{"doi":"10.64898/2025.12.13.694109","title":"DNA methylation signatures of frailty beyond age: a longitudinal study of female and male mice","abstract":"= 49), measured frailty index and derived DNA methylation data from PBMCs. We selected frailty-related differentially methylated CpGs and determined differentially methylated regions (DMRs), focusing on both age-independent and -dependent frailty, and using both mixed-sex and sex-stratified subgroups. We propose a joint set of 925 frailty-related DMRs, perform an association study with frailty outcomes, build epigenetic frailty clocks and validate in mice with interventions. Notably, age-independent frailty DMRs are enriched in nervous and endocrine pathways, distinct from signaling and lipid metabolism pathways identified from age-dependent DMRs. We observe hypermethylation in signaling pathways and hypomethylation in lipid metabolism and cytochrome P450 pathways with frailty progression. 36 DMRs show consistent associations in validation. These findings highlight distinct epigenetic signatures underlying frailty and aging, with potential sex-specific mechanisms.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":585442,"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":0.0,"corpus_rank":10352,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8775,"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":50.0,"fair_percentile":62.69020085209982,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":857302,"name":"Shyleen Frost","orcid":"0000-0002-4421-1980","position":1,"is_corresponding":false},{"id":806986,"name":"Patrick Griffin","orcid":"0000-0002-8241-7381","position":2,"is_corresponding":false},{"id":106660,"name":"Maeve S. McNamara","orcid":"0000-0001-9043-0212","position":3,"is_corresponding":false},{"id":106661,"name":"David Sinclair","orcid":"0000-0002-9936-436X","position":4,"is_corresponding":false},{"id":218499,"name":"Alice E. Kane","orcid":"0000-0002-4303-0491","position":5,"is_corresponding":false},{"id":1400930,"name":"Dantong Zhu","orcid":"0000-0003-0875-0490","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:59:20.067334Z","pmid":"41446098","pmcid":"PMC12724424","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":50.0,"fair_a":81.25,"fair_i":0.0,"fair_r":41.6667,"fair_zscore":0.6165,"fair_rationale":{"fair_score":50.0,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":50.0,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"Mice metadata, DNA methylation data, and R markdown file for data analysis are available at https://github.com/Kane-Lab-ISB/Longitudinal-DNA-methylation-analysis-in-mice .","grounded":true,"rationale":"The only identifier given is a GitHub URL, which is not a persistent identifier scheme. 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[majority verdict 'yes' (4/5 passes agreed)]","anchors":["RDA-A1.1-01D — 'Data is accessible through a free access protocol'","FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","NSTC Desirable Characteristics of Data Repositories (2022) — 'Free and Easy Access'"],"scored":true,"signal":null},{"key":"a_access_conditions_stated","label":"Access level labelled","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"The raw datasets will be deposited in the Gene Expression Omnibus (GEO) and released publicly upon publication of the manuscript.","grounded":true,"rationale":"The paper states that the data will be 'released publicly', which is an explicit access-level label. 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[majority verdict 'partial' (4/5 passes agreed)]","anchors":["NIH DMS Plan Element 4 (NOT-OD-21-014) — Data Preservation, Access, and Associated Timelines","NSTC Desirable Characteristics (2022), Organizational Infrastructure: 'Retention Policy'","RDA-A2-01M — 'Metadata is guaranteed to remain available after data is no longer available'"],"scored":false,"signal":null}]},"I":{"name":"Interoperable","score":0.0,"criteria":[{"key":"i_open_nonproprietary_format","label":"Open file format","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No file format is named for the released data.","anchors":["FsF-R1.3-02D — F-UJI: 'Data is available in a file format recommended by the target research co","RDA-R1.3-02D — data is expressed in a machine-understandable community standard","RDA-I1-01D — data uses a knowledge representation expressed in a standardised format"],"scored":true,"signal":null},{"key":"i_community_standard_vocabulary","label":"Community standard / vocabulary","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No community data standard (e.g., MIAME, controlled vocabulary) is named for the data.","anchors":["RDA-R1.3-01M — 'Metadata complies with a community standard' (priority Essential)","RDA-R1.3-01D — 'Data complies with a community standard'","RDA-I2-01M — '(Meta)data use vocabularies that follow FAIR principles'"],"scored":false,"signal":null},{"key":"i_qualified_references","label":"Identifiers for the resources the data depend on","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No identifier for a source dataset, database, or external resource is given. [majority verdict 'no' (4/5 passes agreed)]","anchors":["RDA-I3-01M — '(meta)data include references to other (meta)data'","RDA-I3-03M — 'metadata includes qualified references to other metadata'","FsF-I3-01M — F-UJI: 'Metadata includes links between the data and its related entities'"],"scored":false,"signal":null}]},"R":{"name":"Reusable","score":41.67,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No license is named for the data; the CC-BY license on the article does not apply to the data.","anchors":["RDA-R1.1-01M — 'Metadata includes information about the licence under which the data can be reu","RDA-R1.1-02M — 'Metadata refers to a standard reuse licence'","RDA-R1.1-03M — 'Metadata refers to a machine-understandable reuse licence'"],"scored":true,"signal":null},{"key":"r_provenance_methods","label":"Provenance of the data","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"samples were then processed by FOXO Technologies using the Infinium Mouse Methylation BeadChip (Illumina, CA, USA).","grounded":true,"rationale":"The paper names the specific microarray platform (Infinium Mouse Methylation BeadChip). 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[majority verdict 'yes' (4/5 passes agreed)]","anchors":["NIH DMS Policy Element 2 (NOT-OD-21-014) — 'Related Tools, Software and/or Code'","FAIR4RS Principles v1.0 (Chue Hong et al., 2022; RDA/FORCE11/ReSA) — FAIR Principles for Resear","FORCE11 Software Citation Principles (Smith, Katz & Niemeyer, 2016, PeerJ CS 2:e86)"],"scored":true,"signal":null},{"key":"x_funding_attribution","label":"Funder and award number","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"A.E.K is supported by NIH/NIA R00AG070102 and a generous gift from Daniel T. Ling and Lee Obrzut. D.A.S is supported by R01AG019719 and R21HG011850, the Glenn Foundation for Medical Research and the Milky Way Research Foundation.","grounded":true,"rationale":"Grant numbers are provided for the funding. [majority verdict 'yes' (4/5 passes agreed)]","anchors":["DataCite Metadata Schema 4.6 — 'FundingReference' property (funderName, funderIdentifier, award","Crossref Funder Registry — canonical funder identifiers for funding metadata","RDA-F2-01M — rich metadata provided to allow discovery (funding is part of the descriptive reco"],"scored":true,"signal":null}]}},"actions":[{"key":"r_reuse_license","dimension":"R","label":"Reuse licence","action":"Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 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A dataset that needs a €2,000 licence to open is not reusable.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format is named for the released data.","gain":8.33,"priority":"important","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Mice metadata, DNA methylation data, and R markdown file for data analysis are available at https://github.com/Kane-Lab-ISB/Longitudinal-DNA-methylation-analysis-in-mice .","why":"The dataset identifier (GitHub URL) appears only in the body text, not in the reference list. 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This is the only DAS class associated with a measured citation advantage; 'available on reasonable request' and 'within the article' are not.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Mice metadata, DNA methylation data, and R markdown file for data analysis are available at https://github.com/Kane-Lab-ISB/Longitudinal-DNA-methylation-analysis-in-mice .","why":"The statement points to a GitHub URL, which is not a repository record with an accession or DOI. [majority verdict 'partial' (3/5 passes agreed)]","gain":0.0,"priority":"essential","scored":false},{"key":"f_discovery_metadata","dimension":"F","label":"Description of the dataset as an object","action":"Add a 'Data Records' section: itemise every file in the deposit and every variable or sample it holds, with counts and units. 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[majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"The raw datasets will be deposited in the Gene Expression Omnibus (GEO) and released publicly upon publication of the manuscript.","why":"The paper states when the data will become available (upon publication) but does not state how long they will persist. [majority verdict 'partial' (4/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false}],"suggestions":["Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","Mint or cite a persistent identifier for the dataset — a repository DOI or an accession from a registered repository — and print it in the paper. A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication.","Deposit the data in a repository registered in re3data/FAIRsharing (a domain repository such as GEO, SRA, dbGaP, PRIDE, or a generalist such as Zenodo, Dryad, Dataverse) and name it explicitly in the paper. A lab website is not an archive: it has no retention commitment and no accession.","Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable.","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-07-20T13:49:52.850455Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}