The present invention is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The Klotho fusion polypeptides of the invention include at least a Klotho protein or an active fragment thereof The Klotho fusion proteins are useful in the treatment and prevention of a variety of age-related conditions and metabolic disorders.

An antibody and/or binding fragment thereof, wherein the antibody and/or binding fragment thereof specifically binds to an epitope of a αKlotho polypeptide, optionally a folded αKiotho or optionally with a dissociation constant (K.sub.D) of about 2 nM or less, as measured by competitive ELISA assay, methods 0 of making and using to diagnose kidney diseases.

The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inducing β-Klotho, and or FGF21-like mediated signaling. In embodiments, the antigen binding proteins specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c.

Disclosed are Klotho variant proteins in which residue Glu414 and/or residue Asp238 is substituted with an amino acid different than L-Glu or L-Asp, respectively, as well as polynucleotides encoding the variant proteins, and the use thereof in therapy, especially for the treatment of cancers, especially breast cancer and pancreatic cancer.

Mutated Lactobacillus brevis strain 269Y β-glucuronidase enzymes with enhanced enzymatic activity at low pH (e.g., below pH 6.8), as well as enhanced thermostability as compared to wild type enzyme are provided. The enzymes of the invention advantageously allow for accurate analysis of bodily samples for the presence of drugs at low pH and in 30 minutes or less, as compared to the several hours needed using prior enzyme preparations. Methods of using the mutated enzymes for hydrolysis of glucuronide substrates, including opiates and benzodiazepines, are also provided.

A method of producing Klotho protein includes preparing a Klotho plasmid DNA vector, culturing cells, transfecting the cells with the Klotho plasmid DNA vector in a cell culture medium, growing the transfected cells, and harvesting the cell culture supernatant by removing the transfected cells. The Klotho plasmid DNA vector has a mammalian selection marker and a Klotho open reading frame. The cells are primary fibroblast cells and/or mesenchymal stromal cells. A method of manufacturing a cosmetic composition includes combining Klotho protein or the cell culture supernatant with a cosmetically acceptable vehicle. A method of treating a patient to improve the condition and appearance of aging skin includes topically administering the cosmetic composition to the patient. By upregulating the Klotho gene in vitro and incorporating the Klotho protein and growth factors into a composition, transepidermal water loss, skin atrophy, and free radical damage to the skin may be addressed.

Described herein are glucose sensors. The sensors are composed of host cells incorporating DNA devices specifically designed to produce fluorescence when the cells come into contact with glucose from a patient sample. Once the fluorescence has been quantified, it can be correlated with the amount of glucose present in the sample. Also described herein are extracts from the host cells that can sense and measure glucose levels in a patient. The devices and extracts disclosed herein are inexpensive but sensitive and accurate enough for use in both home and clinical testing situations. The devices and extracts disclosed herein are also useful for diagnosis of diabetes, pre-diabetes, or other diseases associated with elevated glucose levels.

The present disclosure relates to compositions and methods for modulating gene expression and in particular to DNA binding proteins and their use for increasing expression of Klotho. In some examples, the present disclosure provides an isolated or recombinant DNA binding protein comprising or attached to a transcriptional activation domain wherein the DNA binding protein binds to a target sequence within or near a Klotho gene.

Disclosed are products and methods for monitoring Klotho protein levels and for stabilizing Klotho protein in a mammalian blood sample, especially at room temperature or without freezing, for a period of time. Methods of detecting and quantifying Klotho protein levels, particularly endogenous and/or exogenous soluble alpha Klotho protein levels, methods of diagnosing Klotho protein deficiency, and methods of increasing Klotho protein levels or production, particularly endogenous and/or exogenous soluble alpha Klotho protein level(s), expression, or production, in a mammalian subject, and products useful in performing the same, including diagnostic kits and compositions for treating Klotho protein deficiency, are disclosed. Compositions are configured or formulated to augment natural soluble alpha Klotho protein production, attenuate Klotho protein damage or degradation, and/or supplement Klotho protein levels with exogenous, recombinant protein. Treatment methods and uses include administration of the compositions to human or non-human mammalian subjects.

The present application relates to sialylated glycoprotein compositions and methods of their use in treating various conditions and disorders.