title: Dysfunction of liver regeneration in aged liver after partial hepatectomy.
abstract: OBJECTIVE
  A remarkable feature of the liver is its regenerative capacity following partial hepatectomy. However, the regenerative capacity of many organs and tissues loses its natural ability to divide with aging. In this study, we investigated the association of aging with endoplasmic reticulum stress, the cell cycle, autophagy, and apoptosis-related genes during liver regeneration after hepatectomy.
  
  
  METHODS
  Balb/c 4-week and 40-week-old male mice were subjected to 70% hepatectomy. Animals were sacrificed at 24, 48, and 72 h after hepatectomy. Immunohistochemical stainings for proliferating cell nuclear antigen, LC3, Atg5, and caspase-3 were used to quantify protein expression. Real-time reverse transcription-polymerase chain reaction was used to detect p16, CHOP, LC3, Atg5, hepatocyte growth factor, cMet, cyclin D1, cyclin A2, and caspase-3 expression.
  
  
  RESULTS
  After hepatectomy, old group showed a lower survival rate and significantly lower expression of hepatocyte growth factor, cMet, cyclin D1, cyclin A2, proliferating cell nuclear antigen labeling index, and SMP30 compared with young group. The liver weight/body weight ratio was significantly lower at 48 h and 72 h after hepatectomy and was accompanied by markedly elevated levels of the liver cell injury markers, LC3 and caspase-3. Immunohistochemical results showed that LC3, Atg5, and caspase-3 protein expression were higher in old group than in young group.
  
  
  CONCLUSIONS
  These results revealed that impaired liver regeneration was due to aging, which was expressed by decreased cell cycle and increased autophagy and apoptosis. Therefore, understanding the molecular basis for aged liver regeneration might provide a new therapeutic option for old patients.
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Chinbold
authors: C
authors: Enkhbold
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Yuji
authors: Y
authors: Morine
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Tohru
authors: T
authors: Utsunomiya
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Satoru
authors: S
authors: Imura
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Tetsuya
authors: T
authors: Ikemoto
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Yusuke
authors: Y
authors: Arakawa
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Yu
authors: Y
authors: Saito
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Shinichiro
authors: S
authors: Yamada
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Daichi
authors: D
authors: Ishikawa
authors: Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Mitsuo
authors: M
authors: Shimada
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001835:Body Weight; D002453:Cell Cycle / Q000235:genetics; D056751:Cyclin A2 / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000235:genetics; D008099:Liver / Q000473:pathology / Q000503:physiopathology*; D008115:Liver Regeneration / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008807:Mice, Inbred BALB C; D009929:Organ Size
chemical_list: C508184:CCNA2 protein, mouse; C530105:Ccnd1 protein, mouse; D056751:Cyclin A2; C553307:HGF protein, mouse; D019938:Cyclin D1; D017228:Hepatocyte Growth Factor
keywords: ER stress; aging; autophagy; liver regeneration; partial hepatectomy