Irisin Improves Autophagy of Aged Hepatocytes via Increasing Telomerase Activity in Liver Injury

An aged liver has decreased reparative capacity during ischemia-reperfusion (IR) injury. A recent study showed that plasma irisin levels predict telomere length in healthy adults. The aim of the present study is to clarify the role of irisin, telomerase activity, and autophagy during hepatic IR in the elderly. To study this, hepatic IR was established in 22-month- and 3-month-old rats and primary hepatocytes were isolated. The results showed that the old rats exhibited more serious liver injury and lower levels of irisin expression, telomerase activity, autophagy ability, and mitochondrial function than young rats during hepatic IR. Irisin activated autophagy and improved mitochondrial function via increasing telomerase activity in aged hepatocytes. Inhibition of telomerase activity by BIBP1532 abolished the protective role of irisin in hepatocytes during hypoxia and reoxygenation. Additionally, this study proved irisin increased the telomerase activity via inhibition of the phosphorylation of JNK during hepatic IR. Administration of exogenous irisin significantly mitigated the inflammation, oxidative stress, apoptosis, and liver injury in an old rat model of hepatic IR. In conclusion, irisin improves autophagy of aged hepatocytes via increasing telomerase activity in hepatic IR. Irisin exhibits conspicuous benefits in increasing reparative capacity of an aged liver during hepatic IR.