Dissecting cellular and molecular networks of aging and senescence in the human hippocampus
Aging affects the learning and memory functions of the hippocampus. Senescence is a cellular phenomenon that may contribute to aging, but how it presents in the human hippocampus remains unclear. We profiled post-mortem hippocampi across adulthood using spatial transcriptomics, single-nucleus transcriptomics, and high-plex immunofluorescence imaging to identify spatially resolved signatures of…
The hippocampus, a region of the brain crucial for learning and memory, experiences changes due to aging. Senescence, a cellular state linked to aging, is not yet fully understood in the human hippocampus. Researchers employed spatial transcriptomics, single-nucleus transcriptomics, and high-plex immunofluorescence imaging on post-mortem hippocampi from individuals of different ages to pinpoint spatially distinct aging and senescence signatures.
Distinct aging trajectories were observed in specific cell types and anatomical layers of the hippocampus. For instance, genes involved in inhibitory neuron synapses declined with age in the CA4 layer. Gene programs also changed in a sex-dependent manner, with a notable microglial and neurovascular program, rich in senescence-associated genes, being more prominent in females. This program includes numerous genes connected with senescence, such as the CDKN1A/p21 marker.
High-plex imaging corroborated these findings, revealing discrepancies between senescence phenotypes labeled by p16 and p21 markers. This study underscores how factors like anatomical location, cell type, and sex influence aging and senescence processes within the hippocampus.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
