{"doi":"10.1016/j.celrep.2025.116165","title":"Spatiotemporal profiling reveals the impact of caloric restriction in the aging mammalian 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.","journal":"Cell Reports","year":2025,"id":546174,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7644,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1022233,"name":"Alexander E. Epstein","orcid":"0000-0002-7784-9040","position":1,"is_corresponding":false},{"id":1022234,"name":"Chloe Schaefer","orcid":"0009-0008-2913-9352","position":2,"is_corresponding":false},{"id":806450,"name":"Abdulraouf Abdulraouf","orcid":"0000-0003-4452-4781","position":3,"is_corresponding":false},{"id":1031347,"name":"Weirong Jiang","orcid":null,"position":4,"is_corresponding":false},{"id":250225,"name":"Wei Zhou","orcid":"0000-0003-4236-4091","position":5,"is_corresponding":false},{"id":94703,"name":"Junyue Cao","orcid":"0000-0003-4097-489X","position":6,"is_corresponding":false},{"id":1022236,"name":"Zehao Zhang","orcid":"0000-0002-7568-5775","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:53:32.285899Z","pmid":"40833855","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}