Epigenetic and senescence markers indicate an accelerated ageing-like state in women with preeclamptic pregnancies

Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cell...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	EBioMedicine Jg. 70; S. 103536
Hauptverfasser:	Suvakov, Sonja, Ghamrawi, Ranine, Cubro, Hajrunisa, Tu, Haitao, White, Wendy M., Tobah, Yvonne S. Butler, Milic, Natasa M., Grande, Joseph P., Cunningham, Julie M., Chebib, Fouad T., Prata, Larissa G.P. Langhi, Zhu, Yi, Tchkonia, Tamara, Kirkland, James L., Nath, Karl A., Milosavljevic, Aleksandar, Garovic, Vesna D.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Netherlands Elsevier B.V 01.08.2021 Elsevier
Schlagworte:	Adipose Tissue - metabolism Adult Advanced Basic Science ageing Biomarkers - metabolism Cells, Cultured Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 - metabolism Dasatinib - pharmacology Epigenesis, Genetic epigenetic clock Female Humans Internal Medicine Kidney - metabolism Klotho Proteins - metabolism Mesenchymal Stem Cells - drug effects Mesenchymal Stem Cells - metabolism Pre-Eclampsia - genetics Pre-Eclampsia - metabolism Pre-Eclampsia - pathology preeclampsia Pregnancy Protein Kinase Inhibitors - pharmacology Research Paper senescence senescence ageing preeclampsia epigenetic clock
ISSN:	2352-3964, 2352-3964
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Abstract	Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology. We compared women with preeclampsia vs. normotensive pregnancies with respect to epigenetic markers of ageing and markers of senescence in tissues/organs affected by preeclampsia (blood, urine, adipose tissue, and kidney). We demonstrate that preeclamptic compared to normotensive pregnant women: (i) undergo accelerated epigenetic ageing during pregnancy, as demonstrated by an “epigenetic clock”; (ii) exhibit higher levels/expression of senescence-associated secretory phenotype factors in blood and adipose tissue; (iii) display increased expression of p16INK4A in adipose tissue and renal sections, and (iv) demonstrate decreased levels of urinary α-Klotho (an anti-ageing protein) at the time of delivery. Finally, we provide data indicating that pre-treatment with dasatinib, a senolytic agent, rescues the angiogenic potential of mesenchymal stem cells (MSC) obtained from preeclamptic pregnancies, and promotes angiogenesis, even under pro-inflammatory conditions. Taken together, our results identify senescence as one of the mechanisms underpinning the pathophysiology of preeclampsia. Therapeutic strategies that target senescent cells may offer novel mechanism-based treatments for preeclampsia. This work was supported by NIH grants, R01 HL136348, R37 AG013925, P01 AG062413, R01 DK11916, generous gifts from the Connor Fund, Robert J. and Theresa W. Ryan and from The George G. Beasley family, the Noaber Foundation, and the Henry and Emma Meyer Professorship in Molecular Genetics.
AbstractList	Background: Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology. Methods: We compared women with preeclampsia vs. normotensive pregnancies with respect to epigenetic markers of ageing and markers of senescence in tissues/organs affected by preeclampsia (blood, urine, adipose tissue, and kidney). Findings: We demonstrate that preeclamptic compared to normotensive pregnant women: (i) undergo accelerated epigenetic ageing during pregnancy, as demonstrated by an “epigenetic clock”; (ii) exhibit higher levels/expression of senescence-associated secretory phenotype factors in blood and adipose tissue; (iii) display increased expression of p16INK4A in adipose tissue and renal sections, and (iv) demonstrate decreased levels of urinary α-Klotho (an anti-ageing protein) at the time of delivery. Finally, we provide data indicating that pre-treatment with dasatinib, a senolytic agent, rescues the angiogenic potential of mesenchymal stem cells (MSC) obtained from preeclamptic pregnancies, and promotes angiogenesis, even under pro-inflammatory conditions. Interpretation: Taken together, our results identify senescence as one of the mechanisms underpinning the pathophysiology of preeclampsia. Therapeutic strategies that target senescent cells may offer novel mechanism-based treatments for preeclampsia. Funding: This work was supported by NIH grants, R01 HL136348, R37 AG013925, P01 AG062413, R01 DK11916, generous gifts from the Connor Fund, Robert J. and Theresa W. Ryan and from The George G. Beasley family, the Noaber Foundation, and the Henry and Emma Meyer Professorship in Molecular Genetics. Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology. We compared women with preeclampsia vs. normotensive pregnancies with respect to epigenetic markers of ageing and markers of senescence in tissues/organs affected by preeclampsia (blood, urine, adipose tissue, and kidney). We demonstrate that preeclamptic compared to normotensive pregnant women: (i) undergo accelerated epigenetic ageing during pregnancy, as demonstrated by an “epigenetic clock”; (ii) exhibit higher levels/expression of senescence-associated secretory phenotype factors in blood and adipose tissue; (iii) display increased expression of p16INK4A in adipose tissue and renal sections, and (iv) demonstrate decreased levels of urinary α-Klotho (an anti-ageing protein) at the time of delivery. Finally, we provide data indicating that pre-treatment with dasatinib, a senolytic agent, rescues the angiogenic potential of mesenchymal stem cells (MSC) obtained from preeclamptic pregnancies, and promotes angiogenesis, even under pro-inflammatory conditions. Taken together, our results identify senescence as one of the mechanisms underpinning the pathophysiology of preeclampsia. Therapeutic strategies that target senescent cells may offer novel mechanism-based treatments for preeclampsia. This work was supported by NIH grants, R01 HL136348, R37 AG013925, P01 AG062413, R01 DK11916, generous gifts from the Connor Fund, Robert J. and Theresa W. Ryan and from The George G. Beasley family, the Noaber Foundation, and the Henry and Emma Meyer Professorship in Molecular Genetics. AbstractBackgroundPreeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology. MethodsWe compared women with preeclampsia vs. normotensive pregnancies with respect to epigenetic markers of ageing and markers of senescence in tissues/organs affected by preeclampsia (blood, urine, adipose tissue, and kidney). FindingsWe demonstrate that preeclamptic compared to normotensive pregnant women: (i) undergo accelerated epigenetic ageing during pregnancy, as demonstrated by an “epigenetic clock”; (ii) exhibit higher levels/expression of senescence-associated secretory phenotype factors in blood and adipose tissue; (iii) display increased expression of p16 INK4A in adipose tissue and renal sections, and (iv) demonstrate decreased levels of urinary α-Klotho (an anti-ageing protein) at the time of delivery. Finally, we provide data indicating that pre-treatment with dasatinib, a senolytic agent, rescues the angiogenic potential of mesenchymal stem cells (MSC) obtained from preeclamptic pregnancies, and promotes angiogenesis, even under pro-inflammatory conditions. InterpretationTaken together, our results identify senescence as one of the mechanisms underpinning the pathophysiology of preeclampsia. Therapeutic strategies that target senescent cells may offer novel mechanism-based treatments for preeclampsia. FundingThis work was supported by NIH grants, R01 HL136348, R37 AG013925, P01 AG062413, R01 DK11916, generous gifts from the Connor Fund, Robert J. and Theresa W. Ryan and from The George G. Beasley family, the Noaber Foundation, and the Henry and Emma Meyer Professorship in Molecular Genetics. Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology.BACKGROUNDPreeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology.We compared women with preeclampsia vs. normotensive pregnancies with respect to epigenetic markers of ageing and markers of senescence in tissues/organs affected by preeclampsia (blood, urine, adipose tissue, and kidney).METHODSWe compared women with preeclampsia vs. normotensive pregnancies with respect to epigenetic markers of ageing and markers of senescence in tissues/organs affected by preeclampsia (blood, urine, adipose tissue, and kidney).We demonstrate that preeclamptic compared to normotensive pregnant women: (i) undergo accelerated epigenetic ageing during pregnancy, as demonstrated by an "epigenetic clock"; (ii) exhibit higher levels/expression of senescence-associated secretory phenotype factors in blood and adipose tissue; (iii) display increased expression of p16INK4A in adipose tissue and renal sections, and (iv) demonstrate decreased levels of urinary α-Klotho (an anti-ageing protein) at the time of delivery. Finally, we provide data indicating that pre-treatment with dasatinib, a senolytic agent, rescues the angiogenic potential of mesenchymal stem cells (MSC) obtained from preeclamptic pregnancies, and promotes angiogenesis, even under pro-inflammatory conditions.FINDINGSWe demonstrate that preeclamptic compared to normotensive pregnant women: (i) undergo accelerated epigenetic ageing during pregnancy, as demonstrated by an "epigenetic clock"; (ii) exhibit higher levels/expression of senescence-associated secretory phenotype factors in blood and adipose tissue; (iii) display increased expression of p16INK4A in adipose tissue and renal sections, and (iv) demonstrate decreased levels of urinary α-Klotho (an anti-ageing protein) at the time of delivery. Finally, we provide data indicating that pre-treatment with dasatinib, a senolytic agent, rescues the angiogenic potential of mesenchymal stem cells (MSC) obtained from preeclamptic pregnancies, and promotes angiogenesis, even under pro-inflammatory conditions.Taken together, our results identify senescence as one of the mechanisms underpinning the pathophysiology of preeclampsia. Therapeutic strategies that target senescent cells may offer novel mechanism-based treatments for preeclampsia.INTERPRETATIONTaken together, our results identify senescence as one of the mechanisms underpinning the pathophysiology of preeclampsia. Therapeutic strategies that target senescent cells may offer novel mechanism-based treatments for preeclampsia.This work was supported by NIH grants, R01 HL136348, R37 AG013925, P01 AG062413, R01 DK11916, generous gifts from the Connor Fund, Robert J. and Theresa W. Ryan and from The George G. Beasley family, the Noaber Foundation, and the Henry and Emma Meyer Professorship in Molecular Genetics.FUNDINGThis work was supported by NIH grants, R01 HL136348, R37 AG013925, P01 AG062413, R01 DK11916, generous gifts from the Connor Fund, Robert J. and Theresa W. Ryan and from The George G. Beasley family, the Noaber Foundation, and the Henry and Emma Meyer Professorship in Molecular Genetics. Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology. We compared women with preeclampsia vs. normotensive pregnancies with respect to epigenetic markers of ageing and markers of senescence in tissues/organs affected by preeclampsia (blood, urine, adipose tissue, and kidney). We demonstrate that preeclamptic compared to normotensive pregnant women: (i) undergo accelerated epigenetic ageing during pregnancy, as demonstrated by an "epigenetic clock"; (ii) exhibit higher levels/expression of senescence-associated secretory phenotype factors in blood and adipose tissue; (iii) display increased expression of p16 in adipose tissue and renal sections, and (iv) demonstrate decreased levels of urinary α-Klotho (an anti-ageing protein) at the time of delivery. Finally, we provide data indicating that pre-treatment with dasatinib, a senolytic agent, rescues the angiogenic potential of mesenchymal stem cells (MSC) obtained from preeclamptic pregnancies, and promotes angiogenesis, even under pro-inflammatory conditions. Taken together, our results identify senescence as one of the mechanisms underpinning the pathophysiology of preeclampsia. Therapeutic strategies that target senescent cells may offer novel mechanism-based treatments for preeclampsia. This work was supported by NIH grants, R01 HL136348, R37 AG013925, P01 AG062413, R01 DK11916, generous gifts from the Connor Fund, Robert J. and Theresa W. Ryan and from The George G. Beasley family, the Noaber Foundation, and the Henry and Emma Meyer Professorship in Molecular Genetics.
ArticleNumber	103536
Author	Suvakov, Sonja Tchkonia, Tamara Zhu, Yi Tu, Haitao Kirkland, James L. Nath, Karl A. Grande, Joseph P. White, Wendy M. Garovic, Vesna D. Ghamrawi, Ranine Cubro, Hajrunisa Prata, Larissa G.P. Langhi Milic, Natasa M. Tobah, Yvonne S. Butler Milosavljevic, Aleksandar Cunningham, Julie M. Chebib, Fouad T.
Author_xml	– sequence: 1 givenname: Sonja orcidid: 0000-0002-3743-1213 surname: Suvakov fullname: Suvakov, Sonja email: Suvakov.sonja@mayo.edu organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA – sequence: 2 givenname: Ranine surname: Ghamrawi fullname: Ghamrawi, Ranine email: ghamrawi.ranine@mayo.edu organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA – sequence: 3 givenname: Hajrunisa surname: Cubro fullname: Cubro, Hajrunisa email: hajrunisa.cubro@louisville.edu organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA – sequence: 4 givenname: Haitao surname: Tu fullname: Tu, Haitao organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA – sequence: 5 givenname: Wendy M. surname: White fullname: White, Wendy M. email: White.Wendy@mayo.edu organization: Department of Obstetrics and Gynaecology, Mayo Clinic, Rochester, MN, USA – sequence: 6 givenname: Yvonne S. Butler surname: Tobah fullname: Tobah, Yvonne S. Butler email: ButlerTobah.Yvonne@mayo.edu organization: Department of Obstetrics and Gynaecology, Mayo Clinic, Rochester, MN, USA – sequence: 7 givenname: Natasa M. surname: Milic fullname: Milic, Natasa M. organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA – sequence: 8 givenname: Joseph P. surname: Grande fullname: Grande, Joseph P. email: grande@mayo.edu organization: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA – sequence: 9 givenname: Julie M. surname: Cunningham fullname: Cunningham, Julie M. email: cunningham.julie@mayo.edu organization: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA – sequence: 10 givenname: Fouad T. orcidid: 0000-0002-3949-5720 surname: Chebib fullname: Chebib, Fouad T. email: Chebib.Fouad@mayo.edu organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA – sequence: 11 givenname: Larissa G.P. Langhi surname: Prata fullname: Prata, Larissa G.P. Langhi email: langhi.larissa@mayo.edu organization: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA – sequence: 12 givenname: Yi surname: Zhu fullname: Zhu, Yi email: Zhu.Yi@mayo.edu organization: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA – sequence: 13 givenname: Tamara surname: Tchkonia fullname: Tchkonia, Tamara email: Tchkonia.Tamar@mayo.edu organization: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA – sequence: 14 givenname: James L. surname: Kirkland fullname: Kirkland, James L. email: Kirkland.James@mayo.edu organization: Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA – sequence: 15 givenname: Karl A. surname: Nath fullname: Nath, Karl A. email: Nath.Karl@mayo.edu organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA – sequence: 16 givenname: Aleksandar surname: Milosavljevic fullname: Milosavljevic, Aleksandar email: amilosav@bcm.edu organization: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA – sequence: 17 givenname: Vesna D. orcidid: 0000-0001-6891-0578 surname: Garovic fullname: Garovic, Vesna D. email: garovic.vesna@mayo.edu organization: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/34391091$$D View this record in MEDLINE/PubMed
BookMark	eNqFUk1r3DAQNSWlSdP8gkLxsZfd6sOyLUoDJaRtIJBD2rPQSmNHu7K0lbwp-fcdx2lIAmUvkmb03htp5r0tDkIMUBTvKVlSQutP6yWsXByWjDCKGS54_ao4YlywBZd1dfDkfFic5LwmhFBRYbJ9UxzyiktKJD0q0vnW9RBgdKbUwZYZz9lAMFAOOm0g5dIF64weAe9LbQx4SBjZUvfgQr_wbgNlHieAC-WfOACubrwptwnAeD1sJ20M-qCDcZDfFa877TOcPOzHxa9v5z_Pfiwur75fnH29XJias3FB65ZQycjKstawrjGNrZqOA3Btpewaam0nbQ1tB2B527QV14KaFXDODGksPy4uZl0b9Vptk8MP3amonbpPxNQrnfBtHhSztWaWrQhpRdXIpiVcE8EE8JYbQQVqnc5a291qAIsNGpP2z0Sf3wR3o_p4q1peCy4oCnx8EEjx9w7yqAaHffZeB4i7rJioaSVJJWuEfnha67HIv6EhgM8Ak2LOCbpHCCVqcodaq3t3qMkdanYHsuQLlnE4NRenBzu_h_tl5gLO69ZBUhkniSaxLoEZsaFuD__0Bd94F9BVfgN3kNdxlwJaQVGVmSLqevLuZF1GCeFMNijw-f8Ce8v_BewxAFg
CitedBy_id	crossref_primary_10_1161_CIRCRESAHA_121_319895 crossref_primary_10_1126_scitranslmed_adi0077 crossref_primary_10_1161_HYPERTENSIONAHA_123_22250 crossref_primary_10_1007_s11886_022_01830_1 crossref_primary_10_3390_cells12091296 crossref_primary_10_1007_s00424_023_02810_2 crossref_primary_10_1038_s41591_022_01923_y crossref_primary_10_1016_j_placenta_2022_03_005 crossref_primary_10_1155_2022_7202837 crossref_primary_10_1007_s00441_023_03768_4 crossref_primary_10_3390_genes14122132 crossref_primary_10_3390_ijms26030902 crossref_primary_10_34067_KID_0000000000000395 crossref_primary_10_3390_cells14130955 crossref_primary_10_3389_fmolb_2025_1520101 crossref_primary_10_1016_j_ebiom_2022_103912 crossref_primary_10_2147_JIR_S538337 crossref_primary_10_1016_j_arr_2023_101879 crossref_primary_10_1002_j_2040_4603_2023_tb00249_x crossref_primary_10_1210_endrev_bnae010 crossref_primary_10_1002_j_2040_4603_2023_tb00282_x crossref_primary_10_1111_aji_13904 crossref_primary_10_3389_fdmed_2022_822397 crossref_primary_10_3390_ijms232012698 crossref_primary_10_34067_KID_0000000605 crossref_primary_10_1016_j_repbio_2023_100734 crossref_primary_10_3389_fmed_2022_923334
Cites_doi	10.1038/s41440-019-0387-3 10.1093/ndt/gfl711 10.1161/HYPERTENSIONAHA.113.01115 10.1016/j.semnephrol.2018.10.005 10.1016/j.ebiom.2017.04.013 10.1016/j.ajog.2013.08.019 10.1038/s41591-018-0092-9 10.1038/nature13193 10.1016/j.jacc.2020.03.028 10.1186/s13293-019-0263-5 10.1186/1755-8794-4-84 10.1186/gb-2013-14-10-r115 10.3109/10641955.2016.1162315 10.1016/j.arr.2016.09.001 10.1161/HYPERTENSIONAHA.111.00250 10.1016/j.placenta.2013.12.010 10.1056/NEJMoa1704559 10.1081/PRG-120021060 10.1172/JCI17189 10.4161/epi.20388 10.3390/ijms21228810 10.1007/s00418-016-1435-6 10.3109/10641955.2013.796970 10.1161/CIRCULATIONAHA.118.037777
ContentType	Journal Article
Copyright	2021 The Author(s) The Author(s) Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved. 2021 The Author(s) 2021
Copyright_xml	– notice: 2021 The Author(s) – notice: The Author(s) – notice: Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved. – notice: 2021 The Author(s) 2021
DBID	6I. AAFTH AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM DOA
DOI	10.1016/j.ebiom.2021.103536
DatabaseName	ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic
DatabaseTitleList	MEDLINE - Academic MEDLINE
Database_xml	– sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Biology
EISSN	2352-3964
EndPage	103536
ExternalDocumentID	oai_doaj_org_article_2d6a2d2b00854797803a0525e383c515 PMC8365351 34391091 10_1016_j_ebiom_2021_103536 S2352396421003297 1_s2_0_S2352396421003297
Genre	Journal Article
GrantInformation	This work was supported by NIH grants, R01 HL136348, R37 AG013925, P01 AG062413, R01 DK11916, generous gifts from the Connor Fund, Robert J. and Theresa W. Ryan and from The George G. Beasley family, the Noaber Foundation, and the Henry and Emma Meyer Professorship in Molecular Genetics.
GrantInformation_xml	– fundername: NIA NIH HHS grantid: R37 AG013925 – fundername: NIDDK NIH HHS grantid: R01 DK119167 – fundername: NIA NIH HHS grantid: R01 AG013925 – fundername: NIA NIH HHS grantid: P01 AG062413 – fundername: NHLBI NIH HHS grantid: R01 HL136348
GroupedDBID	.1- .FO 0R~ 4.4 457 53G 5VS AAEDT AAEDW AAIKJ AALRI AAMRU AAXUO AAYWO ABMAC ACGFS ACVFH ADBBV ADCNI ADEZE ADRAZ ADVLN AEUPX AEXQZ AFPUW AFRHN AFTJW AGHFR AIGII AITUG AJUYK AKBMS AKRWK AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ AOIJS APXCP BCNDV EBS EJD FDB GROUPED_DOAJ HYE HZ~ IPNFZ KQ8 M41 M48 O9- OK1 RIG ROL RPM SSZ Z5R 0SF 6I. AACTN AAFTH AFCTW NCXOZ AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM
ID	FETCH-LOGICAL-c632t-16801920bd28c2f7c7d47f3ee3ad99f71ddf9d6e8feed387843a51cbe332c07d3
IEDL.DBID	DOA
ISICitedReferencesCount	31
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000689249500002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	2352-3964
IngestDate	Fri Oct 03 12:39:18 EDT 2025 Tue Nov 04 02:00:50 EST 2025 Wed Oct 01 14:12:46 EDT 2025 Thu Jan 02 22:56:47 EST 2025 Wed Nov 12 18:33:03 EST 2025 Tue Nov 18 20:38:57 EST 2025 Tue Jul 25 20:58:58 EDT 2023 Sun Feb 23 10:19:36 EST 2025 Tue Aug 26 17:01:34 EDT 2025
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Keywords	senescence ageing preeclampsia epigenetic clock
Language	English
License	This is an open access article under the CC BY-NC-ND license. Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c632t-16801920bd28c2f7c7d47f3ee3ad99f71ddf9d6e8feed387843a51cbe332c07d3
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ORCID	0000-0001-6891-0578 0000-0002-3743-1213 0000-0002-3949-5720
OpenAccessLink	https://doaj.org/article/2d6a2d2b00854797803a0525e383c515
PMID	34391091
PQID	2561490496
PQPubID	23479
PageCount	1
ParticipantIDs	doaj_primary_oai_doaj_org_article_2d6a2d2b00854797803a0525e383c515 pubmedcentral_primary_oai_pubmedcentral_nih_gov_8365351 proquest_miscellaneous_2561490496 pubmed_primary_34391091 crossref_primary_10_1016_j_ebiom_2021_103536 crossref_citationtrail_10_1016_j_ebiom_2021_103536 elsevier_sciencedirect_doi_10_1016_j_ebiom_2021_103536 elsevier_clinicalkeyesjournals_1_s2_0_S2352396421003297 elsevier_clinicalkey_doi_10_1016_j_ebiom_2021_103536
PublicationCentury	2000
PublicationDate	2021-08-01
PublicationDateYYYYMMDD	2021-08-01
PublicationDate_xml	– month: 08 year: 2021 text: 2021-08-01 day: 01
PublicationDecade	2020
PublicationPlace	Netherlands
PublicationPlace_xml	– name: Netherlands
PublicationTitle	EBioMedicine
PublicationTitleAlternate	EBioMedicine
PublicationYear	2021
Publisher	Elsevier B.V Elsevier
Publisher_xml	– name: Elsevier B.V – name: Elsevier
References	Christov, Neyra, Gupta, Leaf (bib0017) 2019; 39 Mace, Olgaard, Lewin (bib0018) 2020; 21 Rolnik, Wright, Poon (bib0002) 2017; 377 van Deursen (bib0005) 2014; 509 Garovic, White, Vaughan (bib0025) 2020; 75 Maynard, Min, Merchan (bib0003) 2003; 111 Xu, Pirtskhalava, Farr (bib0022) 2018; 24 James, Srinivasan, Alexander, Chamley (bib0023) 2014; 35 von Dadelszen, Magee, Roberts (bib0009) 2003; 22 Sun, Chai, Wu (bib0012) 2011; 4 Cohen (bib0013) 1988 White, Brost, Sun (bib0019) 2012; 7 Craici, Wagner, Bailey (bib0010) 2013; 61 Greer, Lyall, Perera, Boswell, Macara (bib0007) 1994; 84 Horvath (bib0015) 2013; 14 Kirkland, Tchkonia (bib0008) 2017; 21 White, Brost, Sun (bib0020) 2013; 32 White, Sun, Borowski (bib0021) 2016; 35 Staff, Benton, von Dadelszen (bib0027) 2013; 61 Weissgerber, Winham, Heinzen (bib0014) 2019; 140 Londero, Orsaria, Marzinotto (bib0006) 2016; 146 (bib0001) 2013; 122 Suvakov, Cubro, White (bib0004) 2019; 10 Garovic, Wagner, Petrovic (bib0011) 2007; 22 Huang, Hu, Han (bib0024) 2020; 43 Lisonkova, Joseph (bib0026) 2013; 209 Mencke, Hillebrands (bib0016) 2017; 35 von Dadelszen (10.1016/j.ebiom.2021.103536_bib0009) 2003; 22 Rolnik (10.1016/j.ebiom.2021.103536_bib0002) 2017; 377 White (10.1016/j.ebiom.2021.103536_bib0020) 2013; 32 Horvath (10.1016/j.ebiom.2021.103536_bib0015) 2013; 14 Staff (10.1016/j.ebiom.2021.103536_bib0027) 2013; 61 Mace (10.1016/j.ebiom.2021.103536_bib0018) 2020; 21 James (10.1016/j.ebiom.2021.103536_bib0023) 2014; 35 Greer (10.1016/j.ebiom.2021.103536_bib0007) 1994; 84 (10.1016/j.ebiom.2021.103536_bib0001) 2013; 122 Garovic (10.1016/j.ebiom.2021.103536_bib0011) 2007; 22 Xu (10.1016/j.ebiom.2021.103536_bib0022) 2018; 24 Mencke (10.1016/j.ebiom.2021.103536_bib0016) 2017; 35 Craici (10.1016/j.ebiom.2021.103536_bib0010) 2013; 61 Weissgerber (10.1016/j.ebiom.2021.103536_bib0014) 2019; 140 Lisonkova (10.1016/j.ebiom.2021.103536_bib0026) 2013; 209 Sun (10.1016/j.ebiom.2021.103536_bib0012) 2011; 4 Christov (10.1016/j.ebiom.2021.103536_bib0017) 2019; 39 Londero (10.1016/j.ebiom.2021.103536_bib0006) 2016; 146 Huang (10.1016/j.ebiom.2021.103536_bib0024) 2020; 43 Maynard (10.1016/j.ebiom.2021.103536_bib0003) 2003; 111 Suvakov (10.1016/j.ebiom.2021.103536_bib0004) 2019; 10 van Deursen (10.1016/j.ebiom.2021.103536_bib0005) 2014; 509 Cohen (10.1016/j.ebiom.2021.103536_bib0013) 1988 White (10.1016/j.ebiom.2021.103536_bib0019) 2012; 7 White (10.1016/j.ebiom.2021.103536_bib0021) 2016; 35 Kirkland (10.1016/j.ebiom.2021.103536_bib0008) 2017; 21 Garovic (10.1016/j.ebiom.2021.103536_bib0025) 2020; 75
References_xml	– volume: 21 start-page: 21 year: 2017 end-page: 28 ident: bib0008 article-title: Cellular senescence: a translational perspective publication-title: EBioMedicine – volume: 24 start-page: 1246 year: 2018 end-page: 1256 ident: bib0022 article-title: Senolytics improve physical function and increase lifespan in old age publication-title: Nat Med – volume: 39 start-page: 57 year: 2019 end-page: 75 ident: bib0017 article-title: Fibroblast growth factor 23 and Klotho in AKI publication-title: Semin Nephrol – volume: 509 start-page: 439 year: 2014 end-page: 446 ident: bib0005 article-title: The role of senescent cells in ageing publication-title: Nature – volume: 84 start-page: 937 year: 1994 end-page: 940 ident: bib0007 article-title: Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction? publication-title: Obstet Gynecol – volume: 4 start-page: 84 year: 2011 ident: bib0012 article-title: Batch effect correction for genome-wide methylation data with illumina infinium platform publication-title: BMC Med Genom – volume: 21 year: 2020 ident: bib0018 article-title: New aspects of the kidney in the regulation of fibroblast growth factor 23 (FGF23) and mineral homeostasis publication-title: Int J Mol Sci – volume: 377 start-page: 613 year: 2017 end-page: 622 ident: bib0002 article-title: Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia publication-title: N Engl J Med – volume: 35 start-page: 124 year: 2017 end-page: 146 ident: bib0016 article-title: The role of the anti-ageing protein Klotho in vascular physiology and pathophysiology publication-title: Ageing Res Rev – volume: 122 start-page: 1122 year: 2013 end-page: 1131 ident: bib0001 article-title: Report of the American college of obstetricians and gynecologists' task force on hypertension in pregnancy publication-title: Obstet Gynecol – year: 1988 ident: bib0013 article-title: Statistical power analysis for behavioral sciences – volume: 75 start-page: 2323 year: 2020 end-page: 2334 ident: bib0025 article-title: Incidence and long-term outcomes of hypertensive disorders of pregnancy publication-title: J Am Coll Cardiol – volume: 32 start-page: 257 year: 2013 end-page: 269 ident: bib0020 article-title: Genome-wide methylation profiling demonstrates hypermethylation in maternal leukocyte DNA in preeclamptic compared to normotensive pregnancies publication-title: Hypertens Pregnancy – volume: 22 start-page: 1136 year: 2007 end-page: 1143 ident: bib0011 article-title: Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia publication-title: Nephrol Dial Transplant – volume: 10 start-page: 49 year: 2019 ident: bib0004 article-title: Targeting senescence improves angiogenic potential of adipose-derived mesenchymal stem cells in patients with preeclampsia publication-title: Biol Sex Differ – volume: 22 start-page: 143 year: 2003 end-page: 148 ident: bib0009 article-title: Subclassification of preeclampsia publication-title: Hypertens Pregnancy – volume: 35 start-page: 77 year: 2014 end-page: 84 ident: bib0023 article-title: Can we fix it? Evaluating the potential of placental stem cells for the treatment of pregnancy disorders publication-title: Placenta – volume: 61 start-page: 1289 year: 2013 end-page: 1296 ident: bib0010 article-title: Podocyturia predates proteinuria and clinical features of preeclampsia: longitudinal prospective study publication-title: Hypertension – volume: 43 start-page: 263 year: 2020 end-page: 270 ident: bib0024 article-title: Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model publication-title: Hypertens Res – volume: 111 start-page: 649 year: 2003 end-page: 658 ident: bib0003 article-title: Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia publication-title: J Clin Invest – volume: 140 start-page: 1506 year: 2019 end-page: 1518 ident: bib0014 article-title: Reveal, don't conceal: transforming data visualization to improve transparency publication-title: Circulation – volume: 146 start-page: 191 year: 2016 end-page: 204 ident: bib0006 article-title: Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study publication-title: Histochem Cell Biol – volume: 14 start-page: R115 year: 2013 ident: bib0015 article-title: DNA methylation age of human tissues and cell types publication-title: Genome Biol – volume: 35 start-page: 394 year: 2016 end-page: 404 ident: bib0021 article-title: Preeclampsia/Eclampsia candidate genes show altered methylation in maternal leukocytes of preeclamptic women at the time of delivery publication-title: Hypertens Pregnancy – volume: 7 start-page: 729 year: 2012 end-page: 734 ident: bib0019 article-title: Normal early pregnancy: a transient state of epigenetic change favoring hypomethylation publication-title: Epigenetics – volume: 61 start-page: 932 year: 2013 end-page: 942 ident: bib0027 article-title: Redefining preeclampsia using placenta-derived biomarkers publication-title: Hypertension – volume: 209 start-page: 544.e1 year: 2013 end-page: 544.e12 ident: bib0026 article-title: Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease publication-title: Am J Obstet Gynecol – volume: 43 start-page: 263 year: 2020 ident: 10.1016/j.ebiom.2021.103536_bib0024 article-title: Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model publication-title: Hypertens Res doi: 10.1038/s41440-019-0387-3 – volume: 22 start-page: 1136 year: 2007 ident: 10.1016/j.ebiom.2021.103536_bib0011 article-title: Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia publication-title: Nephrol Dial Transplant doi: 10.1093/ndt/gfl711 – volume: 61 start-page: 1289 year: 2013 ident: 10.1016/j.ebiom.2021.103536_bib0010 article-title: Podocyturia predates proteinuria and clinical features of preeclampsia: longitudinal prospective study publication-title: Hypertension doi: 10.1161/HYPERTENSIONAHA.113.01115 – volume: 39 start-page: 57 year: 2019 ident: 10.1016/j.ebiom.2021.103536_bib0017 article-title: Fibroblast growth factor 23 and Klotho in AKI publication-title: Semin Nephrol doi: 10.1016/j.semnephrol.2018.10.005 – volume: 21 start-page: 21 year: 2017 ident: 10.1016/j.ebiom.2021.103536_bib0008 article-title: Cellular senescence: a translational perspective publication-title: EBioMedicine doi: 10.1016/j.ebiom.2017.04.013 – volume: 84 start-page: 937 year: 1994 ident: 10.1016/j.ebiom.2021.103536_bib0007 article-title: Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction? publication-title: Obstet Gynecol – volume: 209 start-page: 544.e1 issue: 6 year: 2013 ident: 10.1016/j.ebiom.2021.103536_bib0026 article-title: Incidence of preeclampsia: risk factors and outcomes associated with early- versus late-onset disease publication-title: Am J Obstet Gynecol doi: 10.1016/j.ajog.2013.08.019 – year: 1988 ident: 10.1016/j.ebiom.2021.103536_bib0013 – volume: 24 start-page: 1246 year: 2018 ident: 10.1016/j.ebiom.2021.103536_bib0022 article-title: Senolytics improve physical function and increase lifespan in old age publication-title: Nat Med doi: 10.1038/s41591-018-0092-9 – volume: 509 start-page: 439 year: 2014 ident: 10.1016/j.ebiom.2021.103536_bib0005 article-title: The role of senescent cells in ageing publication-title: Nature doi: 10.1038/nature13193 – volume: 75 start-page: 2323 year: 2020 ident: 10.1016/j.ebiom.2021.103536_bib0025 article-title: Incidence and long-term outcomes of hypertensive disorders of pregnancy publication-title: J Am Coll Cardiol doi: 10.1016/j.jacc.2020.03.028 – volume: 10 start-page: 49 year: 2019 ident: 10.1016/j.ebiom.2021.103536_bib0004 article-title: Targeting senescence improves angiogenic potential of adipose-derived mesenchymal stem cells in patients with preeclampsia publication-title: Biol Sex Differ doi: 10.1186/s13293-019-0263-5 – volume: 4 start-page: 84 year: 2011 ident: 10.1016/j.ebiom.2021.103536_bib0012 article-title: Batch effect correction for genome-wide methylation data with illumina infinium platform publication-title: BMC Med Genom doi: 10.1186/1755-8794-4-84 – volume: 14 start-page: R115 year: 2013 ident: 10.1016/j.ebiom.2021.103536_bib0015 article-title: DNA methylation age of human tissues and cell types publication-title: Genome Biol doi: 10.1186/gb-2013-14-10-r115 – volume: 35 start-page: 394 year: 2016 ident: 10.1016/j.ebiom.2021.103536_bib0021 article-title: Preeclampsia/Eclampsia candidate genes show altered methylation in maternal leukocytes of preeclamptic women at the time of delivery publication-title: Hypertens Pregnancy doi: 10.3109/10641955.2016.1162315 – volume: 35 start-page: 124 year: 2017 ident: 10.1016/j.ebiom.2021.103536_bib0016 article-title: The role of the anti-ageing protein Klotho in vascular physiology and pathophysiology publication-title: Ageing Res Rev doi: 10.1016/j.arr.2016.09.001 – volume: 61 start-page: 932 year: 2013 ident: 10.1016/j.ebiom.2021.103536_bib0027 article-title: Redefining preeclampsia using placenta-derived biomarkers publication-title: Hypertension doi: 10.1161/HYPERTENSIONAHA.111.00250 – volume: 35 start-page: 77 year: 2014 ident: 10.1016/j.ebiom.2021.103536_bib0023 article-title: Can we fix it? Evaluating the potential of placental stem cells for the treatment of pregnancy disorders publication-title: Placenta doi: 10.1016/j.placenta.2013.12.010 – volume: 377 start-page: 613 issue: 7 year: 2017 ident: 10.1016/j.ebiom.2021.103536_bib0002 article-title: Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia publication-title: N Engl J Med doi: 10.1056/NEJMoa1704559 – volume: 22 start-page: 143 year: 2003 ident: 10.1016/j.ebiom.2021.103536_bib0009 article-title: Subclassification of preeclampsia publication-title: Hypertens Pregnancy doi: 10.1081/PRG-120021060 – volume: 111 start-page: 649 year: 2003 ident: 10.1016/j.ebiom.2021.103536_bib0003 article-title: Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia publication-title: J Clin Invest doi: 10.1172/JCI17189 – volume: 7 start-page: 729 year: 2012 ident: 10.1016/j.ebiom.2021.103536_bib0019 article-title: Normal early pregnancy: a transient state of epigenetic change favoring hypomethylation publication-title: Epigenetics doi: 10.4161/epi.20388 – volume: 122 start-page: 1122 year: 2013 ident: 10.1016/j.ebiom.2021.103536_bib0001 article-title: Report of the American college of obstetricians and gynecologists' task force on hypertension in pregnancy publication-title: Obstet Gynecol – volume: 21 year: 2020 ident: 10.1016/j.ebiom.2021.103536_bib0018 article-title: New aspects of the kidney in the regulation of fibroblast growth factor 23 (FGF23) and mineral homeostasis publication-title: Int J Mol Sci doi: 10.3390/ijms21228810 – volume: 146 start-page: 191 year: 2016 ident: 10.1016/j.ebiom.2021.103536_bib0006 article-title: Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study publication-title: Histochem Cell Biol doi: 10.1007/s00418-016-1435-6 – volume: 32 start-page: 257 year: 2013 ident: 10.1016/j.ebiom.2021.103536_bib0020 article-title: Genome-wide methylation profiling demonstrates hypermethylation in maternal leukocyte DNA in preeclamptic compared to normotensive pregnancies publication-title: Hypertens Pregnancy doi: 10.3109/10641955.2013.796970 – volume: 140 start-page: 1506 year: 2019 ident: 10.1016/j.ebiom.2021.103536_bib0014 article-title: Reveal, don't conceal: transforming data visualization to improve transparency publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.118.037777
SSID	ssj0001542358
Score	2.3650932
Snippet	Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be... AbstractBackgroundPreeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific... Background: Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy...
SourceID	doaj pubmedcentral proquest pubmed crossref elsevier
SourceType	Open Website Open Access Repository Aggregation Database Index Database Enrichment Source Publisher
StartPage	103536
SubjectTerms	Adipose Tissue - metabolism Adult Advanced Basic Science ageing Biomarkers - metabolism Cells, Cultured Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 - metabolism Dasatinib - pharmacology Epigenesis, Genetic epigenetic clock Female Humans Internal Medicine Kidney - metabolism Klotho Proteins - metabolism Mesenchymal Stem Cells - drug effects Mesenchymal Stem Cells - metabolism Pre-Eclampsia - genetics Pre-Eclampsia - metabolism Pre-Eclampsia - pathology preeclampsia Pregnancy Protein Kinase Inhibitors - pharmacology Research Paper senescence
Title	Epigenetic and senescence markers indicate an accelerated ageing-like state in women with preeclamptic pregnancies
URI	https://www.clinicalkey.com/#!/content/1-s2.0-S2352396421003297 https://www.clinicalkey.es/playcontent/1-s2.0-S2352396421003297 https://dx.doi.org/10.1016/j.ebiom.2021.103536 https://www.ncbi.nlm.nih.gov/pubmed/34391091 https://www.proquest.com/docview/2561490496 https://pubmed.ncbi.nlm.nih.gov/PMC8365351 https://doaj.org/article/2d6a2d2b00854797803a0525e383c515
Volume	70
WOSCitedRecordID	wos000689249500002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 2352-3964 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0001542358 issn: 2352-3964 databaseCode: DOA dateStart: 20140101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lj9MwELZgBRIXxJvyWBmJIxHxI7ZzBLQrTiskQOrN8itQ2M1WSReJf8-MnZQW0O6FYxs7aWYmM980M98Q8lK2olMBkJtXqamk87IyIfGKRSUkDyK2zuRhE_rkxCyX7YedUV9YE1bogYvgXvOoHI_cIzaQGvlyhMPZawlSq9Dk9nIOqGcnmSr9wRJ7QPNkuYZXolVyphzKxV0Jm9shO-QMu86bTND8Oyxl9v696PQ3-vyziHInKh3fIbcnOEnflNu4S66l_h65WQZM_rxPhqM1sm1ioyJ1faQjeraADzM9w7qcYaT4zhqrouA4dSFAFELyiEjBz0BUq05X3xPNXUewkma-Bor_3dL1kFIAc1rjueHDlzLnd3xAPh8ffXr3vpqmLFRBCb6pmDII82ofuQm800FHqTuRknCxbTvNYuzaqJLpIJwKo40UrmHBJyF4qHUUD8lBf96nx4QCGPLJq044FqWvma8FB22B13DOqOAXhM9CtmGiIMdJGKd2rjX7ZrNmLGrGFs0syKvtpnVh4Lh8-VvU3nYp0mfnL8Co7GRU9iqjWhA5697OHargU-FEq8uvrf-1LY2TXxgtsyO3tf2IVolGCQk3yKjVC6K2OyfoUyDN1Zd8MZumBceAb3tcn84vRsuR47WFBBDWPCqmuhWKwH5rQIrwg_eMeE9q-0f61ddMPm6EakTDnvwPMT8lt_BWSj3lM3KwGS7Sc3Ij_NisxuGQXNdLc5if619AS06X
linkProvider	Directory of Open Access Journals
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Epigenetic+and+senescence+markers+indicate+an+accelerated+ageing-like+state+in+women+with+preeclamptic+pregnancies&rft.jtitle=EBioMedicine&rft.au=Sonja+Suvakov&rft.au=Ranine+Ghamrawi&rft.au=Hajrunisa+Cubro&rft.au=Haitao+Tu&rft.date=2021-08-01&rft.pub=Elsevier&rft.issn=2352-3964&rft.eissn=2352-3964&rft.volume=70&rft.spage=103536&rft_id=info:doi/10.1016%2Fj.ebiom.2021.103536&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_2d6a2d2b00854797803a0525e383c515
thumbnail_m	http://cvtisr.summon.serialssolutions.com/2.0.0/image/custom?url=https%3A%2F%2Fcdn.clinicalkey.com%2Fck-thumbnails%2F23523964%2FS2352396421X00084%2Fcov150h.gif