Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity
Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity
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DOI：
10.1093/gerona/glu055
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发表时间：
2014-06-01
影响因子：
5.1
通讯作者：
Lithgow, Gordon J.
中科院分区：
文献类型：
--
作者：
Epel, Elissa S.;Lithgow, Gordon J.
生物衰老的速度在一定程度上是由与应激源暴露相互作用的基因调节的。基础研究表明，暴露在短期压力下可以增强细胞对压力的反应(“精神压力”)。应激延长寿命的部分原因是通过增强分子伴侣的活性和其他防御机制。相反，长期暴露在压力下会压倒代偿性反应(“毒性压力”)，缩短寿命。一个关键的问题是，在衰老的基本模型中被充分理解的压力源是否能够帮助我们理解心理压力源和人类健康。心理应激反应促进了衰老过程中重要的调节变化(例如，应激激素、炎症、氧化应激、胰岛素的增加)。严重压力的负面影响在人类身上得到了很好的证明。对急性应激(抗应激)的潜在积极影响的研究较少，特别是在细胞水平上。应激抵抗能否减缓人类的衰老速度，就像在模型生物中所做的那样？如果是这样的话，我们如何提高人类的抗应激能力？我们敦促一个新的研究议程，包括从细胞压力到心理压力的连续体，同时使用基础研究和人类研究。这将需要跨学科的新方法，这些方法在理解和干预人类慢性病方面充满希望。
The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e. g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease.