Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase

Abstract

Ageing is characterised by the accumulation of molecular and cellular damage through time, leading to a decline in physical and mental abilities. Currently, society has experienced a rapid increase in life expectancy, which has led to an increase in age-associated diseases. Therefore, it is crucial to study the process of ageing to guarantee the best conditions in the final stages of life. In recent years, interest has increased in a myokine known as irisin, which is secreted during physical exercise. This polypeptide hormone is produced by various organs, mainly muscle, and once it is released into the blood, it performs a wide variety of functions that are involved in metabolic control and may be relevant during some of the diseases associated with ageing. The aim of this review is to highlight the recent studies of irisin, such as its mechanism of expression, blood release, distribution, tissue target and participation in various cellular metabolic reactions and the relationship with key anti-ageing pathways such as adenosine monophosphate-activated protein kinase, silent information regulator T 1, autophagy and telomerase. In conclusion, irisin is a key player during the ageing process and it could be a novel target molecule for the therapeutic approach to boost longevity pathways. However, more research will be necessary to use this promising hormone for this gain.

Keywords: AMPK; Ageing; SIRT1; autophagy; irisin; telomerase.

Fig. 1.

Schematic model of irisin production through physical exercise. Physical exercise leads to an increase in the transcriptional factor PGC1-α in skeletal muscle, which regulates the expression of the transmembrane protein FNDC5. This protein undergoes processing releasing the hormone irisin, a myokine induced by physical exercise that converts WAT into BAT, increasing thermogenesis and energy expenditure.

Fig. 2.

Schematic representation of the main signalling intracellular pathways activated by irisin. Irisin induces several cellular responses such as WAT browning, proliferation, neuroprotection, survival and longevity through the activation of ERK1/MAP-kinase, PI3K/AKT/Protein kinase B (PKB), AMP/PKA/CREB, AMPK/SIRT1/PGCα, autophagy and telomerase pathways.

Fig. 3.

Schematic representation of irisin's effect on molecular longevity pathways. Irisin levels increase after exposing to exercise or several pharmacological or nutraceutical treatments. The irisin released by the muscle has an autocrine effect on the muscle itself and an endocrine effect on many tissues such as adipose tissue, heart, liver, pancreas, lung or brain, improving metabolism and function. Between the pleiotropic effects of irisin some of them are mediated by stimulation of longevity pathways such as AMPK, SIRT1, autophagy and telomerase.