Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control.
Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control.
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DOI：
10.1111/febs.15631
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Jansen-Dürr P
中科院分区：
文献类型：
--
作者：
Cavinato M;Madreiter-Sokolowski CT;Büttner S;Schosserer M;Zwerschke W;Wedel S;Grillari J;Graier WF;Jansen-Dürr P
细胞衰老是由严重损伤和压力引起的稳定的细胞分裂停滞，是人类衰老的标志。在这里，我们回顾了与线粒体及其细胞器间通讯有关的衰老机制，以及衰老表型中蛋白质稳态网络和代谢控制的参与。我们还探讨了以这些机制为目标的可能性，作为以组织年轻化为目的的药理学干预的新机会。 细胞衰老是由严重损伤和压力引起的稳定的细胞分裂停滞，是包括人类在内的脊椎动物衰老的标志。随着年龄的增长，衰老细胞在各种哺乳动物组织中积累，在那里它们有助于组织衰老，将细胞衰老确定为延迟或预防衰老的主要目标。对于发现新类型的小分子的需求日益增加，所述小分子将通过从身体中选择性地消除衰老细胞来避免或推迟细胞衰老（即，“senolytics”）或灭活/转换衰老细胞的损伤诱导性质（即，“衰老抑制剂/衰老形态学”），如衰老相关的分泌表型。尽管已经描述了具有衰老清除或衰老抑制活性的化合物，但它们的功效和特异性尚未完全确定用于临床用途。在这里，我们回顾了与线粒体及其细胞器间通讯有关的衰老机制，以及衰老表型中蛋白质稳态网络和代谢控制的参与。这些细胞功能在体外和体内模型中与细胞衰老相关，但尚未被充分利用来寻找新的化合物来对抗衰老。因此，我们探索了以这些机制为目标的可能性，作为选择性消除和/或禁用衰老细胞的新机会，目的是组织再生。我们假设这项研究将提供来自化学空间的新化合物，其作为热量限制的模拟物，钙信号传导和线粒体生理学的调节剂，或作为蛋白质稳态优化剂，具有对抗细胞衰老的潜力，从而允许健康衰老。
Cellular senescence, a stable cell division arrest caused by severe damage and stress, is a hallmark of aging in humans. Here, we review mechanisms of senescence that are related to mitochondria and their interorganelle communication, and the involvement of proteostasis networks and metabolic control in the senescent phenotype. We also explore possibilities to target these mechanisms as new opportunities for pharmacological interventions with the aim of tissue rejuvenation. Cellular senescence, a stable cell division arrest caused by severe damage and stress, is a hallmark of aging in vertebrates including humans. With progressing age, senescent cells accumulate in a variety of mammalian tissues, where they contribute to tissue aging, identifying cellular senescence as a major target to delay or prevent aging. There is an increasing demand for the discovery of new classes of small molecules that would either avoid or postpone cellular senescence by selectively eliminating senescent cells from the body (i.e., ‘senolytics’) or inactivating/switching damage‐inducing properties of senescent cells (i.e., ‘senostatics/senomorphics’), such as the senescence‐associated secretory phenotype. Whereas compounds with senolytic or senostatic activity have already been described, their efficacy and specificity has not been fully established for clinical use yet. Here, we review mechanisms of senescence that are related to mitochondria and their interorganelle communication, and the involvement of proteostasis networks and metabolic control in the senescent phenotype. These cellular functions are associated with cellular senescence in in vitro and in vivo models but have not been fully exploited for the search of new compounds to counteract senescence yet. Therefore, we explore possibilities to target these mechanisms as new opportunities to selectively eliminate and/or disable senescent cells with the aim of tissue rejuvenation. We assume that this research will provide new compounds from the chemical space which act as mimetics of caloric restriction, modulators of calcium signaling and mitochondrial physiology, or as proteostasis optimizers, bearing the potential to counteract cellular senescence, thereby allowing healthy aging.
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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
DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
影响因子：
64.5
作者：
de Cabo R;Carmona-Gutierrez D;Bernier M;Hall MN;Madeo F
通讯作者：
Madeo F
DOI：
10.1083/jcb.201602069
发表时间：
2016-09-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Das A;Nag S;Mason AB;Barroso MM
通讯作者：
Barroso MM
影响因子：
8.8
作者：
Alupei, Marius Costel;Maity, Pallab;Iben, Sebastian
通讯作者：
Iben, Sebastian