title: Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients.
abstract: OBJECTIVE
  Liver regeneration likely decreases with age by an, as yet, incompletely understood mechanism, restricting the extent of hepatectomy. We therefore analyzed the effect of aging on liver regeneration and investigated mechanisms associate with poor regeneration of human liver.
  
  
  METHODS
  We assessed 130 patients who underwent hepatectomy at our institute between 2005 and 2012. The patients were divided into two groups, a younger (age < 65 years, n = 59) and an older (age > 65 years, n = 71) group. The expression of hepatocyte growth factor (HGF), its ligand Met, and the senescence-related genes p16, SIRT1 and SMP30 were assessed by qRT-PCR. Simulated preoperative and 1 week and 6 month postoperative liver volumes were evaluated in 11 younger and 11 older patients using a 3D simulation imaging system. Regenerated liver volumes were calculated and compared with clinicopathological factors, and correlations between liver regeneration and gene expression were calculated.
  
  
  RESULTS
  HGF and Met expression was significantly lower, and p16 expression significantly higher in older than in younger patients (P < 0.05 each). Mean increases in liver volume after 6 months were significantly greater in younger than in older patients (396.5 mL, 45.6% vs 159.4 mL, 23.3%, P < 0.05) but did not differ significantly at 1 week. Furthermore, p16 expression was negatively correlated with liver regeneration in older patients (R = -0.67, P < 0.05).
  
  
  CONCLUSIONS
  Poor liver regeneration in older patients may be associated with the upregulation of senescence-related genes, such as p16, and the downregulation of regeneration-promoting genes, such as HGF and Met.
authors: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors: Chengzhan
authors: C
authors: Zhu
authors: Tetsuya
authors: T
authors: Ikemoto
authors: Tohru
authors: T
authors: Utsunomiya
authors: Shinichiro
authors: S
authors: Yamada
authors: Yuji
authors: Y
authors: Morine
authors: Satoru
authors: S
authors: Imura
authors: Yusuke
authors: Y
authors: Arakawa
authors: Chie
authors: C
authors: Takasu
authors: Daichi
authors: D
authors: Ishikawa
authors: Mitsuo
authors: M
authors: Shimada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C000614131:CDKN2A protein, human; D002135:Calcium-Binding Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C513323:RGN protein, human; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: HGF; Met; liver regeneration; p16; senescence