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    • "Several studies found that mitochondrial biogenesis is impaired during ageing, especially in high-energy-demanding tissues such as muscle, brain or heart (Conley et al. 2000;Short et al. 2005). CR and other interventions such as exercise or nutraceuticals such as resveratrol induce mitochondrial biogenesis in heart and skeletal muscle in humans and other organisms (Feige et al. 2008;Baur et al. 2010;Rodriguez-Bies et al. 2015), indicating their role in the maintenance of the mitochondrial activity in these organs during ageing. At least three different pathways have been associated with this effect on mitochondrial biogenesis in muscle: eNOS induction, PGC-1α activation and adiponectin-dependent activation of the SIRT1/AMPK axis. "
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    ABSTRACT: Ageing causes loss of functions in tissues and organs, is accompanied by a chronic inflammatory process and affects life and health span. Calorie restriction (CR) is a non-genetic intervention that prevents age-associated diseases and extends longevity in most of the animal models studied so far. CR produces a pleiotropic effect and improves multiple metabolic pathways leading generating benefits to the whole organism. Among the effects of CR, modulation of the mitochondrial activity and decrease of oxidative damage are two of the hallmarks. Oxidative damage is reduced by the induction of endogenous antioxidant systems and modulation of the peroxidability index in cell membranes. Mitochondrial activity changes are regulated by inhibition of IGF-1 and TOR-dependent activities and activation of AMPK and the sirtuin family of proteins Activity of PGC-1α and FoxO is regulated by these systems and involved in mitochondria biogenesis, oxidative metabolism activity and mitochondrial turnover. The use of mimetics and the regulation of common factors have demonstrated that these molecular pathways are essential to explain the effect of CR in the organism. Finally, the anti-inflammatory effect of CR is an interesting emerging factor to be taken into consideration. In the present revision we focus on the general effect of CR and other mimetics in longevity focusing especially on cardiovascular system and skeletal muscle. This article is protected by copyright. All rights reserved.
    Preview · Article · Nov 2015 · The Journal of Physiology
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    • "The founding member of the sirtuin family is the yeast gene SIR2 (silent information regulator 2), a histone deacetylase involved in regulating gene silencing through chromatin remodelling. SIR2 and its homologues play a role in lifespan regulation in yeast, worms, and flies, although its role in CR has been somewhat controversial (Baur et al., 2010; Fontana et al., 2010). There are seven mammalian sirtuins (SIRT1–7) that are functionally nonredundant and partitioned to distinct subcellular compartments. "
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    ABSTRACT: Caloric restriction (CR) is a dietary intervention that robustly extends lifespan in diverse species. In mammals CR extends the period in which the animal is fit and vig-orous, and attenuates age-related disease vulnerability. Benefits of CR include reduced incidence of cancer, improved cardiovascular health, increased insulin sensi-tivity, and resistance to neurodegenerative diseases. The fact that CR extends not only average lifespan but also maximum lifespan has led to the consensus that an opti-mised CR diet slows the aging process itself. Here we outline the effects of CR on physiology and metabolism and where these may fit with current theories of aging. The authors describe factors that are likely to mediate the physiological adaptations to CR, placing an emphasis on nutrient sensitive regulators of metabolism. A major incentive for research into the mechanisms of CR is the promise of novel treatments for age-related diseases and disorders that are relevant to human aging.
    Full-text · Article · Oct 2014
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    • "target of rapamycin ) pathways , seem to respond to CR in the control of cell growth and ageing pathways ( Speakman and Mitchell , 2011 ) . In addition , some authors have suggested the involvement of Sirtuins , a group of NAD - dependent histone acetylase , but their role in linking CR to longevity is , at least in mammals , still controversial ( Baur et al . , 2010 ; Fontana et al . , 2010b ) . It is worth to note that both mTOR ( Grummt and Voit , 2010 ; Murayama et al . , 2008 ) and Sirt - 1 ( Salminen and Kaarnir - anta , 2009 ) link the cellular energy condition with the epigenetic status of ribosomal DNA , which in turn plays a role in longevity in model organisms ( Larson et al . , 2012 ) ."
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    ABSTRACT: The rapid technological advancements achieved in the last years have boosted the progressive identification of age-associated epigenetic changes. These studies not only contribute to shed light on the molecular basis of ageing and age-related diseases but, given the plasticity of epigenetic modifications, also provide the basis for anti-ageing interventions to counteract the onset of age-related diseases. In this review we will discuss nutritional interventions as a promising approach that can positively counteract epigenetic changes associated with ageing and promote the health for the elderly. First, we will give an overview of age-associated epigenetic signatures, focusing on DNA methylation. Then, we will report recent evidences regarding the epigenetic changes induced by nutritional interventions in the adulthood (referred as "epigenetic diets"), such as i) caloric/dietary restriction, ii) diet supplementation with nutrients involved in one-carbon metabolism and iii) diet supplementation with bioactive food components. Attention will be drawn on the limits of current studies and the need of proper human models, such as those provided by the ongoing European project NU-AGE. Finally, we will discuss the potential impact of epigenetic diets on inflammaging and age-related diseases, focusing on cardiovascular disease, highlighting the involvement of epigenetic modifications other than DNA methylation, such as microRNA.
    Full-text · Article · Jan 2014 · Mechanisms of ageing and development
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