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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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
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Summary: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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0042357