长寿
生物
衰老
基因组不稳定性
DNA损伤
Gadd45型
DNA修复
细胞生物学
蛋白质稳态
自噬
遗传学
细胞周期
细胞
细胞周期检查点
基因
细胞凋亡
DNA
作者
Alexey Moskalev,Zeljka Smit-McBride,Mikhail Shaposhnikov,Ekaterina Plyusnina,Alex Zhavoronkov,Arie Budovsky,Robi Tăcutu,Vadim E. Fraifeld
标识
DOI:10.1016/j.arr.2011.09.003
摘要
The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis – all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions.
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