Cardiac aging in mice and humans: the role of mitochondrial oxidative stress.
Age is a major risk factor for cardiovascular diseases, not only because it prolongs exposure to several other cardiovascular risks, but also owing to intrinsic cardiac aging, which reduces cardiac functional reserve, predisposes the heart to stress, and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, including left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenuated in mice overexpressing catalase targeted to mitochondria. These findings demonstrate the critical role of mitochondrial reactive oxygen species in cardiac aging and support the potential application of mitochondrial antioxidants to cardiac aging and age-related cardiovascular diseases.
Dai
Dao-Fu
DF
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Rabinovitch
Peter S
PS
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004703:Endocrine System / Q000502:physiology; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000503:physiopathology* / Q000628:therapy; D051379:Mice; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000502:physiology
D000975:Antioxidants; D017382:Reactive Oxygen Species; D011941:Receptors, Adrenergic
J Gerontol. 1956 Jul;11(3):298-300
13332224
Circ J. 2006 Apr;70(4):482-8
16565569
Nat Med. 2007 Aug;13(8):970-4
17660827
Circ Res. 2004 Feb 20;94(3):377-84
14670841
Cardiovasc Res. 2008 Jul 15;79(2):208-17
18430751
Am Heart J. 1996 Mar;131(3):620-2
8604653
Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1351-8
17557916
Am J Physiol Heart Circ Physiol. 2001 Aug;281(2):H581-9
11454560
Nature. 2004 May 27;429(6990):417-23
15164064
Circulation. 1999 Jan 5-12;99(1):127-34
9884389
Science. 2005 Jun 24;308(5730):1909-11
15879174
Cardiovasc Res. 2006 May 1;70(2):191-9
16497286
Cardiovasc Res. 2001 Jan;49(1):56-68
11121796
Am J Physiol. 1998 Dec;275(6):H2087-94
9843808
Circulation. 2007 Oct 16;116(16):1776-83
17893275
J Am Soc Echocardiogr. 1997 Mar;10(2):169-78
9083973
Exp Gerontol. 2003 Jan-Feb;38(1-2):35-46
12543259
J Am Soc Echocardiogr. 2004 Mar;17(3):290-7
14981433
Lancet. 2004 Nov 13-19;364(9447):1786-8
15541452
Cardiovasc Res. 1998 Feb;37(2):405-23
9614496
Nat Med. 2004 Nov;10(11):1200-7
15489859
J Gerontol A Biol Sci Med Sci. 2008 Aug;63(8):813-22
18772469
Toxicol Sci. 1999 Dec;52(2 Suppl):41-8
10630589
Cardiovasc Res. 2005 May 1;66(2):233-44
15820192
Circulation. 2003 Jan 21;107(2):346-54
12538439
Nat Rev Mol Cell Biol. 2006 Aug;7(8):589-600
16936699
Science. 2009 Apr 3;324(5923):98-102
19342590
Circulation. 2009 Jun 2;119(21):2789-97
19451351
Nature. 2003 Jan 9;421(6919):182-7
12483226
Hypertension. 1998 Feb;31(2):643-8
9461235
Nat Genet. 2008 Apr;40(4):392-4
18311139
J Gerontol A Biol Sci Med Sci. 2006 Jan;61(1):28-35
16456192
J Gerontol A Biol Sci Med Sci. 2001 Aug;56(8):B340-9
11487592
Exp Gerontol. 1996 May-Jun;31(3):387-92
9415121
J Mol Cell Cardiol. 2002 Mar;34(3):297-308
11945022
Science. 2004 Sep 3;305(5689):1423-6
15353793
JAMA. 1991 Oct 2;266(13):1812-6
1890710
Circ Res. 2008 Nov 7;103(10):1058-71
18988903
Hypertension. 2005 Aug;46(2):426-32
15998712
J Clin Invest. 2009 Mar;119(3):524-30
19197138
Nat Genet. 2004 Dec;36(12):1275-81
15565107
J Mol Cell Cardiol. 2002 Jun;34(6):641-8
12054851
Microsc Res Tech. 2002 Nov 15;59(4):335-8
12424798
Ann Intern Med. 2003 Oct 21;139(8):642-8
14568852
Am J Physiol. 1994 Nov;267(5 Pt 2):H1795-803
7977810
Cell. 2007 Jul 27;130(2):247-58
17662940
JAMA. 2006 Nov 8;296(18):2209-16
17090767
Science. 2005 Jul 15;309(5733):481-4
16020738
Cell. 2005 Feb 25;120(4):483-95
15734681
Rejuvenation Res. 2008 Aug;11(4):725-33
18729805
Genes Dev. 2009 Aug 1;23(15):1714-36
19651984
Biochem Biophys Res Commun. 1997 Jan 23;230(3):630-5
9015375
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9986-90
12904575
Heart Fail Rev. 2002 Jan;7(1):63-9
11790923
Circulation. 2007 Feb 6;115(5):e69-171
17194875
Am J Physiol Cell Physiol. 2007 Feb;292(2):C670-86
17020935
Cell. 2003 Sep 19;114(6):763-76
14505575
Circulation. 2003 Jan 28;107(3):490-7
12551876
Cardiovasc Res. 2004 Nov 1;64(2):198-207
15485678
Aging Cell. 2005 Apr;4(2):57-64
15771609