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

Abstract

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.

Telomere length: how the length makes a difference

“…Moreover, it was shown that normal physiological aging could be delayed without increasing the incidence of cancer, as demonstrated in adult wild-type mice (pharmacological activation or systemic viral transduction of telomerase) [31,32]. As shown in an old rat model, telomerase induction mediated by irisin (a secreted myokine) was accompanied by autophagy induction and improved mitochondrial function in aged hepatocytes [33]. Another telomerase activator, TA-65 (extracted from Astragalus Membranaceus) that is capable of increasing average telomere length and decreasing the percentage of critically short telomeres, was studied in a mouse model.…”

Irisin Mitigates Oxidative Stress, Chondrocyte Dysfunction and Osteoarthritis Development through Regulating Mitochondrial Integrity and Autophagy

“…Irisin is a soluble peptide cleaved from the extracellular domain of FNDC5, regulating the apoptotic program or autophagic reaction in various cell types [23,32]. The analyses of decreased FNDC5 signaling in osteoarthritic chondrocytes in human OA prompted us to isolate Irisin recombinant proteins and verify whether the gained Irisin function changed knee OA development.…”

The Role of Autophagy for the Regeneration of the Aging Liver

“…Recently, several studies indicated that autophagy is substantially lower in the aged liver compared to the young liver [5,[14][15][16]. Aging leads to a decrease in the number and function of autophagosomes and causes lipofuscin accumulation.…”