α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40199978", "kind": "science-record", "revision": 4, "content_hash": "sha256:74d190b97887b979955b793fde3c109a0183df84533888c9bd454efae47003e2", "created_at": "2026-11-01T20:30:22Z", "updated_at": "2026-11-01T22:56:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence.", "doi": "10.1038/s41598-025-92328-7", "pmid": "40199978", "authors": ["Yuchao Wang", "Yue Zheng", "Xiaoyu Liang", "Yun Chang", "Yanwu Liu", "Xian Cheng", "Meng Zhang", "Wenqing Gao", "Tong Li"], "journal": "Scientific reports", "year": 2025, "abstract": "Myocardial infarction (MI) has high morbidity and mortality, and the macrophage senescence-associated secretory phenotype (SASP) plays a central role in M1 healing. α-Lipoic acid (ALA) alleviates MI by regulating the function of macrophages, although the relationship between ALA and macrophage senescence remains unclear. To investigate macrophage SASP in MI, we performed single-cell RNA sequencing (scRNA-seq) on the GEO GSE163465 dataset, along with qPCR and western blot analyses to assess SASP expression in macrophages subjected to hypoxia and ALA treatment. Immunofluorescence was used to detect SASP distribution. Coculture and animal experiments were performed to assess the therapeutic effects of ALA on macrophage senescence and cardiomyocyte ischemic injury. scRNA-seq revealed an age-independent senescent propensity of macrophages in MI. Increased expression of H2A.X, CCL7, IL1β, and CDKN1A, along with decreased SOD2 expression, confirmed that macrophage SASP occurred after hypoxia, with oxidative stress and energy metabolism involved in the process. ALA inhibited the degradation of SIRT1 and promoted the Nrf2 nuclear translocation, alleviating macrophage senescence and myocardial ischemic injury. Age-independent macrophage SASP occurred during MI. Macrophage SASP was induced by ROS and mitochondrial dysfunction. ALA alleviated SASP by decreasing ROS generation and autophagy flux while increasing SIRT1 levels, and Nrf2 nuclear translocation. ALA ameliorated MI injury.", "claims": [{"id": "claim-method", "statement": "Data between groups were compared using an unpaired two-tailed Student’s t-test and one-way ANOVA using Prism 8 (GraphPad Software, La Jolla, CA, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40199978", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "Data between groups were compared using an unpaired two-tailed Student’s t-test and one-way ANOVA using Prism 8 (GraphPad Software, La Jolla, CA, USA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analysed during this study are included in this published article [and its supplementary information files].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40199978", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "All data generated or analysed during this study are included in this published article [and its supplementary information files]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40199978"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE163465"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE163465"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40199978", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-025-92328-7", "sha256": "sha256:f071a8d9a6bea8c29182b9a560dd3a3bc0fd043df6654badd4eaa1a7e78855fc", "bytes": 45783, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-025-92328-7", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11978910", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE163465", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE163465", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE163465", "version": null, "note": "All data generated or analysed during this study are included in this published article [and its supplementary information files].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analysed during this study are included in this published article [and its supplementary information files].", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4985022", "GSM4985023", "GSM4985024", "GSM4985025", "GSM5513773", "GSM5513774", "GSM5513775"], "sample_count": 7, "group_sizes": null, "group_sizes_basis": null, "platform": "24247", "taxon": "Mus musculus", "title": "Single-cell RNA sequencing reveals the temporal diversity and dynamics of cardiac immunity after myocardial infarction", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE163465 not downloaded", "asset:data:geo:GSE163465 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Data between groups were compared using an unpaired two-tailed Student’s t-test and one-way ANOVA using Prism 8 (GraphPad Software, La Jolla, CA, USA)."}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE163465"], "resolved_accessions": ["GSE163465"], "statements": ["All data generated or analysed during this study are included in this published article [and its supplementary information files]."], "basis": "The paper names GSE163465 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:40199978", "data:geo:GSE163465"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE163465"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:49:57Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12857, "completion_tokens": 1019, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40199978", "type": "paper", "label": "pmid:40199978"}, {"id": "source:pmid:40199978", "type": "manuscript", "label": "PMID 40199978 full text"}, {"id": "data:geo:GSE163465", "type": "dataset", "label": "GEO GSE163465"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40199978", "type": "paper", "label": "pmid:40199978"}, {"id": "source:pmid:40199978", "type": "manuscript", "label": "PMID 40199978 full text"}, {"id": "data:geo:GSE163465", "type": "dataset", "label": "GEO GSE163465"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40199978", "type": "extraction", "used": ["source:pmid:40199978"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE163465", "type": "accession_resolution", "used": ["data:geo:GSE163465"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40199978", "parent_hash": "sha256:2329dd2002323e4ce0facbfbfbaa157c36711e2dc8fe4534a67d44279be33b47", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE163465 licence not read", "asset:data:geo:GSE163465 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["estigate macrophage SASP in MI, we performed single-cell RNA sequencing (scRNA-seq) on the GEO GSE163465 dataset, al", "MI, we performed single-cell RNA sequencing (scRNA-seq) on the GEO GSE163465 dataset, along with qP", "enescence and cardiomyocyte ischemic injury. scRNA-seq revealed an age-independent senescent propen"], "order_basis": "paper_text_order:429", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["rophage SASP in MI, we performed single-cell RNA sequencing (scRNA-seq) on the GEO GSE163465 dataset, al"], "order_basis": "paper_text_order:441", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ages subjected to hypoxia and ALA treatment. Immunofluorescence was used to detect SASP distribution. Cocult"], "order_basis": "paper_text_order:621", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d verified. Adult experimental C57Bl/6J male mice were purchased from Charles River (Beijing, China", "): SHAM, SHAM + ALA, MI, and MI + ALA. An MI mouse model was established by ligating the left anterio", "nterior descending coronary artery. Briefly, mice were anesthetized by inhalation of isoflurane (5%", "): SHAM, SHAM + ALA, MI, and MI + ALA. An MI mouse model was established by ligating the left a"], "order_basis": "paper_text_order:1803", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Data between groups were compared using an unpaired two-tailed Student’s t-test and one-way ANOVA using Prism 8 (GraphPad Software, La Jolla, CA, USA)."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}