Age-associated changes in oxidative stress and NAD+ metabolism in human tissue

Nicotinamide adenine dinucleotide (NAD(+)) is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD(+) also represents the sole substrate for the nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP) and the sirtuin family of NAD-depend...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2012-07, Vol.7 (7), p.e42357-e42357
Main Authors: Massudi, Hassina, Grant, Ross, Braidy, Nady, Guest, Jade, Farnsworth, Bruce, Guillemin, Gilles J
Format: Article
Language:English
Subjects:
Adenine
Adenosine diphosphate
Adolescent
Adult
Age
Aged
Aging
Aging - genetics
Aging - metabolism
Alzheimer's disease
Alzheimers disease
Apoptosis
Babies
Biology
Biomarkers - metabolism
Cancer
Catabolism
Correlation
Damage accumulation
Deoxyribonucleic acid
Depletion
DNA
DNA Damage
DNA repair
Electron transport
Enzymes
Female
Females
Hospitals
Humans
Infant, Newborn
Lipid Peroxidation
Lipids
Male
Males
Medicine
Metabolism
Middle Aged
Mitochondria
NAD
NAD - metabolism
Nicotinamide
Nicotinamide adenine dinucleotide
Oxidation
Oxidative metabolism
Oxidative phosphorylation
Oxidative Stress
Peroxidation
Pharmacology
Phosphorylation
Physiology
Poly(ADP-ribose)
Poly(ADP-ribose) polymerase
Poly(ADP-ribose) Polymerases - metabolism
Polymerase
Proteins
Repair
Ribose
Rodents
Sex Characteristics
Signaling
SIRT1 protein
Sirtuin 1 - metabolism
Skin
Surgery
Transporter
Young Adult
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c592t-15edd6f599b227961f6e1723c53dc5eb17f8cb033ebcbdba3efc4a62f0891e4a3
cites
container_end_page e42357
container_issue 7
container_start_page e42357
container_title PloS one
container_volume 7
creator Massudi, Hassina
Grant, Ross
Braidy, Nady
Guest, Jade
Farnsworth, Bruce
Guillemin, Gilles J
description Nicotinamide adenine dinucleotide (NAD(+)) is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD(+) also represents the sole substrate for the nuclear repair enzyme, 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. Human pelvic 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
doi_str_mv 10.1371/journal.pone.0042357
format article
fullrecord <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1325527653</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_595d60ab48ee4604b97b3889815f5503</doaj_id><sourcerecordid>2941554901</sourcerecordid><originalsourceid>FETCH-LOGICAL-c592t-15edd6f599b227961f6e1723c53dc5eb17f8cb033ebcbdba3efc4a62f0891e4a3</originalsourceid><addsrcrecordid>eNptkltv1DAQhSMEoqXwDxBE4gUJZfElduIXpFXLpVJVXuDZGtuTXa8Se7GTCv59s2xatQj5wZb9nTMz1imK15SsKG_ox12cUoB-tY8BV4TUjIvmSXFKFWeVZIQ_fXA-KV7kvCNE8FbK58UJY23dNpKcFtfrDVaQc7QeRnSl3ULYYC59KONv72D0N1jmMWHOJQRXXq8vPpQDjmBi7_Nw4LbTAKEcfc4TviyeddBnfLXsZ8XPL59_nH-rrr5_vTxfX1VWKDZWVKBzshNKGcYaJWknkTaMW8GdFWho07XWEM7RWOMMcOxsDZJ1pFUUa-Bnxduj776PWS9fkTXlTAjWSMFn4vJIuAg7vU9-gPRHR_D670VMGw1p9LZHLZRwkoCpW8RaktqoxvC2VS0VnRDk4PVpqTaZAZ3FMCboH5k-fgl-qzfxRvOaNJSp2eD9YpDirwnzqAefLfY9BIzT3DfhRMyL0hl99w_6_-nqI2VTzDlhd98MJfoQjzuVPsRDL_GYZW8eDnIvussDvwVIKLgy</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1325527653</pqid></control><display><type>article</type><title>Age-associated changes in oxidative stress and NAD+ metabolism in human tissue</title><source>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</source><source>PubMed Central</source><creator>Massudi, Hassina ; Grant, Ross ; Braidy, Nady ; Guest, Jade ; Farnsworth, Bruce ; Guillemin, Gilles J</creator><contributor>Polymenis, Michael</contributor><creatorcontrib>Massudi, Hassina ; Grant, Ross ; Braidy, Nady ; Guest, Jade ; Farnsworth, Bruce ; Guillemin, Gilles J ; Polymenis, Michael</creatorcontrib><description>Nicotinamide adenine dinucleotide (NAD(+)) is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD(+) also represents the sole substrate for the nuclear repair enzyme, 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. Human pelvic 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&lt;0.0001; r = 0.768) and inversely correlated with tissue NAD(+) levels (p = 0.0003; r = -0.639). These associations were less evident in females. A strong negative correlation was observed between NAD(+) levels and age in both males (p = 0.001; r = -0.706) and females (p = 0.01; r = -0.537). SIRT1 activity also negatively correlated with age in males (p = 0.007; r = -0.612) but not in females. Strong positive correlations were also observed between lipid peroxidation and DNA damage (p&lt;0.0001; r = 0.4962), and PARP activity and NAD(+) levels (p = 0.0213; r = 0.5241) in post pubescent males. This study provides quantitative evidence in support of the hypothesis that hyperactivation of PARP due to an accumulation of oxidative damage to DNA during aging may be responsible for increased NAD(+) catabolism in human tissue. The resulting NAD(+) depletion may play a major role in the aging process, by limiting energy production, DNA repair and genomic signalling.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0042357</identifier><identifier>PMID: 22848760</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenine ; Adenosine diphosphate ; Adolescent ; Adult ; Age ; Aged ; Aging ; Aging - genetics ; Aging - metabolism ; Alzheimer's disease ; Alzheimers disease ; Apoptosis ; Babies ; Biology ; Biomarkers - metabolism ; Cancer ; Catabolism ; Correlation ; Damage accumulation ; Deoxyribonucleic acid ; Depletion ; DNA ; DNA Damage ; DNA repair ; Electron transport ; Enzymes ; Female ; Females ; Hospitals ; Humans ; Infant, Newborn ; Lipid Peroxidation ; Lipids ; Male ; Males ; Medicine ; Metabolism ; Middle Aged ; Mitochondria ; NAD ; NAD - metabolism ; Nicotinamide ; Nicotinamide adenine dinucleotide ; Oxidation ; Oxidative metabolism ; Oxidative phosphorylation ; Oxidative Stress ; Peroxidation ; Pharmacology ; Phosphorylation ; Physiology ; Poly(ADP-ribose) ; Poly(ADP-ribose) polymerase ; Poly(ADP-ribose) Polymerases - metabolism ; Polymerase ; Proteins ; Repair ; Ribose ; Rodents ; Sex Characteristics ; Signaling ; SIRT1 protein ; Sirtuin 1 - metabolism ; Skin ; Surgery ; Transporter ; Young Adult</subject><ispartof>PloS one, 2012-07, Vol.7 (7), p.e42357-e42357</ispartof><rights>Massudi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Massudi et al 2012 Massudi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-15edd6f599b227961f6e1723c53dc5eb17f8cb033ebcbdba3efc4a62f0891e4a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1325527653/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1325527653?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22848760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Polymenis, Michael</contributor><creatorcontrib>Massudi, Hassina</creatorcontrib><creatorcontrib>Grant, Ross</creatorcontrib><creatorcontrib>Braidy, Nady</creatorcontrib><creatorcontrib>Guest, Jade</creatorcontrib><creatorcontrib>Farnsworth, Bruce</creatorcontrib><creatorcontrib>Guillemin, Gilles J</creatorcontrib><title>Age-associated changes in oxidative stress and NAD+ metabolism in human tissue</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Nicotinamide adenine dinucleotide (NAD(+)) is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD(+) also represents the sole substrate for the nuclear repair enzyme, 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. Human pelvic 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&lt;0.0001; r = 0.768) and inversely correlated with tissue NAD(+) levels (p = 0.0003; r = -0.639). These associations were less evident in females. A strong negative correlation was observed between NAD(+) levels and age in both males (p = 0.001; r = -0.706) and females (p = 0.01; r = -0.537). SIRT1 activity also negatively correlated with age in males (p = 0.007; r = -0.612) but not in females. Strong positive correlations were also observed between lipid peroxidation and DNA damage (p&lt;0.0001; r = 0.4962), and PARP activity and NAD(+) levels (p = 0.0213; r = 0.5241) in post pubescent males. This study provides quantitative evidence in support of the hypothesis that hyperactivation of PARP due to an accumulation of oxidative damage to DNA during aging may be responsible for increased NAD(+) catabolism in human tissue. The resulting NAD(+) depletion may play a major role in the aging process, by limiting energy production, DNA repair and genomic signalling.</description><subject>Adenine</subject><subject>Adenosine diphosphate</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Aging</subject><subject>Aging - genetics</subject><subject>Aging - metabolism</subject><subject>Alzheimer's disease</subject><subject>Alzheimers disease</subject><subject>Apoptosis</subject><subject>Babies</subject><subject>Biology</subject><subject>Biomarkers - metabolism</subject><subject>Cancer</subject><subject>Catabolism</subject><subject>Correlation</subject><subject>Damage accumulation</subject><subject>Deoxyribonucleic acid</subject><subject>Depletion</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA repair</subject><subject>Electron transport</subject><subject>Enzymes</subject><subject>Female</subject><subject>Females</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Lipid Peroxidation</subject><subject>Lipids</subject><subject>Male</subject><subject>Males</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>NAD</subject><subject>NAD - metabolism</subject><subject>Nicotinamide</subject><subject>Nicotinamide adenine dinucleotide</subject><subject>Oxidation</subject><subject>Oxidative metabolism</subject><subject>Oxidative phosphorylation</subject><subject>Oxidative Stress</subject><subject>Peroxidation</subject><subject>Pharmacology</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Poly(ADP-ribose)</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Polymerase</subject><subject>Proteins</subject><subject>Repair</subject><subject>Ribose</subject><subject>Rodents</subject><subject>Sex Characteristics</subject><subject>Signaling</subject><subject>SIRT1 protein</subject><subject>Sirtuin 1 - metabolism</subject><subject>Skin</subject><subject>Surgery</subject><subject>Transporter</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkltv1DAQhSMEoqXwDxBE4gUJZfElduIXpFXLpVJVXuDZGtuTXa8Se7GTCv59s2xatQj5wZb9nTMz1imK15SsKG_ox12cUoB-tY8BV4TUjIvmSXFKFWeVZIQ_fXA-KV7kvCNE8FbK58UJY23dNpKcFtfrDVaQc7QeRnSl3ULYYC59KONv72D0N1jmMWHOJQRXXq8vPpQDjmBi7_Nw4LbTAKEcfc4TviyeddBnfLXsZ8XPL59_nH-rrr5_vTxfX1VWKDZWVKBzshNKGcYaJWknkTaMW8GdFWho07XWEM7RWOMMcOxsDZJ1pFUUa-Bnxduj776PWS9fkTXlTAjWSMFn4vJIuAg7vU9-gPRHR_D670VMGw1p9LZHLZRwkoCpW8RaktqoxvC2VS0VnRDk4PVpqTaZAZ3FMCboH5k-fgl-qzfxRvOaNJSp2eD9YpDirwnzqAefLfY9BIzT3DfhRMyL0hl99w_6_-nqI2VTzDlhd98MJfoQjzuVPsRDL_GYZW8eDnIvussDvwVIKLgy</recordid><startdate>20120727</startdate><enddate>20120727</enddate><creator>Massudi, Hassina</creator><creator>Grant, Ross</creator><creator>Braidy, Nady</creator><creator>Guest, Jade</creator><creator>Farnsworth, Bruce</creator><creator>Guillemin, Gilles J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120727</creationdate><title>Age-associated changes in oxidative stress and NAD+ metabolism in human tissue</title><author>Massudi, Hassina ; Grant, Ross ; Braidy, Nady ; Guest, Jade ; Farnsworth, Bruce ; Guillemin, Gilles J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c592t-15edd6f599b227961f6e1723c53dc5eb17f8cb033ebcbdba3efc4a62f0891e4a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenine</topic><topic>Adenosine diphosphate</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Aging</topic><topic>Aging - genetics</topic><topic>Aging - metabolism</topic><topic>Alzheimer's disease</topic><topic>Alzheimers disease</topic><topic>Apoptosis</topic><topic>Babies</topic><topic>Biology</topic><topic>Biomarkers - metabolism</topic><topic>Cancer</topic><topic>Catabolism</topic><topic>Correlation</topic><topic>Damage accumulation</topic><topic>Deoxyribonucleic acid</topic><topic>Depletion</topic><topic>DNA</topic><topic>DNA Damage</topic><topic>DNA repair</topic><topic>Electron transport</topic><topic>Enzymes</topic><topic>Female</topic><topic>Females</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Lipid Peroxidation</topic><topic>Lipids</topic><topic>Male</topic><topic>Males</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Mitochondria</topic><topic>NAD</topic><topic>NAD - metabolism</topic><topic>Nicotinamide</topic><topic>Nicotinamide adenine dinucleotide</topic><topic>Oxidation</topic><topic>Oxidative metabolism</topic><topic>Oxidative phosphorylation</topic><topic>Oxidative Stress</topic><topic>Peroxidation</topic><topic>Pharmacology</topic><topic>Phosphorylation</topic><topic>Physiology</topic><topic>Poly(ADP-ribose)</topic><topic>Poly(ADP-ribose) polymerase</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>Polymerase</topic><topic>Proteins</topic><topic>Repair</topic><topic>Ribose</topic><topic>Rodents</topic><topic>Sex Characteristics</topic><topic>Signaling</topic><topic>SIRT1 protein</topic><topic>Sirtuin 1 - metabolism</topic><topic>Skin</topic><topic>Surgery</topic><topic>Transporter</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Massudi, Hassina</creatorcontrib><creatorcontrib>Grant, Ross</creatorcontrib><creatorcontrib>Braidy, Nady</creatorcontrib><creatorcontrib>Guest, Jade</creatorcontrib><creatorcontrib>Farnsworth, Bruce</creatorcontrib><creatorcontrib>Guillemin, Gilles J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest_Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Database‎ (1962 - current)</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest advanced technologies &amp; aerospace journals</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Massudi, Hassina</au><au>Grant, Ross</au><au>Braidy, Nady</au><au>Guest, Jade</au><au>Farnsworth, Bruce</au><au>Guillemin, Gilles J</au><au>Polymenis, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age-associated changes in oxidative stress and NAD+ metabolism in human tissue</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-07-27</date><risdate>2012</risdate><volume>7</volume><issue>7</issue><spage>e42357</spage><epage>e42357</epage><pages>e42357-e42357</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Nicotinamide adenine dinucleotide (NAD(+)) is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD(+) also represents the sole substrate for the nuclear repair enzyme, 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. Human pelvic 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&lt;0.0001; r = 0.768) and inversely correlated with tissue NAD(+) levels (p = 0.0003; r = -0.639). These associations were less evident in females. A strong negative correlation was observed between NAD(+) levels and age in both males (p = 0.001; r = -0.706) and females (p = 0.01; r = -0.537). SIRT1 activity also negatively correlated with age in males (p = 0.007; r = -0.612) but not in females. Strong positive correlations were also observed between lipid peroxidation and DNA damage (p&lt;0.0001; r = 0.4962), and PARP activity and NAD(+) levels (p = 0.0213; r = 0.5241) in post pubescent males. This study provides quantitative evidence in support of the hypothesis that hyperactivation of PARP due to an accumulation of oxidative damage to DNA during aging may be responsible for increased NAD(+) catabolism in human tissue. The resulting NAD(+) depletion may play a major role in the aging process, by limiting energy production, DNA repair and genomic signalling.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22848760</pmid><doi>10.1371/journal.pone.0042357</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2012-07, Vol.7 (7), p.e42357-e42357
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1325527653
source Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central
subjects Adenine
Adenosine diphosphate
Adolescent
Adult
Age
Aged
Aging
Aging - genetics
Aging - metabolism
Alzheimer's disease
Alzheimers disease
Apoptosis
Babies
Biology
Biomarkers - metabolism
Cancer
Catabolism
Correlation
Damage accumulation
Deoxyribonucleic acid
Depletion
DNA
DNA Damage
DNA repair
Electron transport
Enzymes
Female
Females
Hospitals
Humans
Infant, Newborn
Lipid Peroxidation
Lipids
Male
Males
Medicine
Metabolism
Middle Aged
Mitochondria
NAD
NAD - metabolism
Nicotinamide
Nicotinamide adenine dinucleotide
Oxidation
Oxidative metabolism
Oxidative phosphorylation
Oxidative Stress
Peroxidation
Pharmacology
Phosphorylation
Physiology
Poly(ADP-ribose)
Poly(ADP-ribose) polymerase
Poly(ADP-ribose) Polymerases - metabolism
Polymerase
Proteins
Repair
Ribose
Rodents
Sex Characteristics
Signaling
SIRT1 protein
Sirtuin 1 - metabolism
Skin
Surgery
Transporter
Young Adult
title Age-associated changes in oxidative stress and NAD+ metabolism in human tissue
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T09%3A51%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Age-associated%20changes%20in%20oxidative%20stress%20and%20NAD+%20metabolism%20in%20human%20tissue&rft.jtitle=PloS%20one&rft.au=Massudi,%20Hassina&rft.date=2012-07-27&rft.volume=7&rft.issue=7&rft.spage=e42357&rft.epage=e42357&rft.pages=e42357-e42357&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0042357&rft_dat=%3Cproquest_plos_%3E2941554901%3C/proquest_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c592t-15edd6f599b227961f6e1723c53dc5eb17f8cb033ebcbdba3efc4a62f0891e4a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1325527653&rft_id=info:pmid/22848760&rfr_iscdi=true