Disclosed herein are novel compositions and methods for the treatment of age-related diseases, mitochondrial diseases, the improvement of stress resistance, the improvement of resistance to hypoxia and the extension of life span. Also described herein are methods for the identification of agents useful in the foregoing methods.

Methods and compositions are provided for the treatment of diseases or disorders associated with mitochondrial dysfunction.

The invention relates to methods for treatment and prevention of cancer by administering agents that increase levels of NAD+, such as NAD+ precursors or agents involved in NAD+ biosynthesis.

Provided is a composition for improving, preventing, or treating inflammatory bowel disease including a NAMPT-derived peptide as an active ingredient. The NAMPT-derived peptide of the present disclosure may bind to TRL4 and/or CYBB competitively with extracellular NAMPT (eNAMPT) to inhibit NLRP3 inflammasome activation by the interaction of eNAMPT with TRL4 and/or CYBB, and the NAMPT-derived peptide of the present disclosure further includes a peptide targeting colon tissue to act directly on the colon, so that it is expected to be useful for the prevention or treatment of inflammatory bowel disease.

The present invention discloses a Nicotinamide phosphoribosyltransferase (nampt) mutant and use thereof. The present invention relates to a nicotinamide phosphoribosyltransferase (Nampt) mutant artificially obtained through genic site-directed mutation. An object of the present invention is to provide a Nampt mutant having a catalytic activity higher than that of a conventional wild type parent, wherein the enzymatic activity of the Nampt mutant provided in the present invention is 1.2-6.9 times of the enzymatic activity of the parent.

Enzyme-based systems and methods for synthesizing the NAD precursors NMN and NaMN are disclosed. Such methods and systems utilize a mutated form of phosphoribosylpyrophosphate synthetase (PRS) that is superactive and/or other enzyme or enzyme combinations that are immobilized onto a solid surface. The methods and systems substantially increase the efficiency and yield of NAD precursor synthesis.

The present invention provides a method for preparing nicotinamide mononucleotide (NMN) by biocatalysis. The method includes a step of catalytically reacting a plurality of raw materials including nicotinamide, ATP, and ribose in the presence of nicotinamide phosphoribosyltransferase (Nampt), ribose phosphate pyrophosphokinase, and ribokinase, to prepare the NMN.

Methods and compositions for preventing or treating peripheral neuropathy, cognitive deficits, inactivity, depression, chemotherapy and/or radiotherapy induced peripheral neuropathy and cognitive deficits, and improving cognitive performance, in a subject in need thereof are disclosed. The disclosed methods include the step of administering to the subject an effective amount of an agent that increases the level of NAD.sup.+ in the subject.

Disclosed herein are novel compositions and methods for the treatment of age-related diseases, mitochondrial diseases, the improvement of stress resistance, the improvement of resistance to hypoxia and the extension of life span. Also described herein are methods for the identification of agents useful in the foregoing methods. Methods and compositions are provided for the treatment of diseases or disorders associated with mitochondrial dysfunction. The invention relates to methods for treatment and prevention of cancer by administering agents that increase levels of NAD+, such as NAD+ precursors or agents involved in NAD+ biosynthesis.

The invention discloses a genetically engineered bacterium in which the gene encoding adenine deaminase on the genome of the bacterium is knocked out or/and the gene encoding the enzyme in the NAD.sup.+ anabolic pathway is integrated on the genome of the bacterium. The invention also discloses a construction method of the above-mentioned genetically engineered bacteria. The gene encoding adenine deaminase on the genome of the host strain is knocked out to obtain a strain with high NAD.sup.+ yield. Or the expression cassettes of the gene encoding the enzyme in the NAD.sup.+ synthesis pathway are constructed separately, and then the enzyme encoding The gene expression cassette is integrated into the genome of the host strain whose gene encoding adenine deaminase is knocked out to construct a strain with high NAD.sup.+ production. The application of the above genetically engineered bacteria is disclosed. A method of producing NAD.sup.+ is disclosed.

The present disclosure provides an innovative method for improving the enzyme activity of an NMN biosynthetic enzyme Nampt, and relates to the technical field of genetic engineering. A mutant protein of the present disclosure is obtained by firstly analyzing a target protein Nampt using two softwares FoldX and DeepDDG, and then predicting multiple key sites influencing the enzyme functions and finally performing the semi-rational design of the enzyme. In the examples of the present disclosure, 10 mutant strains are constructed using the designed primers according to the principle of point mutation, and 8 of the mutants have higher activity than a wild-type strain, in which the NMN yield of the mutant Nampt-V365L is increased by 62%, and the NMN yields of the mutants Nampt-S248A, Nampt-N164L, Nampt-S382M, Nampt-A245T and Nampt-A208G are increased by 34%, 27%, 27%, 22% and 17% respectively.

The present invention provides methods and compositions for enhancing efficacy of anti-hormone treatment, or for preventing cancer relapse or progression following treatment. The invention also provides methods for re-sensitizing or sensitizing treatment resistant cancer cells or patients with treatment-refractory cancer cells to continuing or starting anti-hormone treatment. Further provided in the invention are methods for prognosis or diagnosis of anti-hormone treatment effect or likelihood of cancer relapse or metastasis following anti-hormone treatment.