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Caloric Restriction and Consequences in Metabolism
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Resumo(s)
A restrição calórica (RC) pode contribuir para melhorar múltiplos processos metabólicos, gerando benefícios em todo o organismo. Neste contexto, o potencial atraso na progressão do envelhecimento e no desenvolvimento de doenças relacionadas à idade têm sido amplamente estudados. Para explicar o processo de envelhecimento, a “teoria mitocondrial do envelhecimento” é considerada como um dos conceitos mais promissores, que estabelece uma relação estreita entre o comprometimento da mitocôndria e a consequente produção e acumulação de espécies reativas de oxigénio (ROS). Vários estudos sugerem que uma melhoria na função mitocondrial induzida por RC está relacionada com um aumento na biogénese e turnover mitocondrial. A presente monografia resume os principais mecanismos bioquímicos associados à RC e tem como objetivo principal rever os trabalhos científicos mais significativos sobre as inerentes consequências para o metabolismo mitocondrial. Esta revisão irá focar-se no papel da RC na promoção da saúde, modulando vias cruciais associadas à biogénese mitocondrial. Estes processos são controlados por AMPK, sirtuinas, IGF-1, TOR e PGC-1α, levando a uma menor produção endógena de ROS. No entanto, nos últimos anos, alguns riscos para o Homem associados à RC e à implementação de dietas drásticas a longo prazo, foram também estabelecidos. A pesquisa de compostos alternativos mais seguros e práticos, conhecidos como “miméticos de RC”, tem vindo a desenvolver-se. A metformina, rapamicina e resveratrol constituem exemplos entre os compostos mais promissores, com potencialidades para futura aplicação terapêutica. Por este motivo, os mecanismos subjacentes aos benefícios fisiológicos dos miméticos de RC também serão abordados no âmbito deste trabalho.
Caloric restriction (CR) may contribute for improving multiple metabolic processes, generating benefits throughout the whole organism. In this context, the potential delay of ageing progression and of development of age-related diseases has been widely studied. To explain the ageing process, the “mitochondrial theory of aging” is regarded as one of the most promising concept, which establishes a link between an impairment of mitochondria and consequent production and accumulation of ROS. Several studies suggest that improvements in mitochondrial function induced by CR are related with an increase in mitochondrial biogenesis and turnover. The present monograph summarizes the main biochemical mechanisms associated with CR and aims to review the major research reports concerning the respective consequences to mitochondrial metabolism. This review will focus on CR-dependent role on health promotion by modulating crucial pathways associated with mitochondrial biogenesis. These are controlled by AMPK, sirtuins, IGF-1, TOR and PGC-1α, leading to lower endogenous ROS production. However in recent years, some risks associated with CR and with implementation of long-term severe diets in humans have been defined. The search for safer and more practical alternative compounds, known as “CR mimetics”, has emerged. Metformin, rapamycin and resveratrol are examples among the most promising compounds, with potential for future therapeutic application. Therefore, the mechanisms underlying the physiological benefits of CR mimetics will also be reviewed in present work.
Caloric restriction (CR) may contribute for improving multiple metabolic processes, generating benefits throughout the whole organism. In this context, the potential delay of ageing progression and of development of age-related diseases has been widely studied. To explain the ageing process, the “mitochondrial theory of aging” is regarded as one of the most promising concept, which establishes a link between an impairment of mitochondria and consequent production and accumulation of ROS. Several studies suggest that improvements in mitochondrial function induced by CR are related with an increase in mitochondrial biogenesis and turnover. The present monograph summarizes the main biochemical mechanisms associated with CR and aims to review the major research reports concerning the respective consequences to mitochondrial metabolism. This review will focus on CR-dependent role on health promotion by modulating crucial pathways associated with mitochondrial biogenesis. These are controlled by AMPK, sirtuins, IGF-1, TOR and PGC-1α, leading to lower endogenous ROS production. However in recent years, some risks associated with CR and with implementation of long-term severe diets in humans have been defined. The search for safer and more practical alternative compounds, known as “CR mimetics”, has emerged. Metformin, rapamycin and resveratrol are examples among the most promising compounds, with potential for future therapeutic application. Therefore, the mechanisms underlying the physiological benefits of CR mimetics will also be reviewed in present work.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
Restrição calórica ROS Biogénese mitocondrial AMPK Sirtuinas IGF-1 TOR PGC-1α Miméticos de restrição calórica Metformina Rapamicina Resveratrol Mestrado Integrado - 2019