Metabolic profiling of accelerated aging ERCC1 d/- mice.
Aging is a fundamental biological process for which the mechanism is still largely unknown due to its complex and multifactorial nature. Animal models allow us to simplify this complexity and to study individual factors separately. As there are many causative links between DNA repair deficiency and aging, we studied the ERCC1(d/-) mouse, which has a modified ERCC1 gene, involved in the Nucleotide Excision Repair, and as a result has a premature aging phenotype. Profiling of these mice on different levels can give an insight into the mechanisms underlying the aging phenotype. In the current study, we have performed metabolic profiling of serum and urine of these mice in comparison to wild type and in relation to aging by (1)H NMR spectroscopy. Analysis of metabolic trajectories of animals from 8 to 20 weeks suggested that wild type and ERCC1(d/-) mutants have similar age-related patterns of changes; however, the difference between genotypes becomes more prominent with age. The main differences between these two genetically diverse groups of mice were found to be associated with altered lipid and energy metabolism, transition to ketosis, and attenuated functions of the liver and kidney.
Nevedomskaya
Ekaterina
E
Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
Meissner
Axel
A
Goraler
Sibel
S
de Waard
Monique
M
Ridwan
Yanto
Y
Zondag
Gerben
G
van der Pluijm
Ingrid
I
Deelder
André M
AM
Mayboroda
Oleg A
OA
D019588:Aging, Premature / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D055442:Metabolome; D051379:Mice; D015999:Multivariate Analysis; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D025341:Principal Component Analysis; D020543:Proteome / Q000378:metabolism; D044967:Serum / Q000737:chemistry; D014556:Urine / Q000737:chemistry
D004268:DNA-Binding Proteins; D020543:Proteome; D004720:Endonucleases; C499360:Ercc1 protein, mouse