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

Zehao Zhang, Alexander Epstein, Chloe Schaefer, Abdulraouf Abdulraouf, Weirong Jiang, Wei Zhou, Junyue Cao

Laboratory of Single-Cell Genomics and Population Dynamics, The Rockefeller University, New York, NY, USA; The David Rockefeller Graduate Program in Bioscience, The Rockefeller University, New York, NY, USA.Laboratory of Single-Cell Genomics and Population Dynamics, The Rockefeller University, New York, NY, USA; The David Rockefeller Graduate Program in Bioscience, The Rockefeller University, New York, NY, USA. · pubmed

Paper

Abstract

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.

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Research summary

The study demonstrates that caloric restriction can delay aging-related changes in the brain by preserving specific cell populations and reducing the expression of aging-associated genes. This research is relevant as it explores mechanisms that could contribute to lifespan extension and cognitive health, addressing root causes of aging rather than merely treating symptoms.

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