Recombinant Klotho proteins and variants, nucleic acids encoding the same, cell lines and suspension cultures expressing the same, and method of manufacturing and administering the same are disclosed. Proteins include solubility or half-life-extending features like glycosylation and fusion protein tags. Proteins have at least 85% amino acid sequence identity to a portion of human alpha Klotho isoform 1. Treatment protocols include determining serum soluble Klotho level in a subject, calculating a dosage of the protein sufficient to raise the serum soluble Klotho level in the subject to a predetermined level, administering the dosage of protein to the subject, such as by bolus or gradual injection, determining a rate of Klotho protein decline in the serum of the subject following administration of the first dosage, calculating a time and amount of a subsequent dosage of the Klotho protein, and administering the subsequent dosage of Klotho protein to the subject.
