Innate sensitivity to stress facilitates inflammation, alters metabolism and shortens lifespan in a mouse model of social hierarchy
Innate sensitivity to stress facilitates inflammation, alters metabolism and shortens lifespan in a mouse model of social hierarchy
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DOI：
10.18632/aging.102440
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发表时间：
2019-11-15
期刊：
影响因子：
5.2
通讯作者：
Pinhasov, Albert
中科院分区：
文献类型：
--
作者：
Bairachnaya, Maryia;Agranyoni, Oryan;Pinhasov, Albert
众所周知，压力会改变体内平衡，并可能导致加速衰老。然而，对应激的先天易感性在生理功能恶化、加速衰老和与年龄相关疾病的发生中的作用却知之甚少。通过使用社会顺从应激敏感（Sub）和社会主导应激弹性（Dom）选择性繁殖的小鼠模型，我们观察到雄性和雌性Sub小鼠的寿命显著减少。我们发现，先天性应激易感性与慢性炎症、脾肿大的发展以及循环促炎细胞因子IL-1 β和IL-6水平的显著增加相关。此外，Sub小鼠表现出明显的低血糖、胰岛素水平降低、GSK 3活性增加和IGF-1血清水平升高，以及皮肤表面温度和体重降低。有趣的是，Sub小鼠终身暴露于慢性轻度应激并没有进一步缩短其寿命，这表明内在应激水平很高。总之，我们的数据显示，社会顺从加上先天的压力敏感性与炎症相吻合，导致生理功能的恶化和早期衰老，而与个体是否暴露于压力无关。
It is known that stress alters homeostasis and may lead to accelerated aging. However, little is known about the contribution of innate susceptibility to stress to the deterioration of physiological functions, acceleration of aging and developing of age-related diseases. By using socially-submissive stress susceptible (Sub) and socially-dominant stress resilient (Dom) selectively bred mouse model we observed a marked reduction in the lifespan of both male and female Sub mice. We found that innate susceptibility to stress correlates with chronic inflammation, development of splenomegaly and a significant increase in the levels of circulating proinflammatory cytokines IL-1 beta and IL-6. Furthermore, Sub mice showed a marked hypoglycemia, reduction of insulin levels, increase in GSK3 activity and elevation of IGF-1 serum levels, as well as low skin surface temperature and body weight. Interestingly, lifelong exposure of Sub mice to chronic mild stress did not further reduce their lifespan, indicating a high level of intrinsic stress. Taken together, our data reveal that social submissiveness coupled with innate stress sensitivity coincides with inflammation, leading to the deterioration of physiological functions and early aging independent of whether an individual is exposed to stress or not.