Senescence under appraisal: hopes and challenges revisited.
Senescence under appraisal: hopes and challenges revisited.
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DOI：
10.1007/s00018-020-03746-x
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Montero-Melendez T
中科院分区：
文献类型：
--
作者：
Davan-Wetton CSA;Pessolano E;Perretti M;Montero-Melendez T
近年来，细胞衰老已成为生物医学研究多个领域关注的焦点。细胞衰老通常被定义为不可逆的细胞周期停滞，伴随着增加的细胞生长、代谢活性和特征性的信息传递分泌组，细胞衰老可以影响多种生理和病理过程，如伤口愈合、纤维化、癌症和衰老。这些被不公正地称为“僵尸细胞”的细胞确实是创新治疗发展的丰富机会来源。在这篇综述中，我们整理了目前对细胞衰老过程及其两面性的理解，即有益/有害，并将这种二元性与上下文方面联系起来。我们提出衰老程序作为一种内源性促消退机制，当失调或衰老细胞未被有效清除时，可能导致持续的炎症和损伤。这个亲解决模型通过强调导致病理的是程序的不成功完成，而不是衰老本身，来调和衰老的矛盾两面。因此，在正确的情况下，促衰老疗法可能有利于炎症消退。我们还审查了基于衰老的多种治疗方法的证据，包括其诱导，预防，清除以及使用衰老药物和senomorphic药物。特别是，我们强调了免疫系统在衰老的有利结果中的重要性，以及在完成衰老周期中无效的免疫监视的影响。最后，我们确定并讨论了一些挑战和现有的差距，以鼓励和刺激在这个令人兴奋和解开领域的进一步研究，希望促进和加速基于衰老的疗法的临床成功。
In recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest accompanied by increased cellular growth, metabolic activity and by a characteristic messaging secretome, cellular senescence can impact on multiple physiological and pathological processes such as wound healing, fibrosis, cancer and ageing. These unjustly called ‘zombie cells’ are indeed a rich source of opportunities for innovative therapeutic development. In this review, we collate the current understanding of the process of cellular senescence and its two-faced nature, i.e. beneficial/detrimental, and reason this duality is linked to contextual aspects. We propose the senescence programme as an endogenous pro-resolving mechanism that may lead to sustained inflammation and damage when dysregulated or when senescent cells are not cleared efficiently. This pro-resolving model reconciles the paradoxical two faces of senescence by emphasising that it is the unsuccessful completion of the programme, and not senescence itself, what leads to pathology. Thus, pro-senescence therapies under the right context, may favour inflammation resolution. We also review the evidence for the multiple therapeutic approaches under development based on senescence, including its induction, prevention, clearance and the use of senolytic and senomorphic drugs. In particular, we highlight the importance of the immune system in the favourable outcome of senescence and the implications of an inefficient immune surveillance in completion of the senescent cycle. Finally, we identify and discuss a number of challenges and existing gaps to encourage and stimulate further research in this exciting and unravelled field, with the hope of promoting and accelerating the clinical success of senescence-based therapies.
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影响因子：
16.6
作者：
Cazier, J. -B.;Rao, S. R.;McLean, C. M.;Walker, A. L.;Wright, B. J.;Jaeger, E. E. M.;Kartsonaki, C.;Marsden, L.;Yau, C.;Camps, C.;Kaisaki, P.;Taylor, J.;Catto, J. W.;Tomlinson, I. P. M.;Kiltie, A. E.;Hamdy, F. C.
通讯作者：
Hamdy, F. C.
DOI：
10.18632/aging.100281
发表时间：
2011-02
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV
通讯作者：
Blagosklonny MV
影响因子：
14.5
作者：
Antonio Gomez-Sanchez, Jose;Gomis-Coloma, Clara;Cabedo, Hugo
通讯作者：
Cabedo, Hugo
影响因子：
6.2
作者：
Chandra, Abhishek;Lagnado, Anthony B.;Pignolo, Robert J.
通讯作者：
Pignolo, Robert J.
影响因子：
10.5
作者：
Bent EH;Gilbert LA;Hemann MT
通讯作者：
Hemann MT