Identification of genetic markers of biological age and metabolism

Abstract

A method of measuring the biological age of a multicellular organism is disclosed. In one embodiment this method comprises the steps of obtaining a sample of nucleic acid isolated from the organism's organ, tissue or cell and determining the expression pattern of a panel of sequences within the nucleic acid that have been predetermined by either increase or decrease in response to biological aging of the organ, tissue or cell. A method of obtaining biomarkers of aging is also disclosed. This method comprises the step of comparing a gene expression profile of a young multicellular organism subject's organ, tissue or cells; a gene expression profile from a chronologically aged subject's organ, tissue or cell; and a gene expression profile from a chronologically aged but biologically younger subject's organ, tissue or cell and identifying gene expression alterations that are observed when comparing the young subjects and the chronologically aged subjects and are not observed or reduced in magnitude when comparing the young subjects and the chronologically aged but biologically younger subjects.

We claim:  
     
         1 . A method of measuring the biological age of a multicellular organism comprising the steps of: 
 (a) obtaining a sample of nucleic acid isolated from the organism's organ, tissue or cell, wherein the nucleic acid is RNA or a cDNA copy of RNA and    (b) determining the gene expression pattern of a panel of specific sequences within the nucleic acid pool described in (a) that have been predetermined to either increase or decrease in response to biological aging of the organ, tissue or cell, where the gene expression pattern comprises the relative level of mRNA or cDNA abundance for the panel of specific sequences.    
     
     
         2 . The method of  claim 1  wherein the expression patterns of at least ten sequences are determined in step (b).  
     
     
         3 . The method of  claim 2  wherein the expression patterns of at least 20 sequences are determined in step (b).  
     
     
         4 . The method of  claim 3  wherein the expression levels of at least 30 sequences are determined in step (b).  
     
     
         5 . The method of  claim 4  wherein the expression levels of at least 40 sequences are determined in step (b).  
     
     
         6 . The method of  claim 5  wherein the expression levels of at least 50 sequences are determined in step (b).  
     
     
         7 . The method of  claim 1  wherein the organism is a mammal.  
     
     
         8 . The method of  claim 7  wherein the mammal is slected from the group consisting of humans, rats and mice.  
     
     
         9 . The method of  claim 1  wherein the nucleic acid is isolated from a tissue selected from the group consisting of brain tissue, heart tissue, muscle tissue, skin, liver tissue, blood, skeletal muscle, lymphocytes and mucosa.  
     
     
         10 . The method of obtaining biomarkers of aging comprising the steps of: 
 (a) comparing a gene expression profile of a young multicellular organism subject's organ, tissue or cells; a gene expression profile from a biologically and chronologically aged subject's organ, tissue or cell; and a gene expression profile from a chronologically aged but biologically younger subject's organ, tissue or cell, and    (b) identifying gene expression alterations that are observed when comparing the young subjects and the chronologically and biologically aged subjects and are not observed or reduced in magnitude when comparing the young subjects and chronologically aged but biologically younger subjects.    
     
     
         11 . The method of  claim 10  wherein one uses high density oligonucleotide arrays comprising at least 5-10% of the subject's genes to compare the subjects gene expression profile.  
     
     
         12 . The method of  claim 10  wherein the gene expression profile indicates a two-fold or greater increase or decrease in the expression of certain genes in chronologically aged subjects.  
     
     
         13 . The method of  claim 10  wherein the gene expression profile indicated a 3-fold or greater increase or decrease in the expression of certain genes in chronologically aged subjects.  
     
     
         14 . The method of  claim 10  wherein the gene expression profile indicates a 4-fold or greater increase or decrease in the expression of certain genes in chronologically aged subjects.  
     
     
         15 . A method of measuring biological age of muscle tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers W08057, AA114576, 11071777, 11106112, D29016, and M16465.  
     
     
         16 . A method of measuring biological age of muscle tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers described in Tables 1, 2, 15, and 16.  
     
     
         17 . A method of measuring biological age of brain tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers M17440, K01347, AA116604 and X16995.  
     
     
         18 . The method of  claim 10  wherein the subject is a mammal.  
     
     
         19 . The method of  claim 18  wherein the mammal is selected from the group consisting of humans, mice and rats.  
     
     
         20 . A method of measuring biological age of brain tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers described in Tables 5, 6, 9, and  10 .  
     
     
         21 . A method of measuring biological age of heart tissue comprising the step of quantifying the mRNA abundance of a panel of biomarkers selected from the group consisting of markers described in Tables 11, 12, 13 and 14.  
     
     
         22 . A method for screening a compound for the ability to inhibit or retard the aging process in multicellular organisms tissue, organ or cell comprising the steps of: 
 (a) dividing test organisms into first and second mammalian samples;    (b) exposing the organisms of the first sample to a test compound;    (c) analyzing tissues, organs or cells of the first and second samples for the level of expression of a panel of sequences that have been predetermined to either increase or decrease in response to biological aging of the tissue;    (d) comparing the analysis of the first and second samples and identifying test compounds that modify the expression of the sequences of step (c) in the first sample such that the expression pattern is indicative of tissue, organ or cell that has an inhibited or retarded biological age.    
     
     
         23 . A method as in  claim 22 , wherein the organism is a mammal.  
     
     
         24 . The method of  claim 23 , wherein the mammal is selected from the group consisting of humans, rats and mice.  
     
     
         25 . A method as in  claim 23 , wherein the tissue is selected from the group consisting of brain tissue, heart tissue, muscle tissue, blood, skeletal muscle, mucosa, skin, lymphocytes and liver tissue.  
     
     
         26 . A method of detecting whether a test compound mimics the gene profile induced by caloric restriction, comprising the steps of: 
 (a) exposing a multicellular organism to the test compound, and    (b) measuring the expression level of a panel of sequences predetermined to either increase or decrease in response to biological aging in a tissue, organ or cell of the organism and comparing the measurement to a measurement obtained in the same tissue, organ or cell in calorically restricted subjects.    
     
     
         27 . The method of  claim 26  wherein the multicellular organism is a mammal.  
     
     
         28 . The method of  claim 27  wherein the mammal is selected from the group consisting of humans, rodents and mice.