Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients

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.

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.

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).

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.