Recombinant Klotho proteins, nucleic acids encoding the same, cell lines and cultures expressing the same, and method of manufacturing and administering the same are disclosed. Proteins have at least 80% amino acid sequence identity to a portion of human alpha Klotho and preferably a solubility or half-life-extending feature such as glycosylation and/or fusion protein tag. Treatment protocols include determining Klotho levels in a subject, calculating a dosage of the protein sufficient to raise the Klotho level in the subject to a predetermined level, administering the dosage to the subject, determining a rate of protein decline in the subject following administration of the protein, calculating a time and/or amount of a subsequent dosage of the protein, and/or administering the subsequent dosage to the subject. Proteins and related treatments for addressing aging-associated and other conditions are disclosed.
