RT Journal Article SR Electronic T1 Single cell analysis of the aging hypothalamus JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.07.434282 DO 10.1101/2021.03.07.434282 A1 Hajdarovic, Kaitlyn H. A1 Yu, Doudou A1 Hassell, Lexi-Amber A1 Evans, Shane A1 Neretti, Nicola A1 Webb, Ashley E. YR 2021 UL http://biorxiv.org/content/early/2021/03/08/2021.03.07.434282.abstract AB Alterations in metabolism, sleep patterns, body composition, and hormone status are all key features of aging. The hypothalamus is a well-conserved brain region that controls these homeostatic and survival-related behaviors. Despite the importance of this brain region in healthy aging, little is known about the intrinsic features of hypothalamic aging. Here, we utilize single nuclei RNA-sequencing to assess the transcriptomes of 22,718 hypothalamic nuclei from young and aged female mice. We identify cell type-specific signatures of aging in neurons, astrocytes, and microglia, as well as among the diverse collection of neuronal subtypes in this region. We uncover key changes in cell types critical for metabolic regulation and body composition, as well as in an area of the hypothalamus linked to cognition. In addition, our analysis reveals female-specific changes in sex chromosome regulation in the aging brain. This study identifies critical cell-specific features of the aging hypothalamus in mammals.Competing Interest StatementThe authors have declared no competing interest.