Spatiotemporal profiling reveals the impact of caloric restriction in the aging mammalian brain

Summary: Caloric restriction (CR) is a well-studied intervention that extends lifespan and slows cognitive decline across species, yet the specific cell populations and molecular pathways involved remain elusive. In this study, we profiled >500,000 cells from 36 control and CR mouse brains across...

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Bibliographic Details
Main Authors: Zehao Zhang, Alexander Epstein, Chloe Schaefer, Abdulraouf Abdulraouf, Weirong Jiang, Wei Zhou, Junyue Cao
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725009362
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Summary:Summary: Caloric restriction (CR) is a well-studied intervention that extends lifespan and slows cognitive decline across species, yet the specific cell populations and molecular pathways involved remain elusive. In this study, we profiled >500,000 cells from 36 control and CR mouse brains across three age groups with EasySci single-nucleus transcriptomics and performed imaging-free IRISeq spatial transcriptomics on twelve brain sections from CR and control aged mice. We thereby explored the impact of CR in >300 cellular states and 11 brain regions. CR delayed expansion of inflammatory cell populations, preserved neural precursor cells, and broadly reduced the expression of aging-associated genes involved in cellular stress, senescence, inflammation, and DNA damage. CR restored the expression of region-specific genes linked to cognitive function, myelin maintenance, and circadian rhythm. In summary, we provide a high-resolution spatiotemporal map of the aging mouse brain’s response to CR, detailing precise cellular and molecular mechanisms behind its neuroprotective effects.
ISSN:2211-1247