Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue 英文参考文献.docVIP

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Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue 英文参考文献.doc

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Age-AssociatedChangesInOxidativeStressandNADMetabolismInHumanTissue英文参考文献

Age-AssociatedChangesInOxidativeStressandNAD+ MetabolismInHumanTissue HassinaMassudi1,2,RossGrant1,2*,NadyBraidy1,3,JadeGuest1,2,BruceFarnsworth2,GillesJ.Guillemin1,4 1Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia, 2Australasian ResearchInstitute,SydneyAdventistHospital,Sydney,NewSouthWales,Australia,3SchoolofPsychiatry,UniversityofNewSouthWales,FacultyofMedicine,Sydney, NewSouthWales,Australia,4StVincent’sCentreforAppliedMedicalResearch,Sydney,NewSouthWales,Australia Abstract Nicotinamide adenine dinucleotide (NAD+) is an essential electron transporter in mitochondrial respiration andoxidative phosphorylation.IngenomicDNA,NAD alsorepresentsthesolesubstrateforthenuclearrepairenzyme,poly(ADP-ribose) + polymerase (PARP) and the sirtuin family of NAD-dependent histone deacetylases. Age associated increases in oxidative nuclear damage have been associated with PARP-mediated NAD depletion and loss of SIRT1 activity in rodents. In this + study, we further investigated whether these same associations were present in aging human tissue. Humanpelvic skin samples were obtained from consenting patients aged between 15–77 and newborn babies (0–1 year old) (n=49) previously scheduled for an unrelated surgical procedure. DNA damage correlated strongly with age in both males (p=0.029; r=0.490) and females (p=0.003; r=0.600) whereas lipid oxidation (MDA) levels increased with age in males (p=0.004; r=0.623) but not females (p=0.3734; r=0.200). PARP activity significantly increased with age in males + (p,0.0001;r=0.768)andinverselycorrelatedwithtissueNAD levels(p=0.0003;r=20.639).Theseassociationswereless evident in females. A strong negative correlation was observed between NAD levels and age in both males (p=0.001; + r=20.706) and females (p=0.01; r=20.537). SIRT1 activity also negatively correlated with age in males (p=0.007; r=20.612) but not in females. Strong positive co