Therapeutic Opportunities Presented by Modulation of Cellular Senescence.
Therapeutic Opportunities Presented by Modulation of Cellular Senescence.
复制标题
细胞衰老调节带来的治疗机会。
DOI：
10.1007/978-3-031-21410-3_8
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发表时间：
2023
影响因子：
--
通讯作者：
Faragher RGA
中科院分区：
文献类型：
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作者：
Faragher RGA
细胞衰老是一种永久性的生长停滞状态，伴随着表型的深刻变化，可由多种外在或内在刺激触发。衰老是衰老机制通过拮抗多效性进化的过程水平的例子，并在肿瘤抑制中起主要作用，尽管越来越多的证据表明它参与了其他基本的生理过程。来自人类过早衰老疾病和转基因小鼠的证据（在转基因小鼠中可以特异性地删除衰老细胞）与衰老细胞在生命过程中的积累是导致晚年慢性疾病和损伤的模型一致。因此，去除衰老细胞或使其恢复到表型良性状态是转化医学的一个重要新兴目标。基于文本挖掘的现代生物信息学方法已经汇编了细胞衰老和年龄相关疾病的共同提及，从而可以对与此过程最密切相关的损伤进行公正的排名。根据这一模式，参与衰老在几个高度排名的病理证据进行审查，旁边的潜在方法消融衰老细胞或其逆转其主要表型与多酚或抑制剂的p38 MAP激酶。最后，潜在的衰老作为一个障碍，旨在治疗这些条件中的一些生物人工器官的发展进行了讨论。
Cellular senescence is a permanent state of growth arrest coupled with profound changes in phenotype that can be triggered by multiple extrinsic or intrinsic stimuli. Senescence is a process-level example of the evolution of ageing mechanisms through antagonistic pleiotropy and plays a primary role in tumour suppression, although evidence is mounting for its involvement in other fundamental physiological processes. Evidence from human premature ageing diseases and from transgenic mice in which it is possible to specifically delete senescent cells is consistent with a model in which the accumulation of senescent cells through the life course is responsible for later life chronic disease and impairment. The removal of senescent cells or their reversion to a phenotypically benign state is thus an important emerging goal of translational medicine.Modern bioinformatic approaches based on text mining have compiled co-mentions of cell senescence and age-related diseases allowing an impartial ranking of the impairments most closely associated with this process. Following this schema, the evidence for the involvement of senescence in several highly ranked pathologies is reviewed, alongside potential methods for the ablation of senescent cells or their reversion to their primary phenotype with polyphenolics or inhibitors of p38 MAP kinase. Lastly, the potential for senescence to act as a barrier to the development of bioartificial organs designed to treat some of these conditions is discussed.