title: Age-Dependent Oxidative DNA Damage Does Not Correlate with Reduced Proliferation of Cardiomyocytes in Humans.
abstract: BACKGROUND
  Postnatal human cardiomyocyte proliferation declines rapidly with age, which has been suggested to be correlated with increases in oxidative DNA damage in mice and plays an important role in regulating cardiomyocyte proliferation. However, the relationship between oxidative DNA damage and age in humans is unclear.
  
  
  METHODS
  Sixty right ventricular outflow myocardial tissue specimens were obtained from ventricular septal defect infant patients during routine congenital cardiac surgery. These specimens were divided into three groups based on age: group A (age 0-6 months), group B (age, 7-12 months), and group C (>12 months). Each tissue specimen was subjected to DNA extraction, RNA extraction, and immunofluorescence.
  
  
  RESULTS
  Immunofluorescence and qRT-PCR analysis revealed that DNA damage markers-mitochondrial DNA copy number, oxoguanine 8, and phosphorylated ataxia telangiectasia mutated-were highest in Group B. However immunofluorescence and qRT-PCR demonstrated that two cell proliferation markers, Ki67 and cyclin D2, were decreased with age. In addition, wheat germ agglutinin-staining indicated that the average size of cardiomyocytes increased with age.
  
  
  CONCLUSIONS
  Oxidative DNA damage of cardiomyocytes was not correlated positively with age in human beings. Oxidative DNA damage is unable to fully explain the reduced proliferation of human cardiomyocytes.
authors.affiliation: Department of anesthesiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Institute of Pediatric Congenital Heart Diseases, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Haifa
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Institute of Pediatric Congenital Heart Diseases, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Institute of Pediatric Congenital Heart Diseases, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jinfen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Institute of Pediatric Congenital Heart Diseases, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Institute of Pediatric Congenital Heart Diseases, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Lincai
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jinghao
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000293:Adolescent; D000375:Aging / Q000502:physiology*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D056742:Cyclin D2 / Q000378:metabolism; D056915:DNA Copy Number Variations / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D004272:DNA, Mitochondrial; D019394:Ki-67 Antigen; C024829:8-hydroxyguanine; D006147:Guanine; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins