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:	Hassina Massudi, Ross Grant, Nady Braidy, Jade Guest, Bruce Farnsworth, Gilles J Guillemin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/595d60ab48ee4604b97b3889815f5503
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spelling	oai:doaj.org-article:595d60ab48ee4604b97b3889815f55032021-11-18T07:10:32ZAge-associated changes in oxidative stress and NAD+ metabolism in human tissue.1932-620310.1371/journal.pone.0042357https://doaj.org/article/595d60ab48ee4604b97b3889815f55032012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22848760/?tool=EBIhttps://doaj.org/toc/1932-6203Nicotinamide 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.Hassina MassudiRoss GrantNady BraidyJade GuestBruce FarnsworthGilles J GuilleminPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e42357 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hassina Massudi Ross Grant Nady Braidy Jade Guest Bruce Farnsworth Gilles J Guillemin Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.
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.
format	article
author	Hassina Massudi Ross Grant Nady Braidy Jade Guest Bruce Farnsworth Gilles J Guillemin
author_facet	Hassina Massudi Ross Grant Nady Braidy Jade Guest Bruce Farnsworth Gilles J Guillemin
author_sort	Hassina Massudi
title	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_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_sort	age-associated changes in oxidative stress and nad+ metabolism in human tissue.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/595d60ab48ee4604b97b3889815f5503
work_keys_str_mv	AT hassinamassudi ageassociatedchangesinoxidativestressandnadmetabolisminhumantissue AT rossgrant ageassociatedchangesinoxidativestressandnadmetabolisminhumantissue AT nadybraidy ageassociatedchangesinoxidativestressandnadmetabolisminhumantissue AT jadeguest ageassociatedchangesinoxidativestressandnadmetabolisminhumantissue AT brucefarnsworth ageassociatedchangesinoxidativestressandnadmetabolisminhumantissue AT gillesjguillemin ageassociatedchangesinoxidativestressandnadmetabolisminhumantissue
_version_	1718423852741033984

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

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