biostudies-literatureBonnifet TAgence Nationale de la RechercheFédération pour la Recherche sur le CerveauFONDATION ALZHEIMERFondation du Collège de FranceFondation de FranceInstitut de FranceRP100687https://www.ebi.ac.uk/biostudies/studies/S-EPMC12463392biostudies-literatureUnknown13Recent studies have established a reciprocal causal link between aging and the activation of transposable elements, characterized in particular by a de-repression of LINE-1 retrotransposons. These LINE-1 elements represent 21% of the human genome, but only a minority of these sequences retain the coding potential essential for their mobility. LINE-1 encoded proteins can induce cell toxicity implicated in aging and neurodegenerative diseases. However, our knowledge of the expression and localization of LINE-1-encoded proteins in the central nervous system is limited. Using a novel approach combining atlas-based brain mapping with deep-learning algorithms on large-scale pyramidal brain images, we unveil a heterogeneous, neuron-predominant, and widespread ORF1p expression throughout the murineLifeSteady-state neuron-predominant LINE-1 encoded ORF1p protein and LINE-1 RNA increase with aging in the mouse and human brain.PMC12463392ANR-20-CE16-0022 NEURAGEFondation NRJ00086320Massiani-Beaudoin OLoew DFuchs JSinnassamy SMonnet HJoshi RLMailly PLombard BServant NBonnifet TfalseSteady-state neuron-predominant LINE-1 encoded ORF1p protein and LINE-1 RNA increase with aging in the mouse and human brain.Recent studies have established a reciprocal causal link between aging and the activation of transposable elements, characterized in particular by a de-repression of LINE-1 retrotransposons. These LINE-1 elements represent 21% of the human genome, but only a minority of these sequences retain the coding potential essential for their mobility. LINE-1 encoded proteins can induce cell toxicity implicated in aging and neurodegenerative diseases. However, our knowledge of the expression and localization of LINE-1-encoded proteins in the central nervous system is limited. Using a novel approach combining atlas-based brain mapping with deep-learning algorithms on large-scale pyramidal brain images, we unveil a heterogeneous, neuron-predominant, and widespread ORF1p expression throughout the murin2025-01-01T00:00:00Z2025 Sep2026-06-03T21:11:09.42Z2026-05-01T03:11:06.687ZS-EPMC124633924099679110.7554/eLife.100687