In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice
In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice
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DOI：
10.1038/s43587-022-00183-2
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发表时间：
2022-03-01
期刊：
影响因子：
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通讯作者：
Belmonte, Juan Carlos Izpisua
中科院分区：
文献类型：
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作者：
Browder, Kristen C.;Reddy, Pradeep;Belmonte, Juan Carlos Izpisua
通过短时间表达重编程因子（Oct4、Sox 2、Klf 4和c-Myc）的部分重编程使衰老细胞恢复年轻的表观遗传特征，并延长过早衰老小鼠模型的寿命。然而，在生理老化的野生型小鼠中长期部分重编程的影响是未知的。在这里，我们进行了各种长期的部分重编程方案，包括不同的发病时间，在生理老化。长期的部分重编程导致不同组织（如肾脏和皮肤）以及生物体水平的再生效果;治疗的持续时间决定了有益效果的程度。再生效应与表观遗传时钟的逆转以及代谢和转录组学变化有关，包括参与炎症、衰老和应激反应途径的基因表达减少。总的来说，我们的观察表明，部分重编程协议可以被设计为安全和有效地防止年龄相关的生理变化。我们进一步得出结论，较长期的部分重编程方案在延缓衰老表型方面比短期重编程更有效。
Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the life span of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown. Here, we performed various long-term partial reprogramming regimens, including different onset timings, during physiological aging. Long-term partial reprogramming lead to rejuvenating effects in different tissues, such as the kidney and skin, and at the organismal level; duration of the treatment determined the extent of the beneficial effects. The rejuvenating effects were associated with a reversion of the epigenetic clock and metabolic and transcriptomic changes, including reduced expression of genes involved in the inflammation, senescence and stress response pathways. Overall, our observations indicate that partial reprogramming protocols can be designed to be safe and effective in preventing age-related physiological changes. We further conclude that longer-term partial reprogramming regimens are more effective in delaying aging phenotypes than short-term reprogramming.