Social stress shortens lifespan in mice.
Social stress shortens lifespan in mice.
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DOI：
10.1111/acel.12778
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发表时间：
2018-08
期刊：
影响因子：
7.8
通讯作者：
Bartolomucci A
中科院分区：
文献类型：
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作者：
Razzoli M;Nyuyki-Dufe K;Gurney A;Erickson C;McCallum J;Spielman N;Marzullo M;Patricelli J;Kurata M;Pope EA;Touma C;Palme R;Largaespada DA;Allison DB;Bartolomucci A
人类的压力和较低的社会经济地位增加了发病率和死亡率的脆弱性。然而，这种关联并没有被机械地理解，也没有在动物模型中探索其因果关系。最近，细胞衰老被认为是将终身压力与年龄相关疾病和人类预期寿命缩短联系起来的潜在机制。在这里，我们建立了终身社会压力对缩短寿命和增加小鼠心血管疾病风险的因果关系。具体来说，我们开发了一个终身慢性心理社会压力模型，其中雄性小鼠的攻击行为用于研究负面社会对抗对健康和寿命的影响。通过无偏聚类分析鉴定为接受高攻击性而表现出低攻击性的C57 BL/6 J小鼠，或基于行为学标准鉴定为从属的C57 BL/6 J小鼠，具有较低的中位寿命和最长寿命，并且在存在细胞衰老特征的情况下发展出较早的几种器官病理学发作。重要的是，从属小鼠出现自发性早期主动脉窦动脉粥样硬化病变，特征为显著的免疫细胞浸润和散发性破裂和钙化，在优势受试者中未发现这些病变。总之，我们在这里提出了第一个啮齿动物模型来研究和机械解剖慢性应激对寿命和衰老疾病的影响。这些数据强调了社会压力和社会地位低下对哺乳动物寿命缩短和心血管疾病风险增加的保守作用，并确定了这种复杂现象的潜在机制联系。
Stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality. However, this association is not mechanistically understood nor has its causation been explored in animal models thus far. Recently, cellular senescence has been suggested as a potential mechanism linking lifelong stress to age‐related diseases and shorter life expectancy in humans. Here, we established a causal role for lifelong social stress on shortening lifespan and increasing the risk of cardiovascular disease in mice. Specifically, we developed a lifelong chronic psychosocial stress model in which male mouse aggressive behavior is used to study the impact of negative social confrontations on healthspan and lifespan. C57BL/6J mice identified through unbiased cluster analysis for receiving high while exhibiting low aggression, or identified as subordinate based on an ethologic criterion, had lower median and maximal lifespan, and developed earlier onset of several organ pathologies in the presence of a cellular senescence signature. Critically, subordinate mice developed spontaneous early‐stage atherosclerotic lesions of the aortic sinuses characterized by significant immune cells infiltration and sporadic rupture and calcification, none of which was found in dominant subjects. In conclusion, we present here the first rodent model to study and mechanistically dissect the impact of chronic stress on lifespan and disease of aging. These data highlight a conserved role for social stress and low social status on shortening lifespan and increasing the risk of cardiovascular disease in mammals and identify a potential mechanistic link for this complex phenomenon.
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DOI：
10.1001/jama.2016.4226
发表时间：
2016-04-26
期刊：
JAMA
影响因子：
--
作者：
Chetty R;Stepner M;Abraham S;Lin S;Scuderi B;Turner N;Bergeron A;Cutler D
通讯作者：
Cutler D
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
4.3
作者：
Bartolomucci, Alessandro;Carola, Valeria;Gross, Cornelius
通讯作者：
Gross, Cornelius
影响因子：
2.4
作者：
Brayton, C. F.;Treuting, P. M.;Ward, J. M.
通讯作者：
Ward, J. M.
影响因子：
82.9
作者：
通讯作者：
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