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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...

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Autores principales: Massudi, Hassina, Grant, Ross, Braidy, Nady, Guest, Jade, Farnsworth, Bruce, Guillemin, Gilles J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407129/
https://www.ncbi.nlm.nih.gov/pubmed/22848760
http://dx.doi.org/10.1371/journal.pone.0042357
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author Massudi, Hassina
Grant, Ross
Braidy, Nady
Guest, Jade
Farnsworth, Bruce
Guillemin, Gilles J.
author_facet Massudi, Hassina
Grant, Ross
Braidy, Nady
Guest, Jade
Farnsworth, Bruce
Guillemin, Gilles J.
author_sort Massudi, Hassina
collection PubMed
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<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<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.
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spelling pubmed-34071292012-07-30 Age-Associated Changes In Oxidative Stress and NAD(+) Metabolism In Human Tissue Massudi, Hassina Grant, Ross Braidy, Nady Guest, Jade Farnsworth, Bruce Guillemin, Gilles J. PLoS One Research Article 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<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<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. Public Library of Science 2012-07-27 /pmc/articles/PMC3407129/ /pubmed/22848760 http://dx.doi.org/10.1371/journal.pone.0042357 Text en © 2012 Massudi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Massudi, Hassina
Grant, Ross
Braidy, Nady
Guest, Jade
Farnsworth, Bruce
Guillemin, Gilles J.
Age-Associated Changes In Oxidative Stress and NAD(+) Metabolism In Human Tissue
title Age-Associated Changes In Oxidative Stress and NAD(+) Metabolism In Human Tissue
title_full Age-Associated Changes In Oxidative Stress and NAD(+) Metabolism In Human Tissue
title_fullStr Age-Associated Changes In Oxidative Stress and NAD(+) Metabolism In Human Tissue
title_full_unstemmed Age-Associated Changes In Oxidative Stress and NAD(+) Metabolism In Human Tissue
title_short Age-Associated Changes In Oxidative Stress and NAD(+) Metabolism In Human Tissue
title_sort age-associated changes in oxidative stress and nad(+) metabolism in human tissue
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407129/
https://www.ncbi.nlm.nih.gov/pubmed/22848760
http://dx.doi.org/10.1371/journal.pone.0042357
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