Rusty Gage Links LINE-1 Retrotransposon Activity to Neuronal Aging and Alzheimer's Disease

Rusty Gage described how LINE-1 retrotransposons, about 40% of the human genome, are silenced in mature neurons as RNA condensates that dissolve with aging, freeing LINE-1 RNA to trigger cGAS-STING inflammation and neuronal senescence. His team derived neurons from patient fibroblasts in about three weeks, preserving donor age, with a skin biopsy bank from 150 healthy elderly and Alzheimer's and mild cognitive impairment donors. Reverse transcriptase inhibitors such as 3TC reduced inflammation in AD-derived neurons in vitro, mouse model tests are under way, and Gage expects AD-related human trials within about two years.