TY - JOUR T1 - Natural and pathological aging distinctively impact the vomeronasal detection system and social behavior JF - bioRxiv DO - 10.1101/2022.08.31.505522 SP - 2022.08.31.505522 AU - Adrián Portalés AU - Pablo Chamero AU - Sandra Jurado Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/09/25/2022.08.31.505522.abstract N2 - Normal aging and many age-related disorders such as Alzheimer’s disease cause deficits in olfaction, however it is currently unknown how natural and pathological aging impact the detection of social odors which might contribute to the impoverishment of social behavior at old age further worsening overall health. Here, we investigated the effect of aging in the recognition of social cues and the display of social behavior. Our findings indicate that aging distinctively disrupts the processing of social olfactory cues decreasing social odor exploration, discrimination and habituation in both wild type senescent (2-year-old) mice and in 1-year-old double mutant model of Alzheimer’s disease (APP/PS1Het). Furthermore, social novelty was diminished in 1-year-old APP/PS1Het mice, indicating that alterations in the processing of social cues are accelerated during pathological aging. Analysis of the vomeronasal organ, the main gateway to pheromone-encoded information, indicated that natural and pathological aging distinctively reduce the neurogenic ability of the vomeronasal sensory epithelium. Cell proliferation remained majorly preserved in 1-year model of Alzheimer’s disease (APP/PS1Het), whereas naturally aged animals exhibited significant deficiencies in the number of mature, proliferative and progenitor cells. This study reveals fundamental differences in the cellular processes by which natural and pathological aging disrupt the exploration of social cues and social behavior.Competing Interest StatementThe authors have declared no competing interest.ADAlzheimer’s diseaseAOBAnterior olfactory bulbAPPAmyloid precursor proteinCVNO central zoneCTFCorrected total fluorescenceFFTFood finding testIVNO intermediate zoneIAIsoamyl acetateMVNO marginal zoneMOBMain olfactory bulbMOEMain olfactory epitheliumNSENon-sensory epitheliumOCTOptimal cutting temperatureOMPOlfactory marker proteinPCNAProliferative cell nuclear antigenPS1Presinilin-1SCLSupporting cell layerSox2SRY-box transcription factor 2VLVomeronasal lumenVNOVomeronasal organVSEVomeronasal epithelium ER -