Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.
Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.
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DOI：
10.2337/db15-0291
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发表时间：
2016-06
期刊：
影响因子：
7.7
通讯作者：
LeBrasseur NK
中科院分区：
文献类型：
--
作者：
Schafer MJ;White TA;Evans G;Tonne JM;Verzosa GC;Stout MB;Mazula DL;Palmer AK;Baker DJ;Jensen MD;Torbenson MS;Miller JD;Ikeda Y;Tchkonia T;van Deursen JM;Kirkland JL;LeBrasseur NK
相当多的证据表明细胞衰老与衰老和慢性疾病的生物学有关。饮食和锻炼是健康衰老的决定因素;然而，它们在多大程度上影响不同组织中衰老细胞的行为和增长尚不清楚。在这里，我们测试的假设，运动防止过早衰老细胞积累和系统性代谢功能障碍诱导的快餐饮食（FFD）。使用转基因小鼠，表达绿色荧光蛋白响应激活衰老相关的p16 INK 4a启动子，我们证明，FFD消费导致有害的变化，体重和组成，以及在身体，心脏和代谢健康的措施。FFD的有害影响与几种衰老标志物的急剧增加有关，包括p16、EGFP、衰老相关β-半乳糖苷酶和衰老相关分泌表型（SASP），特别是在内脏脂肪组织中。我们发现，运动可以防止衰老细胞的积累和SASP的表达，同时消除FFD对健康参数的破坏性影响。我们还证明，长期FFD喂养后开始的运动减少了内脏脂肪组织中的衰老表型标志物，同时减轻了身体损伤，这表明运动可能通过减轻累积的衰老负担提供恢复性益处。这些发现强调了一种新的机制，通过这种机制，运动可以调节其有益效果，并加强可改变的生活方式选择对健康寿命的影响。
Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16INK4a promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span.