Brown University

Gerwald Jogl

John M Sedivy

Alexandra D'ordine

Disclosed is a method for preventing, delaying or reversing age-associated inflammation, by administering to a patient in need thereof a therapeutically effective amount of at least one LINE 1 (L-1) endonuclease inhibitor. The age-associated inflammation is associated with an upregulation of L1, an accumulation of cytoplasmic L1 cDNA, an activation of an IFN-I response, and/or a reinforcement of a SASP pro-inflammatory state. The L1 EN inhibitor is administered in an amount sufficient to prevent or reverse at least one of the upregulation L1, the accumulation of cytoplasmic L1 cDNA, the activation of the IFN-I response, and/or the SASP pro-inflammatory state.

Compositions and methods for treating, preventing or reversing age-associated inflammation and disorders

Disclosed are methods for preventing, delaying or reversing age-associated inflammation, by administering to a patient in need thereof a therapeutically effective amount of at least one long interspersed nuclear element 1 (LINE-1, L1) endonuclease inhibitor (L1 EN inhibitor), either alone or in combination with at least one additional therapeutic agent. Effectiveness of the methods can be measured via biomarkers and/or by a decrease in symptoms compared to those symptoms before administration of the L1 EN inhibitor. Specific chemical structures of the L1 EN inhibitors are identified and shown herein.

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Pawtucket, RI, United States of America

Gerwald Jogl