Stress responses, vitagenes and hormesis as critical determinants in aging and longevity: Mitochondria as a "chi".
Stress responses, vitagenes and hormesis as critical determinants in aging and longevity: Mitochondria as a "chi".
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DOI：
10.1186/1742-4933-10-15
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发表时间：
2013-04-25
期刊：
影响因子：
--
通讯作者：
Calabrese V
中科院分区：
文献类型：
--
作者：
Cornelius C;Perrotta R;Graziano A;Calabrese EJ;Calabrese V
了解衰老的机制和寿命的决定因素将有助于减少与年龄相关的发病率，促进健康老龄化。在过去的几个世纪里，由于医疗和环境因素，平均寿命有所增加，但最长寿命保持不变。目前，在动物模型中，通过遗传操作和热量限制（CR）等措施可以延长最大寿命。CR似乎通过减少活性氧（ROS）介导的氧化损伤来延长生命。但是，ROS的形成，这是积极参与细胞应激反应机制，是一个高度调节的过程控制的复杂网络的细胞内信号通路。通过感知细胞内的营养和能量状态、线粒体的功能状态以及线粒体中产生的ROS的浓度，长寿网络通过协调沿着其会聚、发散和多分支信号通路的信息流来调节跨物种的寿命，包括维生素基因，其是在应激条件下参与保持细胞稳态的基因。维生素基因编码热休克蛋白（Hsp）Hsp 32、Hsp 70、硫氧还蛋白和沉默调节蛋白蛋白系统。膳食抗氧化剂，最近已被证明是通过激活激素途径，包括维生素的神经保护。兴奋性剂量-反应挑战了长期以来关于低剂量区剂量-反应性质的信念，有可能显著影响临床前研究和临床试验的设计以及治疗多种疾病的最佳患者剂量的策略。鉴于热休克反应的广泛细胞保护特性，现在人们对发现和开发能够诱导应激反应的药理学药物产生了浓厚的兴趣。在这里，我们专注于可能的信号转导机制参与激活的维生素，导致增强防御能量和抗应激稳态破坏，从而对长寿过程的影响。
Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR). CR appears to prolong life by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways. By sensing the intracellular nutrient and energy status, the functional state of mitochondria, and the concentration of ROS produced in mitochondria, the longevity network regulates life span across species by coordinating information flow along its convergent, divergent and multiply branched signaling pathways, including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, challenges long-standing beliefs about the nature of the dose–response in a lowdose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysiruption with consequent impact on longevity processes.
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DOI：
10.1074/jbc.m110.157552
发表时间：
2010-11-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Akerfelt M;Vihervaara A;Laiho A;Conter A;Christians ES;Sistonen L;Henriksson E
通讯作者：
Henriksson E
影响因子：
6.6
作者：
Calabrese, Vittorio;Sultana, Rukhsana;Butterfield, D. A.
通讯作者：
Butterfield, D. A.
DOI：
10.1165/rcmb.2006-0340tr
发表时间：
2007-02-01
影响因子：
6.4
作者：
Alam, Jawed;Cook, Julia L.
通讯作者：
Cook, Julia L.
DOI：
10.1016/j.bbadis.2011.12.003
发表时间：
2012-05-01
影响因子：
6.2
作者：
Calabrese, V.;Cornelius, C.;Castellino, P.
通讯作者：
Castellino, P.
影响因子：
2.8
作者：
Calabrese, Edward J.;Mattson, Mark P.;Calabrese, Vittorio
通讯作者：
Calabrese, Vittorio