The present disclosure is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The fusion polypeptides of the disclosure include FGF23 or an active fragment thereof. In one embodiment, the fusion polypeptide comprises (a) a polypeptide comprising fibroblast growth factor 23 (FGF23), or a functionally active variant or derivative thereof, wherein FGF23 has a mutation at one or more of the positions Q156, C206 and C244； and (b) either a modified Fe fragment having decreased affinity for Fc-gamma-receptor and/or increased serum half-life, or a polypeptide comprising at least one extracellular subdomain of a Klotho protein, or a functionally active variant or derivative thereof； and, optionally (c) a linker. In another embodiment, the fusion polypeptide comprises a FGF (such as FGF23), or a functionally active variant or derivative thereof； and a modified Fe fragment, or a functionally active variant or derivative thereof. In various embodiments of the fusion polypeptides, FGF23 has mutations which decrease aggregation and protease-mediated cleavage.
