title: Aging and injury: alterations in cellular energetics and organ function.
abstract: Aging is characterized by increased oxidative stress, heightened inflammatory response, accelerated cellular senescence and progressive organ dysfunction. The homeostatic imbalance with aging significantly alters cellular responses to injury. Though it is unclear whether cellular energetic imbalance is a cause or effect of the aging process, preservation of mitochondrial function has been reported to be important in organ function restoration following severe injury. Unintentional injuries are ranked among the top 10 causes of death in adults of both sexes, 65 years and older. Aging associated decline in mitochondrial function has been shown to enhance the vulnerability of heart, lung, liver and kidney to ischemia/reperfusion injury. Studies have identified alterations in the level or activity of factors such as SIRT1, PGC-1α, HIF-1α and c-MYC involved in key regulatory processes in the maintenance of mitochondrial structural integrity, biogenesis and function. Studies using experimental models of hemorrhagic injury and burn have demonstrated significant influence of aging in metabolic regulation and organ function. Understanding the age-associated molecular mechanisms regulating mitochondrial dysfunction following injury is important towards identifying novel targets and therapeutic strategies to improve the outcome after injury in the elderly.
authors.affiliation: Department of Medical Laboratory, Imaging and Radiological Sciences, Georgia Regents University, Augusta, GA30912, USA.
authors.forename: Ninu
authors.initials: N
authors.lastname: Poulose
authors.affiliation: Department of Medical Laboratory, Imaging and Radiological Sciences, Georgia Regents University, Augusta, GA30912, USA ; Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA30912, USA.
authors.forename: Raghavan
authors.initials: R
authors.lastname: Raju
keywords: aging; hemorrhage; hypoxia; ischemia; mitochondria; sirt1
references.citation: Emerg Med Clin North Am. 1998 Feb;16(1):257-74
references.pmid: 9496324
references.citation: Biogerontology. 2013 Oct;14(5):531-41
references.pmid: 24026668
references.citation: Curr Opin Microbiol. 2012 Oct;15(5):596-602
references.pmid: 22981392
references.citation: Kidney Int. 2012 Oct;82(7):735-6
references.pmid: 22975995
references.citation: Diabetes. 2011 Jan;60(1):157-67
references.pmid: 20929977
references.citation: Hypertension. 2005 Aug;46(2):426-32
references.pmid: 15998712
references.citation: J Mol Cell Cardiol. 1997 Nov;29(11):3081-9
references.pmid: 9405182
references.citation: Cell. 2013 Dec 19;155(7):1624-38
references.pmid: 24360282
references.citation: Shock. 2009 Jan;31(1):11-20
references.pmid: 18636047
references.citation: Science. 2005 Jun 24;308(5730):1909-11
references.pmid: 15879174
references.citation: Trends Endocrinol Metab. 2009 Nov;20(9):429-35
references.pmid: 19800814
references.citation: PLoS One. 2013 Sep 10;8(9):e74050
references.pmid: 24040162
references.citation: Mol Med. 2012 Mar 27;18:209-14
references.pmid: 22113495
references.citation: Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):510-4
references.pmid: 9435222
references.citation: Shock. 2008 Jun;29(6):670-4
references.pmid: 17998889
references.citation: J Am Geriatr Soc. 1972 Apr;20(4):145-7
references.pmid: 5016631
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6689-93
references.pmid: 10359773
references.citation: Arch Biochem Biophys. 2001 Jan 1;385(1):117-28
references.pmid: 11361007
references.citation: Aging Dis. 2011 Apr 19;2(2):174-180
references.pmid: 21532982
references.citation: J Neurotrauma. 2008 Feb;25(2):153-71
references.pmid: 18260798
references.citation: J Am Geriatr Soc. 2006 Oct;54(10):1590-5
references.pmid: 17038079
references.citation: Biogerontology. 2010 Feb;11(1):17-30
references.pmid: 19350411
references.citation: Pflugers Arch. 2013 May;465(5):669-85
references.pmid: 23525672
references.citation: Science. 2008 Sep 26;321(5897):1807-12
references.pmid: 18772396
references.citation: Front Aging Neurosci. 2013 Dec 18;5:95
references.pmid: 24385964
references.citation: Biochim Biophys Acta. 2011 Nov;1812(11):1446-51
references.pmid: 21554952
references.citation: Neurobiol Aging. 2014 Jun;35(6):1345-51
references.pmid: 24360504
references.citation: Shock. 2005 Nov;24(5):421-7
references.pmid: 16247327
references.citation: Eur Heart J. 1990 May;11 Suppl C:22-9
references.pmid: 2188839
references.citation: Am J Physiol. 1996 Nov;271(5 Pt 2):H2145-53
references.pmid: 8945935
references.citation: PLoS One. 2012;7(12):e51457
references.pmid: 23251540
references.citation: Trends Cardiovasc Med. 2011 Jan;21(1):27-32
references.pmid: 22498017
references.citation: Gastroenterology. 2011 Dec;141(6):2188-2199.e6
references.pmid: 21854730
references.citation: Mol Cell Biol. 2005 Jul;25(14):6225-34
references.pmid: 15988031
references.citation: Mol Med. 2011 May-Jun;17(5-6):542-9
references.pmid: 21193900
references.citation: Aging Dis. 2012 Apr;3(2):171-80
references.pmid: 22724078
references.citation: J Immunol. 2014 Jan 15;192(2):612-22
references.pmid: 24337739
references.citation: J Neurotrauma. 2005 Jan;22(1):95-105
references.pmid: 15665605
references.citation: Crit Care Med. 2009 Jun;37(6):1978-87
references.pmid: 19384226
references.citation: Am J Physiol Heart Circ Physiol. 2013 Jun 15;304(12):H1727-32
references.pmid: 23604707
references.citation: J Clin Invest. 2010 May;120(5):1494-505
references.pmid: 20364083
references.citation: J Neurosci. 2013 Dec 11;33(50):19480-91
references.pmid: 24336714
references.citation: Science. 2000 Sep 1;289(5484):1567-9
references.pmid: 10968795
references.citation: J Clin Invest. 2013 Mar;123(3):951-7
references.pmid: 23454757
references.citation: Aging Cell. 2009 Feb;8(1):73-5
references.pmid: 19077044
references.citation: Cell Rep. 2014 Mar 13;6(5):836-43
references.pmid: 24582957
references.citation: Stroke. 2004 Nov;35(11):2571-5
references.pmid: 15472083
references.citation: Acad Emerg Med. 1996 Nov;3(11):1041-5
references.pmid: 8922013
references.citation: Endocrinology. 2009 Jan;150(1):24-32
references.pmid: 18801909
references.citation: Cardiovasc Res. 1999 Mar;41(3):594-602
references.pmid: 10435031
references.citation: Comp Biochem Physiol Biochem Mol Biol. 1994 Aug;108(4):501-12
references.pmid: 7953069
references.citation: Biochim Biophys Acta. 2010 Aug;1804(8):1666-75
references.pmid: 19879981
references.citation: Vaccine. 2000 Feb 25;18(16):1717-20
references.pmid: 10689155
references.citation: Sports Med. 2005;35(5):413-27
references.pmid: 15896090
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1141-9
references.pmid: 17185630
references.citation: Can J Physiol Pharmacol. 2013 Aug;91(8):593-600
references.pmid: 23889593
references.citation: J Invest Dermatol. 2001 Nov;117(5):1027-35
references.pmid: 11710909
references.citation: J Cell Biol. 2009 Apr 20;185(2):203-11
references.pmid: 19364925
references.citation: Crit Care. 2011;15(2):R92
references.pmid: 21392371
references.citation: J Hepatol. 2010 Nov;53(5):950-61
references.pmid: 20739078
references.citation: J Lab Clin Med. 1994 Dec;124(6):843-51
references.pmid: 7798799
references.citation: Ann N Y Acad Sci. 1998 Nov 20;854:224-38
references.pmid: 9928433
references.citation: Transplant Proc. 2005 May;37(4):1653-6
references.pmid: 15919422
references.citation: Cancer Cell. 2007 May;11(5):407-20
references.pmid: 17482131
references.citation: Am J Cardiol. 1998 Aug 1;82(3):345-51
references.pmid: 9708665
references.citation: Curr Aging Sci. 2008 Mar;1(1):10-21
references.pmid: 20021368
references.citation: Autophagy. 2012 Jan;8(1):140-1
references.pmid: 22170150
references.citation: Am J Physiol Cell Physiol. 2007 Jun;292(6):C1983-92
references.pmid: 17344313
references.citation: Radiol Clin North Am. 2008 Jul;46(4):643-52, v
references.pmid: 18922285
references.citation: Circ Res. 1991 Jun;68(6):1560-8
references.pmid: 2036710
references.citation: Mol Cell. 2010 Jun 25;38(6):864-78
references.pmid: 20620956
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G268-74
references.pmid: 16959950
references.citation: J Am Soc Nephrol. 2011 Jan;22(1):28-38
references.pmid: 21209252
references.citation: Acta Neurochir Suppl. 2005;95:425-7
references.pmid: 16463895
references.citation: Age (Dordr). 2011 Sep;33(3):321-36
references.pmid: 20878490
references.citation: J Surg Res. 2008 Jun 15;147(2):229-36
references.pmid: 18498875
references.citation: Aging Cell. 2006 Dec;5(6):463-71
references.pmid: 17054663