دورية أكاديمية
أعرض في EDS

Restoring mitochondrial DNA copy number preserves mitochondrial function and delays vascular aging in mice.

التفاصيل البيبلوغرافية
العنوان: Restoring mitochondrial DNA copy number preserves mitochondrial function and delays vascular aging in mice.
المؤلفون: Foote K; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK., Reinhold J; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK., Yu EPK; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK., Figg NL; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK., Finigan A; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK., Murphy MP; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Bennett MR; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
المصدر: Aging cell [Aging Cell] 2018 Aug; Vol. 17 (4), pp. e12773. Date of Electronic Publication: 2018 May 09.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Pub., c2002-
مواضيع طبية MeSH: Aging/*genetics , DNA Copy Number Variations/*genetics , DNA, Mitochondrial/*genetics , Mitochondria/*genetics , Vascular Stiffness/*genetics, Animals ; DNA, Mitochondrial/metabolism ; Female ; Male ; Mice ; Mitochondria/metabolism
مستخلص: Aging is the largest risk factor for cardiovascular disease, yet the molecular mechanisms underlying vascular aging remain unclear. Mitochondrial DNA (mtDNA) damage is linked to aging, but whether mtDNA damage or mitochondrial dysfunction is present and directly promotes vascular aging is unknown. Furthermore, mechanistic studies in mice are severely hampered by long study times and lack of sensitive, repeatable and reproducible parameters of arterial aging at standardized early time points. We examined the time course of multiple invasive and noninvasive arterial physiological parameters and structural changes of arterial aging in mice, how aging affects vessel mitochondrial function, and the effects of gain or loss of mitochondrial function on vascular aging. Vascular aging was first detected by 44 weeks (wk) of age, with reduced carotid compliance and distensibility, increased β-stiffness index and increased aortic pulse wave velocity (PWV). Aortic collagen content and elastin breaks also increased at 44 wk. Arterial mtDNA copy number (mtCN) and the mtCN-regulatory proteins TFAM, PGC1α and Twinkle were reduced by 44 wk, associated with reduced mitochondrial respiration. Overexpression of the mitochondrial helicase Twinkle (Tw + ) increased mtCN and improved mitochondrial respiration in arteries, and delayed physiological and structural aging in all parameters studied. Conversely, mice with defective mitochondrial polymerase-gamma (PolG) and reduced mtDNA integrity demonstrated accelerated vascular aging. Our study identifies multiple early and reproducible parameters for assessing vascular aging in mice. Arterial mitochondrial respiration reduces markedly with age, and reduced mtDNA integrity and mitochondrial function directly promote vascular aging.
(© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
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معلومات مُعتمدة: PG/13/25/30014 International British Heart Foundation (BHF); MC_UU_00015/3 United Kingdom MRC_ Medical Research Council; PG/13/25/30014 United Kingdom BHF_ British Heart Foundation; PG/16/63/32307 International British Heart Foundation (BHF); MC_U105663142 International Medical Research Council UK; PG/16/11/32021 United Kingdom BHF_ British Heart Foundation; MC_U105663142 United Kingdom MRC_ Medical Research Council; FS/10/70/28507 United Kingdom BHF_ British Heart Foundation; RG/13/14/30314 International British Heart Foundation (BHF); 110158/Z/15/Z United Kingdom WT_ Wellcome Trust; International BHF Centre for Research Excellence; PG/14/69/31032 United Kingdom BHF_ British Heart Foundation; PG/11/57/29003 United Kingdom BHF_ British Heart Foundation; International National Institute for Health Research Cambridge Biomedical Research Centre; PG/16/63/32307 United Kingdom BHF_ British Heart Foundation; RG/13/14/30314 United Kingdom BHF_ British Heart Foundation; PG/14/69/31032 International British Heart Foundation (BHF); International The Academy of Medical Sciences; 110159/Z/15/Z International Wellcome Trust PhD Fellowship
فهرسة مساهمة: Keywords: aging; mitochondria; mitochondrial DNA; vascular stiffness
المشرفين على المادة: 0 (DNA, Mitochondrial)
تواريخ الأحداث: Date Created: 20180511 Date Completed: 20191014 Latest Revision: 20230209
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6052475
DOI: 10.1111/acel.12773
PMID: 29745022
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-9726
DOI:10.1111/acel.12773