Spatiotemporal profiling reveals the impact of caloric restriction in the aging mammalian brain.
| Publication Type | Academic Article |
| Authors | Zhang Z, Epstein A, Schaefer C, Abdulraouf A, Jiang W, Zhou W, Cao J |
| Journal | Cell Rep |
| Volume | 44 |
| Issue | 9 |
| Pagination | 116165 |
| Date Published | 08/19/2025 |
| ISSN | 2211-1247 |
| Keywords | Caloric Restriction, Aging, Brain |
| 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. |
| DOI | 10.1016/j.celrep.2025.116165 |
| PubMed ID | 40833855 |
| PubMed Central ID | PMC12519563 |