Biomarkers Related To Metabolic Age and Methods Using The Same

Abstract

Biomarkers relating to metabolic age are provided, as well as methods for using such biomarkers as biomarkers for determining metabolic age. In addition, methods for modulating the metabolic age of a subject are also provided. Also provided are suites of small molecule entities as biomarkers for metabolic age.

1 . A method for determining the metabolic age of a subject comprising the steps of:
 a) analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for metabolic age in the sample, wherein the one or more biomarkers are selected from Tables 2, 4, 5, 7, and/or 8 and combinations thereof; and   b) comparing the level(s) of the one or more biomarkers in the sample to metabolic age reference levels of the one or more biomarkers to determine the subject's metabolic age.   
     
     
         2 . The method of  claim 1 , wherein the one or more biomarkers are selected from the biomarkers in Tables 2, 7, and/or 8 and combinations thereof having p-values of less than 0.05 and/or those biomarkers in Tables 2, 4, 5, 7, and/or 8, and combinations thereof having q-values of less than 0.10. 
     
     
         3 . The method of  claim 1 , wherein the level(s) of the one or more biomarkers in the sample are compared to a biochemical age index to determine the subject's metabolic age. 
     
     
         4 . The method of  claim 1 , wherein levels of the one or more biomarkers in the sample are similar to metabolic age reference levels corresponding to an older chronological age are indicative of a negative metabolic age. 
     
     
         5 . The method of  claim 1 , wherein levels of the one or more biomarkers in the sample are similar to metabolic age reference levels corresponding to a younger chronological age are indicative of a positive metabolic age. 
     
     
         6 . The method of  claim 1 , wherein the biological sample is blood plasma and the one or more biomarkers are selected from Tables 2, 4, 5, 7, and/or 8, and combinations thereof. 
     
     
         7 . The method of  claim 1 , wherein the reference level(s) are tailored to a population selected from the group consisting of gender, race and combinations thereof. 
     
     
         8 . The method of  claim 1 , wherein said subject is a male subject and the biomarkers are selected from one or more biomarkers in Tables 4 and 7. 
     
     
         9 . The method of  claim 1 , wherein said subject is a female subject and the biomarkers are selected from one or more biomarkers in Tables 4 and 7. 
     
     
         10 . A method for producing a Biochemical Age Index (BAI) comprising the steps of:
 a) analyzing biological samples from a plurality of subjects to determine the level(s) of one or more first biomarkers that change with age;   b) combining the level(s) one or more second biomarkers that correlate with each of the one or more first biomarkers that change with age to generate one or more groups of biomarkers that change with age; and   c) generating a biochemical age index using the levels of each of the one or more groups of biomarkers.   
     
     
         11 . The method of  claim 10 , wherein the one or more first biomarkers or the one or more second biomarkers are selected from Tables 2, 4, 5, 7, and/or 8, and combinations thereof. 
     
     
         12 . The method of  claim 10 , wherein the biochemical age index is generated by plotting the levels of the one or more groups of biomarkers versus age of the plurality of subjects. 
     
     
         13 . The method of  claim 10 , wherein the biochemical age index is tailored to a population selected from the group consisting of gender populations and race populations. 
     
     
         14 . The method of  claim 10 , wherein the biological samples are obtained from male or female subjects. 
     
     
         15 . A method for modifying the metabolic age of a subject comprising the steps of:
 a) analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for metabolic age in the sample, wherein the one or more biomarkers are selected from Tables 2, 4, 5, 7, and/or 8 and combinations thereof;   b) comparing the level(s) of the one or more biomarkers in the sample to metabolic age reference levels of the one or more biomarkers to determine the subject's metabolic age; and   c) providing recommendations to modify the metabolic age of a subject through changes in diet, nutrition, lifestyle, and/or administration of metabolites.   
     
     
         16 . The method of  claim 15 , wherein the one or more biomarkers are selected from the biomarkers in Tables 2, 4, 5, 7, and/or 8 and combinations thereof having p-values of less than 0.05 and/or those biomarkers in Tables 2, 4, 5, 7, and/or 8, and combinations thereof having q-values of less than 0.10. 
     
     
         17 . The method of  claim 15 , wherein the metabolic age reference level(s) are tailored to a population selected from the group consisting of gender, race and combinations thereof. 
     
     
         18 . The method of  claim 17 , wherein the markers are selected from Tables 4 and/or 5. 
     
     
         19 . A method of assessing the efficacy of a composition for modulating metabolic age, comprising:
 a) analyzing a first biological sample from a subject having a first metabolic age and currently or previously being treated with a compound or composition to determine the level(s) of one or more biomarkers selected from Tables 2, 4, 5, 7, and/or 8, and   b) comparing the level(s) of the one or more biomarkers in the sample to biomarkers levels selected from the group consisting of (a) level(s) of the one or more biomarkers in a second biological sample from the subject obtained from the subject before being treated with the compound or composition, (b) metabolic age-positive reference levels of the one or more biomarkers, (c) metabolic age-negative reference levels of the one or more biomarkers, and (d) reference levels of the one or more biomarkers for a target metabolic age.   
     
     
         20 . The method of  claim 19 , wherein the target metabolic age reference levels correspond to the chronological age of the subject. 
     
     
         21 . The method of  claim 19 , wherein the reference level(s) are tailored to a population selected from the group consisting of gender, race and combinations thereof. 
     
     
         22 . The method of  claim 20 , wherein the method further comprises:
 c) identifying compositions capable of modulating metabolic age.   
     
     
         23 . A method for screening a test compound for activity in modulating the level of one or more biomarkers of metabolic age, comprising:
 a) contacting one or more cells with a test compound;   b) analyzing at least a portion of the one or more cells or a biological sample associated with the cells to determine the level(s) of one or more biomarkers of metabolic age selected from Tables 2, 7, and/or 8; and   c) comparing the level(s) of the one or more biomarkers with predetermined levels for the biomarkers to determine whether the composition modulated the level(s) of the one or more biomarkers.   
     
     
         24 . The method of  claim 23 , wherein the predetermined standard levels for the biomarkers are selected from the group of level(s) of one or more biomarkers in the one or more cells in the absence of the composition and one or more biomarkers in one or more control cells not contacted with the test compound. 
     
     
         25 . The method of  claim 23 , wherein the method is conducted in vitro or in vivo.