Identification of Isthmin1 in the small annual fish, Nothobranchius guentheri, as a novel biomarker of aging and its potential rejuvenation activity.

Isthmin 1 (Ism1) has been shown to play roles in multiple biological processes including morphogenesis, hematopoiesis, antiviral immune response and suppression of tumor growth. However, it remains unknown if it plays any role in aging process. Here we showed for the first time that Ism1 was a new age-related biomarker, which decreased with age in fish, mice and humans. Interestingly, Ism1 was also useful to measure the "rejuvenated" age of fish Nothobranchius guentheri reversed by salidroside treatment and temperature reduction, providing additional evidence that Ism1 was an aging biomarker. In addition, we clearly showed that dietary intake of recombinant Ism1 had little effects on the body length and weight of aging N. guentheri, but it retarded the onset of age-related biomarkers and prolonged both the maximum and median lifespan of the fish. We also showed that Ism1 exerted its rejuvenation activity via the enhancement of antioxidant system. Collectively, our results indicate that Ism1 is not only is a novel biomarker of aging but also a potential rejuvenation factor capable of reversing aging of N. guentheri.