Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice.
Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice.
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DOI：
10.1111/acel.13208
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发表时间：
2020-09
期刊：
影响因子：
7.8
通讯作者：
Geiger H
中科院分区：
文献类型：
--
作者：
Florian MC;Leins H;Gobs M;Han Y;Marka G;Soller K;Vollmer A;Sakk V;Nattamai KJ;Rayes A;Zhao X;Setchell K;Mulaw M;Wagner W;Zheng Y;Geiger H
Cdc42是一种在真核细胞中调节多种功能的小RhoGTPase。Cdc42的活性在老年小鼠的几种组织中显著升高，而Cdc42活性增加小鼠模型呈现出早衰样表型和寿命缩短。这些数据表明Cdc42活性升高、衰老和寿命缩短之间存在因果关系。在这里，我们证明了用Cdc42活性特异性抑制剂（CASIN）连续4天全身治疗老年（75周龄）雌性C57BL/6小鼠可显著延长平均寿命和最长寿命。此外，衰老的CASIN处理的动物血清中显示出与衰老相关的细胞因子IL - 1β、IL - 1α和INFγ的年轻水平，并且基于血细胞中的DNA甲基化水平，表观遗传时钟明显更年轻。总的来说，我们的数据表明，在老年小鼠中，全身给予CASIN以降低Cdc42活性可以延长小鼠的寿命。小RhoGTPase Cdc42的活性在老年人血液和老年小鼠的几种组织中显著升高。Cdc42构成激活诱导小鼠早衰，降低小鼠寿命。在这里，我们展示了连续4天用Cdc42活性特异性抑制剂（CASIN）全身治疗老年（75周龄）雌性C57BL/6小鼠，显著延长平均寿命和最长寿命，降低血清中IL - 1b、IL - 1a和INFg衰老相关细胞因子的水平，并恢复基于血细胞DNA甲基化水平的生物表观遗传时钟。
Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain‐of‐activity mouse model presents with a premature aging‐like phenotype and with decreased lifespan. These data suggest a causal connection between elevated activity of Cdc42, aging, and reduced lifespan. Here, we demonstrate that systemic treatment of aged (75‐week‐old) female C57BL/6 mice with a Cdc42 activity‐specific inhibitor (CASIN) for 4 consecutive days significantly extends average and maximum lifespan. Moreover, aged CASIN‐treated animals displayed a youthful level of the aging‐associated cytokines IL‐1β, IL‐1α, and INFγ in serum and a significantly younger epigenetic clock as based on DNA methylation levels in blood cells. Overall, our data show that systemic administration of CASIN to reduce Cdc42 activity in aged mice extends murine lifespan. The activity of the small RhoGTPase Cdc42 is significantly elevated in blood of elderly humans and in several tissues of aged mice. Cdc42 constitutive activation induces premature aging and decreases murine lifespan. Here, we show that systemic treatment of aged (75‐week‐old) female C57BL/6 mice with a Cdc42 activity‐specific inhibitor (CASIN) for 4 consecutive days significantly extends average and maximum lifespan, reduces levels of IL‐1b, IL‐1a, and INFg aging‐associated cytokines in serum, and rejuvenates the biological epigenetic clock as based on DNA methylation levels in blood cells.
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影响因子：
12.3
作者：
Grigoryan A;Guidi N;Senger K;Liehr T;Soller K;Marka G;Vollmer A;Markaki Y;Leonhardt H;Buske C;Lipka DB;Plass C;Zheng Y;Mulaw MA;Geiger H;Florian MC
通讯作者：
Florian MC
DOI：
10.4049/jimmunol.1003049
发表时间：
2011-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Goswami R;Kaplan MH
通讯作者：
Kaplan MH
影响因子：
23.9
作者：
Florian, Maria Carolina;Doerr, Karin;Niebel, Anja;Daria, Deidre;Schrezenmeier, Hubert;Rojewski, Markus;Filippi, Marie-Dominique;Hasenberg, Anja;Gunzer, Matthias;Scharffetter-Kochanek, Karin;Zheng, Yi;Geiger, Hartmut
通讯作者：
Geiger, Hartmut
影响因子：
10.1
作者：
Brown, Andreas;Schuetz, Desiree;Geiger, Hartmut
通讯作者：
Geiger, Hartmut
影响因子：
9.8
作者：
Florian MC;Klose M;Sacma M;Jablanovic J;Knudson L;Nattamai KJ;Marka G;Vollmer A;Soller K;Sakk V;Cabezas-Wallscheid N;Zheng Y;Mulaw MA;Glauche I;Geiger H
通讯作者：
Geiger H