当前位置: X-MOL 学术Exp. Cell Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The aging proteostasis decline: From nematode to human
Experimental Cell Research ( IF 3.3 ) Pub Date : 2021-01-09 , DOI: 10.1016/j.yexcr.2021.112474
Anatoly Meller , Reut Shalgi

The aging proteostasis decline manifests in a failure of aging cells and organisms to properly respond to proteotoxic challenges. This proteostasis collapse has long been considered a hallmark of aging in nematodes, and has recently been shown to occur also in human cells upon entry to senescence, opening the way to exploring the phenomenon in the broader context of human aging. Cellular senescence is part of the normal human physiology of aging, with senescent cell accumulation as a prominent feature of aged tissues. Being highly resistant to cell death, senescent cells, as they accumulate, become pro-inflammatory and promote disease. Here we discuss the causes of human senescence proteostasis decline, in view of the current literature on nematodes, on the one hand, and senescence, on the other hand. We review two major aspects of the phenomenon: (1) the decline in transcriptional activation of stress-response pathways, and (2) impairments in proteasome function. We further outline potential underlying mechanisms of transcriptional proteostasis decline, focusing on reduced chromatin dynamics and compromised nuclear integrity. Finally, we discuss potential strategies for reinforcing proteostasis as a means to improve organismal health and address the relationship to senolytics.



中文翻译:

老化的蛋白稳态下降:从线虫到人类

老化的蛋白质稳态减少表现为老化的细胞和生物体无法正确应对蛋白质毒性挑战。长期以来,这种蛋白稳态塌陷一直被认为是线虫衰老的标志,最近已证明,进入衰老后人体细胞中也会发生这种变化,这为在更广泛的人类衰老环境中探索该现象开辟了道路。细胞衰老是人体正常衰老的一部分,衰老细胞的积累是衰老组织的突出特征。衰老细胞对细胞死亡具有高度抵抗力,随着它们的积累,它们会促炎并促进疾病。在这里,我们一方面根据目前关于线虫和另一方面针对衰老的文献来讨论人类衰老性蛋白稳态下降的原因。我们回顾了该现象的两个主要方面:(1)应激反应途径的转录激活下降,(2)蛋白酶体功能受损。我们进一步概述了转录蛋白稳态下降的潜在潜在机制,重点是减少染色质动力学和受损的核完整性。最后,我们讨论了增强蛋白稳态作为改善机体健康并解决与senolytics关系的一种手段的潜在策略。

更新日期:2021-01-20
down
wechat
bug