Transposon Activation During Aging and Neuronal Decline

Abstract

The present invention relates to transposon activation and mobilization, particularly in the brain, during normal aging; reporter systems to detect such mobilization, along with cells and transgenic animals containing such systems; methods of monitoring neuronal function during normal aging; methods of determining the risk of age-related neuronal decline and age-related mortality; and the use of transposon inhibitors and apoptosis inhibitors to delay age-related neuronal decline and age-related mortality.

1 - 80 . (canceled) 
     
     
         81 . A method of delaying age-related neuronal decline, comprising administering to a subject in need of such treatment an effective amount of a transposon inhibitor. 
     
     
         82 . The method of  claim 81 , wherein the transposon inhibitor is an inhibitor of a protein encoded by a transposon. 
     
     
         83 . The method of  claim 82 , wherein the protein encoded by the transposon is a transposase; an integrase; a reverse transcriptase; an endonuclease; a protein encoded by gag, pol, or env; an enzyme encoded by ORF1 of a non-LTR transposon; or an enzyme encoded by ORF2 of a non-LTR transposon. 
     
     
         84 . The method of  claim 81 , wherein the transposon inhibitor is an anti-retroviral drug; an inhibitor of reverse transcription; an inhibitor of transposase or integrase activity; an inhibitor of endonuclease activity; a zinc-finger that targets a transposon promoter region; a repressor that inhibits a transposon; an innate antiretroviral resistance factor; a small interfering RNAs (siRNA), short hairpin RNA (shRNA), morpholino, or antisense oligonucleotide directed to a TE transcript; or an inhibitor of post-translational processing or proteolysis of a transposon-encoded protein. 
     
     
         85 . The method of  claim 81 , wherein the transposon inhibitor is an inhibitor of a retrotransposon. 
     
     
         86 . The method of  claim 85 , wherein the retrotransposon is an LTR retrotransposon. 
     
     
         87 . The method of  claim 86 , wherein the LTR transposon includes a gypsy element. 
     
     
         88 . The method of  claim 85 , wherein the retrotransposon is a non-LTR retrotransposon. 
     
     
         89 . The method of  claim 88 , wherein the non-LTR retrotransposon is a LINE-like element. 
     
     
         90 . The method of  claim 89 , wherein the LINE-like element is R1 or R2. 
     
     
         91 . The method of  claim 88 , wherein the non-LTR retrotransposon is a LINE element. 
     
     
         92 . The method of  claim 91 , wherein the LINE element is L1. 
     
     
         93 . The method of  claim 88 , wherein the non-LTR retrotransposon is a SINE retrotransposon. 
     
     
         94 . The method of  claim 93 , wherein the SINE retrotransposon is an Alu sequence. 
     
     
         95 . The method of  claim 81 , wherein the transposon inhibitor is an inhibitor of reverse transcriptase activity. 
     
     
         96 . The method of  claim 81 , wherein the transposon inhibitor is an inhibitor of endonuclease activity. 
     
     
         97 . The method of  claim 81 , wherein the transposon inhibitor is an inhibitor of integrase activity. 
     
     
         98 . The method of  claim 81 , wherein the transposon inhibitor is an anti-retroviral drug.