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Article: Adult mesenchymal stem cell ageing interplays with depressed mitochondrial Ndufs6

TitleAdult mesenchymal stem cell ageing interplays with depressed mitochondrial Ndufs6
Authors
Issue Date2020
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html
Citation
Cell Death & Disease, 2020, v. 11, p. article no. 1075 How to Cite?
AbstractMesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy to treat many degenerative diseases. Accumulating evidence shows that the function of MSCs declines with age, thus limiting their regenerative capacity. Nonetheless, the underlying mechanisms that control MSC ageing are not well understood. We show that compared with bone marrow-MSCs (BM-MSCs) isolated from young and aged samples, NADH dehydrogenase (ubiquinone) iron-sulfur protein 6 (Ndufs6) is depressed in aged MSCs. Similar to that of Ndufs6 knockout (Ndufs6(-/-)) mice, MSCs exhibited a reduced self-renewal and differentiation capacity with a tendency to senescence in the presence of an increased p53/p21 level. Downregulation of Ndufs6 by siRNA also accelerated progression of wild-type BM-MSCs to an aged state. In contrast, replenishment of Ndufs6 in Ndufs6(-/-)-BM-MSCs significantly rejuvenated senescent cells and restored their proliferative ability. Compared with BM-MSCs, Ndufs6(-/-)-BM-MSCs displayed increased intracellular and mitochondrial reactive oxygen species (ROS), and decreased mitochondrial membrane potential. Treatment of Ndufs6(-/-)-BM-MSCs with mitochondrial ROS inhibitor Mito-TEMPO notably reversed the cellular senescence and reduced the increased p53/p21 level. We provide direct evidence that impairment of mitochondrial Ndufs6 is a putative accelerator of adult stem cell ageing that is associated with excessive ROS accumulation and upregulation of p53/p21. It also indicates that manipulation of mitochondrial function is critical and can effectively protect adult stem cells against senescence.
Persistent Identifierhttp://hdl.handle.net/10722/296353
ISSN
2023 Impact Factor: 8.1
2023 SCImago Journal Rankings: 2.447
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Y-
dc.contributor.authorGuo, L-
dc.contributor.authorHan, S-
dc.contributor.authorChen, L-
dc.contributor.authorLi, C-
dc.contributor.authorZhang, Z-
dc.contributor.authorHong, Y-
dc.contributor.authorZhang, X-
dc.contributor.authorZhou, X-
dc.contributor.authorJiang, D-
dc.contributor.authorLiang, X-
dc.contributor.authorQiu, J-
dc.contributor.authorZhang, J-
dc.contributor.authorLi, X-
dc.contributor.authorZhong, S-
dc.contributor.authorLiao, C-
dc.contributor.authorYan, B-
dc.contributor.authorTse, HF-
dc.contributor.authorLian, Q-
dc.date.accessioned2021-02-22T04:54:06Z-
dc.date.available2021-02-22T04:54:06Z-
dc.date.issued2020-
dc.identifier.citationCell Death & Disease, 2020, v. 11, p. article no. 1075-
dc.identifier.issn2041-4889-
dc.identifier.urihttp://hdl.handle.net/10722/296353-
dc.description.abstractMesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy to treat many degenerative diseases. Accumulating evidence shows that the function of MSCs declines with age, thus limiting their regenerative capacity. Nonetheless, the underlying mechanisms that control MSC ageing are not well understood. We show that compared with bone marrow-MSCs (BM-MSCs) isolated from young and aged samples, NADH dehydrogenase (ubiquinone) iron-sulfur protein 6 (Ndufs6) is depressed in aged MSCs. Similar to that of Ndufs6 knockout (Ndufs6(-/-)) mice, MSCs exhibited a reduced self-renewal and differentiation capacity with a tendency to senescence in the presence of an increased p53/p21 level. Downregulation of Ndufs6 by siRNA also accelerated progression of wild-type BM-MSCs to an aged state. In contrast, replenishment of Ndufs6 in Ndufs6(-/-)-BM-MSCs significantly rejuvenated senescent cells and restored their proliferative ability. Compared with BM-MSCs, Ndufs6(-/-)-BM-MSCs displayed increased intracellular and mitochondrial reactive oxygen species (ROS), and decreased mitochondrial membrane potential. Treatment of Ndufs6(-/-)-BM-MSCs with mitochondrial ROS inhibitor Mito-TEMPO notably reversed the cellular senescence and reduced the increased p53/p21 level. We provide direct evidence that impairment of mitochondrial Ndufs6 is a putative accelerator of adult stem cell ageing that is associated with excessive ROS accumulation and upregulation of p53/p21. It also indicates that manipulation of mitochondrial function is critical and can effectively protect adult stem cells against senescence.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddis/index.html-
dc.relation.ispartofCell Death & Disease-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleAdult mesenchymal stem cell ageing interplays with depressed mitochondrial Ndufs6-
dc.typeArticle-
dc.identifier.emailZhang, Z: zhucex1a@hku.hk-
dc.identifier.emailYan, B: yanbin14@hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hk-
dc.identifier.authorityYan, B=rp01940-
dc.identifier.authorityTse, HF=rp00428-
dc.identifier.authorityLian, Q=rp00267-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41419-020-03289-w-
dc.identifier.pmid33323934-
dc.identifier.pmcidPMC7738680-
dc.identifier.scopuseid_2-s2.0-85097523686-
dc.identifier.hkuros321288-
dc.identifier.volume11-
dc.identifier.spagearticle no. 1075-
dc.identifier.epagearticle no. 1075-
dc.identifier.isiWOS:000600140800003-
dc.publisher.placeUnited Kingdom-

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