Background: Age‐associated sarcopenia is characterized of progressed loss of skeletal muscle power, mass, and function, which affects human physical activity and life quality. Besides, accompanied with sarcopenia, aged population also faces a series of metabolic dysfunctions. Irisin, the cleaved form of fibronectin type III domain‐containing protein 5 (FNDC5), is a myokine induced by exercise and has been shown to exert multiple beneficial effects on health. The goal of the study is to investigate the alterations of Fndc5/irisin in skeletal muscles during ageing and whether irisin administration could ameliorate age‐associated sarcopenia and metabolic dysfunction.Methods: The mRNA and protein levels of FNDC5/irisin in skeletal muscle and serum from 2‐ and 24‐month‐old mice or human subjects were analysed using qRT‐PCR and western blot. FNDC5/irisin knockout mice were generated to investigate the consequences of FNDC5/irisin deletion on skeletal muscle mass, as well as morphological and molecular changes in muscle during ageing via histological and molecular analysis. To identify the therapeutic effects of chronic irisin treatment in mice during ageing, in vivo intraperitoneal administration of 2 mg/kg recombinant irisin was performed three times per week in ageing mice (14‐month‐old) for 4 months or in aged mice (22‐month‐old) for 1 month to systematically investigate irisin's effects on age‐associated sarcopenia and metabolic performances, including grip strength, body weights, body composition, insulin sensitivity, energy expenditure, serum parameters and phenotypical and molecular changes in fat and liver.Results: We showed that the expression levels of irisin, as well as its precursor Fndc5, were reduced at mRNA and protein expression levels in muscle during ageing. In addition, via phenotypic analysis of FNDC5/irisin knockout mice, we found that FNDC5/irisin deficiency in aged mice exhibited aggravated muscle atrophy including smaller grip strength (−3.23%, P < 0.05), muscle weights (quadriceps femoris [QU]: −20.05%; gastrocnemius [GAS]: −17.91%; tibialis anterior [TA]: −19.51%, all P < 0.05), fibre size (QU: P < 0.01) and worse molecular phenotypes compared with wild‐type mice. We then delivered recombinant irisin protein intraperitoneally into ageing or aged mice and found that it could improve sarcopenia with grip strength (+18.42%, P < 0.01 or +13.88%, P < 0.01), muscle weights (QU: +9.02%, P < 0.01 or +16.39%, P < 0.05), fibre size (QU: both P < 0.05) and molecular phenotypes and alleviated age‐associated fat tissues expansion, insulin resistance and hepatic steatosis (all P < 0.05), accompanied with altered gene signatures.Conclusions: Together, this study revealed the importance of irisin in the maintenance of muscle physiology and systematic energy homeostasis during ageing and suggested a potent therapeutic strategy against age‐associated metabolic diseases via irisin administration.

Obesity is a multi-factor chronic disease caused by the mixed influence of genetics, environments and an imbalance of energy intake and expenditure. Due to life style changes, modern society sees a rapid increase in obesity occurrence along with aggravated risk of metabolic syndromes in population, including diabetes, hepatic steatosis, cardiovascular diseases and certain types of cancer. Although obesity has become a serious worldwide public health hazard, effective and safe drugs treating obesity are still missing. Traditional Chinese medicine (TCM) has been implicated in practical use in China for thousands of years and accumulated substantial front-line experience in treating various diseases. Compared to western medicine that features defined composition and clear molecular mechanism, TCM is consisted with complex ingredients from plants and animals and prescribed based on overall symptoms and collective experience. Because of their fundamental differences, TCM and western medicine were once considered irreconcilable. However, nowadays, sophisticated isolation technologies and deepened molecular understanding of the active ingredients of TCM are gradually bridging the two, enabling the identification of active TCM components for drug development under the western-style paradigms. Thus, studies on TCM open a new therapeutic avenue and show great potential in the combat against obesity, though challenges exist. In this review, we highlight six key candidate substances derived from TCM, including artemisinin, curcumin, celastrol, capsaicin, berberine and ginsenosides, to review their recent discoveries in the metabolic field, with special focus on their therapeutic efficacy and molecular mechanisms in treating obesity and metabolic diseases. In addition, we discuss the translational challenges and perspectives in implementing modern Chinese medicine into western pharmaceutical industry.