Identification of aging change and senescence markers using African turquoise killifish

Vertebrates grow and mature with age after birth (aging change), deteriorate (senescence), and eventually die. However, the long lifespan of most vertebrates makes it challenging to identify markers of aging change and senescence. Here, we leverage the short-lived vertebrate African Turquoise killifish (N. furzeri) to isolate molecular markers distinguishing aging change from senescence. N. furzeri lifespan was divided into growth (young), mature (adult), and senescent (old) stages based on biological parameters. Cellular and molecular changes continually increasing or decreasing with age from young to adult to old stages were defined as “aging change”, and changes specifically between adult and old stages as “senescence”. We discovered hepatic lipid droplets formed at birth and disappeared during the adult stage. Metabolome and gene expression analyses of the liver where the majority of changes occurred identified several metabolites and genes as aging change markers (e.g., methylhistidine, glutarylcarnitine, and γ-butyrobetaine) and senescence markers (e.g., creatine, homocitrulline, pipecolic acid, p21, htra1, and slc13a5 genes) providing insights into alternative mechanisms of aging and senescence that may be conserved. Thus, molecular markers reflecting aging change and senescence at the organ levels can be isolated using N. furzeri.