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
ABSTRACT 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, cycles of brief OSKM expression do not change cell identity but can reverse markers of aging in cells 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 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 towards a younger configuration in multiple tissues and in the serum.
Reik Wolf、Chondronasiou Dafni、Mosteiro Lluc、Aprahamian Fanny、Nirmalathasan Nitharsshini、Fraga Mario F.、Aguilera Monica、Otto-Attolini Camille Stephan、Kroemer Guido、Durand Sylvere、Berenguer Antonio、Martin-Herranz Daniel E.、Serrano Manuel、Prats Neus、Urdinguio Rocio G.、Gill Diljeet、Abad Maria
Epigenetics Programme, Babraham Institute||Centre for Trophoblast Research, University of Cambridge||Wellcome Trust Sanger InstituteInstitute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST)GenentechMetabolomics and Cell Biology Platforms, Institut Gustave Roussy||Centre de Recherche des Cordeliers, Equipe labellis¨|e par la Ligue contre le cancer, Universit¨| de Paris, Sorbonne Universit¨|||Inserm U1138, Institut Universitaire de FranceMetabolomics and Cell Biology Platforms, Institut Gustave Roussy||Centre de Recherche des Cordeliers, Equipe labellis¨|e par la Ligue contre le cancer, Universit¨| de Paris, Sorbonne Universit¨|||Inserm U1138, Institut Universitaire de FranceCancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center (CINN CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA) and Department of Organisms and Systems Biology (BOS), University of Oviedo, and CIBER of Rare Diseases (CIBERER)Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST)Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST)Metabolomics and Cell Biology Platforms, Institut Gustave Roussy||Centre de Recherche des Cordeliers, Equipe labellis¨|e par la Ligue contre le cancer, Universit¨| de Paris, Sorbonne Universit¨|||Inserm U1138, Institut Universitaire de France||P?le de Biologie, H?pital Europ¨|en Georges Pompidou||Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences||Karolinska Institute, Department of Women?ˉs and Children?ˉs Health, Karolinska University HospitalMetabolomics and Cell Biology Platforms, Institut Gustave Roussy||Centre de Recherche des Cordeliers, Equipe labellis¨|e par la Ligue contre le cancer, Universit¨| de Paris, Sorbonne Universit¨|||Inserm U1138, Institut Universitaire de FranceInstitute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST)Chronomics LtdInstitute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST)||Catalan Institution for Research and Advanced Studies (ICREA)Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST)Cancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center (CINN CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA) and Department of Organisms and Systems Biology (BOS), University of Oviedo, and CIBER of Rare Diseases (CIBERER)Epigenetics Programme, Babraham InstituteVall d?ˉHebron Institute of Oncology (VHIO)
分子生物学细胞生物学遗传学
Reik Wolf,Chondronasiou Dafni,Mosteiro Lluc,Aprahamian Fanny,Nirmalathasan Nitharsshini,Fraga Mario F.,Aguilera Monica,Otto-Attolini Camille Stephan,Kroemer Guido,Durand Sylvere,Berenguer Antonio,Martin-Herranz Daniel E.,Serrano Manuel,Prats Neus,Urdinguio Rocio G.,Gill Diljeet,Abad Maria.Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/2022.01.20.477063.点此复制
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