Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming.
Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming.
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通过一个短暂的重编程循环实现自然衰老组织的多组再生。
DOI：
10.1111/acel.13578
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发表时间：
2022-03
期刊：
影响因子：
7.8
通讯作者：
Serrano M
中科院分区：
文献类型：
--
作者：
Chondronasiou D;Gill D;Mosteiro L;Urdinguio RG;Berenguer-Llergo A;Aguilera M;Durand S;Aprahamian F;Nirmalathasan N;Abad M;Martin-Herranz DE;Stephan-Otto Attolini C;Prats N;Kroemer G;Fraga MF;Reik W;Serrano M
多能性因子OCT 4、SOX 2、KLF 4和MYC（OSKM）的表达可以在称为重编程的过程中将体细胞分化的细胞转化为多能干细胞。值得注意的是，部分和可逆的重编程不会改变细胞身份，但可以逆转细胞中的衰老标志物，提高老年小鼠修复组织损伤的能力，并延长早衰小鼠的寿命。然而，人们对所涉及的机制知之甚少。在这里，我们已经研究了DNA甲基化组，转录组和代谢组在自然老化的小鼠受到一个单一的瞬时OSKM表达的变化。我们发现，这足以逆转胰腺、肝脏、脾脏和血液中衰老时发生的DNA甲基化变化。同样，我们观察到转录变化的逆转，特别是关于已知在衰老过程中发生变化的生物过程。最后，一些随着衰老而改变的血清代谢物和生物标志物也在短暂重编程后恢复到年轻水平。这些观察结果表明，OSKM表达的单个时期可以驱动表观遗传学、转录组学和代谢组学变化，使多个组织和血清中的构型更年轻。在自然衰老小鼠中，瞬时OSKM激活的单周期能够部分逆转几种组织中的年龄相关变化。具体来说，我们可以在DNA甲基化、转录以及血清代谢组水平上捕获随着衰老发生的改变的逆转。这些变化在OSKM停止后长达四周的时间内保持稳定。
The expression of the pluripotency factors OCT4, SOX2, KLF4, and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, partial and reversible reprogramming does not change cell identity but can reverse markers of aging in cells, improve the capacity of aged mice to repair tissue injuries, and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome, and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen, and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites and biomarkers altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic, and metabolomic changes toward a younger configuration in multiple tissues and in the serum. A single cycle of transient OSKM activation in naturally aged mice is able to partially reverse age‐associated changes in several tissues. Specifically, we could capture reversion of alterations occurring with aging at the level of DNA methylation, transcription, as well as, serum metabolome. These changes were stable for a period of up to four weeks after OSKM cessation.
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影响因子：
64.8
作者：
Abad, Maria;Mosteiro, Lluc;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
6.5
作者：
Dumit, Veronica I.;Kuettner, Victoria;Kaeppler, Jakob;Piera-Velazquez, Sonsoles;Jimenez, Sergio A.;Bruckner-Tuderman, Leena;Uitto, Jouni;Dengjel, Joern
通讯作者：
Dengjel, Joern
影响因子：
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作者：
Brink, Thore C.;Demetrius, Lloyd;Lehrach, Hans;Adjaye, James
通讯作者：
Adjaye, James
影响因子：
56.9
作者：
Chen, Yanpu;Luttmann, Felipe F.;Braun, Thomas
通讯作者：
Braun, Thomas