Molecular signatures of conditions associated with longevity

Abstract

The invention provides a collection of gene expression signatures that is linked to longevity. Also provided herein are assays, methods, and systems for identifying a treatment that can modulate lifespan or determining an effect of a treatment on a health profile of a subject by using the collection of gene expression signatures described herein.

What is claimed is: 
     
         1 . A collection of (i) gene expression signatures as set forth in  FIG. 4 ,  FIG. 5 ,  FIG. 9 , or Table 5, or a combination thereof that are upregulated, and (ii) gene expression signatures as set forth in  FIG. 4 ,  FIG. 5 ,  FIG. 9 , or Table 5, or a combination thereof that are downregulated. 
     
     
         2 . A method of screening a treatment that affects a health profile of a subject, the method comprising:
 (a) administering the treatment to the subject or a cell obtained from the subject; and   (b) measuring, in a sample obtained from the subject or the cell, an effect of the treatment on the expression of at least 10 genes of (i) a collection of gene expression signatures as set forth in  FIG. 4 ,  FIG. 5 ,  FIG. 9 , or Table 5, or a combination thereof that are upregulated, (ii) a collection of gene expression signatures as set forth in  FIG. 4 ,  FIG. 5 ,  FIG. 9 , or Table 5, or a combination thereof that are downregulated, or a combination of (i) and (ii) as compared to a reference.   
     
     
         3 . The method of  claim 2 , wherein the treatment comprises administration of an agent, a lifestyle change, a change in disease status, or a combination thereof. 
     
     
         4 . The method of  claim 3 , wherein the agent comprises a small molecule, a peptide, a peptidomimetic, an RNA interference molecule, an antibody, an aptamer, or a gene therapy. 
     
     
         5 . The method of  claim 4 , wherein the agent is a geroprotector. 
     
     
         6 . The method of  claim 3 , wherein the lifestyle change comprises a change in exercise status, a dietary change, a change in smoking status, a change in alcohol or substance use, a change in stress levels, or a combination thereof. 
     
     
         7 . The method of  claim 2 , wherein the reference is a gene expression profile of the at least 10 genes of the subject prior to the treatment. 
     
     
         8 . The method of  claim 2 , wherein the subject is a mammal 
     
     
         9 . The method of  claim 8 , wherein the mammal is a human. 
     
     
         10 . An assay for identifying a treatment that can modulate lifespan, the assay comprising:
 (a) administering a treatment to a cell, cell line, or mammal;   (b) measuring, in the cell, cell line or a biological sample obtained from the mammal, a gene expression profile of at least 10 genes of (i) a collection of gene expression signatures as set forth in  FIG. 4 ,  FIG. 5 ,  FIG. 9 , or Table 5, or a combination thereof that are upregulated, (ii) a collection of gene expression signatures as set forth in  FIG. 4 ,  FIG. 5 ,  FIG. 9 , or Table 5, or a combination thereof that are downregulated, or a combination of (i) and (ii);   (c) comparing the gene expression profile of the at least 10 genes with a reference longevity signature, wherein if the gene expression profile is at least 75% similar to the reference longevity signature, the treatment is predicted to increase lifespan, and wherein if the gene expression profile is less than 75% similar to the reference longevity signature, the treatment is predicted to have no effect on lifespan or decrease lifespan.   
     
     
         11 . The assay of  claim 10 , wherein the treatment comprises administration of an agent, a lifestyle change, a change in disease status, or a combination thereof. 
     
     
         12 . The assay of  claim 11 , wherein the agent comprises a small molecule, a peptide, a peptidomimetic, an RNA interference molecule, an antibody, an aptamer, or a gene therapy. 
     
     
         13 . The assay of  claim 12 , wherein the agent is a geroprotector. 
     
     
         14 . The assay of  claim 11 , wherein the lifestyle change comprises a change in exercise status, a dietary change, a change in smoking status, a change in alcohol or substance use, a change in stress levels, or a combination thereof. 
     
     
         15 . The assay of  claim 10 , wherein the reference longevity signature comprises a gene expression profile of at least one mammal having a long lifespan. 
     
     
         16 . The assay of  claim 10 , wherein step (b) comprises measuring the gene expression profile of at least 20 genes, at least 100 genes, at least 500 genes, or at least 1000 genes. 
     
     
         17 . The assay of  claim 10 , wherein the biological sample comprises whole blood, plasma, serum, liver, kidney or brain tissue. 
     
     
         18 . The assay of  claim 10 , wherein the mammal is a human.