30 years, were interviewed through the projective technique. This study followed MacInnis and Mello (2001, 2005) approach, that consider hope a multidimensional concept, composed by the goal congruence, future orientation and yearning. Through this reports six dimensions was identified as related to hope, composed by its former aspects; by emotions and sentiments that looks like and are confused with it; by motivational force to reach the goals and maintaining the commitment; by episodes, facts and media that arousal it; by temporal factors that affect it and their relationship to beauty. The results indicate that the final goal of hope seems to be turning the future into something consistent with the idealized self, realized through conquest and possession of material goods. In the process of idealization imagination and desire play an important role, because seems to enable the person to imagine themselves enjoying a future situation differently, despite the current perceived deficiency.

L’entreprise SEPROSYS est une société spécialisée dans le développement de solutions d'extraction et de séparation de molécules. Au cours de l’année 2011, l’entreprise a développé un procédé innovant de séparation et de purification fractionnée de biomolécules issues de macroalgues marines. Ce travail de thèse a pour objectif de trouver des applications aux fractions extraites selon le procédé d’extraction et de purification de la société SEPROSYS, et en particulier la fraction des polysaccharides sulfatés, dans deux domaines distincts : en pharmaceutique pour leur activité anti-coagulante et en cosmétique pour leur activité anti-âge. La première partie de nos travaux se penche sur le potentiel des polysaccharides sulfatés de macroalgues comme anti-coagulants. Pour cela, des extraits aqueux de différentes macroalgues brunes, rouges et vertes ont été préparés et leur activité anti-coagulante a été mesurée. Les algues présentant le meilleur potentiel ont ensuite été traitées au moyen du procédé SEPROSYS® afin de purifier leurs polysaccharides sulfatés et d’étudier leur activité anti-coagulante. De plus, l’objectif de ce travail consiste également à mieux comprendre la relation structure-fonction de l'activité anticoagulante d'ulvanes. A cette fin, des ulvanes issus d’Ulva sp. de pureté élevée ont été produits par le procédé SEPROSYS®, soumis à des modifications chimique (hypersulfatation) et physique (dépolymérisation) et leur activité anticoagulante a été étudiée. La deuxième partie de nos travaux concerne l’évaluation du potentiel de ces macroalgues comme agents actifs utilisables en dermo-cosmétique, en particulier pour leur activité anti-âge. Dans ce but, différentes fractions de macroalgues brunes, rouges et vertes ont été testées sur des lignées cellulaires de fibroblastes dermiques humains et leur effet sur la production de collagène par ces fibroblastes a été étudié. Enfin, le potentiel d’ulvanes extraits d’Uva sp. par le procédé de l’entreprise SEPROSYS pour stimuler la biosynthèse de collagène et d’acide hyaluronique par ces mêmes fibroblastes a été déterminé. / SEPROSYS is a company specialized in the development of solutions for the extraction and separation of molecules. In 2011, the company has developed an innovative process of fractionated separation and purification of biomolecules from macroalgae. The purpose of this thesis work is to find applications for the purified fractions from the SEPROSYS® process and in particular the sulfated polysaccharides, for two distinct biological activities : as pharmaceutical for their anti-coagulant activity and as dermo-cosmetics for their anti-aging activity. The first part of our work focus on the potential of sulfated polysaccharides from macroalgae as anti-coagulant agents. To this end, aqueous extracts from brown, red and green macroalgae were prepared and their anti-coagulant activity was measured. The best macroalgae were then processed with the SEPROSYS procedure in order to purify the sulfated polysaccharides and study their activity. Furthermore, one of the objectives of this work was to acquire a better understanding of the structure/anti-coagulant function relationship of ulvans. Ulvans of high purity were extracted from Ulva sp. with the SEPROSYS® process, submitted to chemical (hypersulfatation) and physical (depolymerization) modifications and their anti-coagulant activity was measured. The second part of our work relates to the potential of the macroalgae as active agents to be used in dermo-cosmetics, and, in particular, for their anti-aging activity. Different brown, red and green macroalgae fractions were thus tested on normal human dermal fibroblasts cell lines and their effects on the collagen production were measured. Furthermore, the capacity of different molecular weight ulvans extracted from Ulva sp. to stimulate the collagen and hyaluronan biosynthesis was studied. To this end, we developed an efficient depolymerization procedure using ion exchange resins.

<p>Aging erodes motivation, cognition, sensory modalities and physical capacities, effectively depleting quality of life. Declining sensory, cognitive and motor function are reliable biomarkers of aging and mortality risk. These declines are associated with dysregulation of systemic and cellular processes. We developed a complex dietary supplement (DSP) designed to ameliorate five mechanisms of aging (oxidative processes, inflammation, mitochondrial function, insulin resistance and membrane integrity). Remarkably, normal mice fed the DSP retained youthful functionality into old ages, reflecting slower aging rates. Marked improvements in motor function, memory capacity, spatial learning, muscle strength, visual acuity, olfaction, fecundity and important behavioral functions were observed in aging supplemented mice. Conversely, untreated control animals showed age-related declines in all of the above. Functional improvements were associated with reduced oxidative damage, elevated mitochondrial activity, positive cellular energy balance, improved glucose tolerance, boosted neurotransmitters, greater synaptic density and higher neuronal numbers throughout the brain. A 30% reduction in cancer rates was also documented for DSP treated p53+/- mice. The vast functional benefits greatly exceed the modest longevity extension (11%) in normal supplemented mice. For aging humans, maintaining functionality and performance into later years may provide greater socioeconomic and health benefits than simply prolonging lifespan. Implications of these findings extend to common age-related pathologies including dementia and neurodegenerative diseases, diabetes, cancer, sarcopenia and age-related macular degeneration. Although identifying the role of specific ingredients remains outstanding, results provide proof of principle that complex dietary cocktails can powerfully ameliorate biomarkers of aging and modulate mechanisms considered ultimate goals for aging interventions.</p> / Doctor of Philosophy (PhD)