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 Fc 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. The Klotho fusion proteins are useful in the treatment and prevention of a variety of age-related conditions and metabolic disorders. In another embodiment, the fusion polypeptide comprises a FGF (such as FGF23), or a functionally active variant or derivative thereof； and a modified Fc 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.本發明係關於預防或治療年齡相關之病狀或代謝障礙的方法、套組及組合物。本發明之融合多肽包括FGF23或其活性片段。在一實施例中，該融合多肽包含(a)包含纖維母細胞生長因子23(FGF23)的多肽，或其功能活性變異體或衍生物，其中FGF23在Q156、C206及C244處中一或多個位置具有突變；及(b)具有降低對Fc-γ受體之親和力及/或增加之血清半衰期的經修飾之Fc片段，或包含Klotho蛋白質之至少一個細胞外子域的多肽，或其功能活性變異體或衍生物；及視情況存在之(c)連接子。Klotho融合蛋白質適用於治療及預防多種年齡相關之病狀及代謝障礙。在另一實施例中，該融合多肽包含FGF(諸如FGF23)或其功能活性變異體或衍生物；及經修飾之Fc片段或其功能活性變異體或衍生物。在該融合多肽之多個實施例中，FGF23具有可減少聚集及蛋白酶介導之裂解的突變。
