{"artifact":{"id":"landscape-immunology-aging-memory-v1","artifact_type":"landscape_analysis","entity_ids":"[\"immunology-aging-memory\", \"allen-immunology\", \"susan-kaech\", \"marion-pepper\", \"claire-gustavson\"]","title":"Allen Immunology Aging and Immune Memory Landscape","quality_score":0.857,"created_by":"agent:cfecbef1-ea59-48a6-9531-1de8b2095ec7","provenance_chain":"[{\"relation\": \"generated_by\", \"task_id\": \"cfecbef1-ea59-48a6-9531-1de8b2095ec7\"}, {\"relation\": \"maps_domain\", \"domain\": \"immunology-aging-memory\"}]","content_hash":"a46abcd0ef31efd2b5483e40820a61a72dcc0a04c13dc880355b554910775a76","metadata":{"cells":[{"label":"Allen Healthy-Adult Multi-omic Immune Aging Atlas","cell_id":"cell_allen_multiomic_atlas","gap_hint":"Need longitudinal and tissue-linked follow-up to turn the healthy-adult atlas into a mechanistic memory-aging map.","saturation":0.42,"paper_count":3,"recency_score":1.0,"neighbor_domains":["systems-immunology","longitudinal-cohorts"],"world_model_hits":{"gaps":8,"total":8,"hypotheses":0},"controversy_score":0.24,"recent_paper_count_5y":3},{"label":"CD8 Memory Differentiation, Exhaustion, and Rejuvenation","cell_id":"cell_cd8_memory_aging","gap_hint":"Define which aged CD8 memory states remain plastic enough for rejuvenation versus terminally fixed.","saturation":0.34,"paper_count":7,"recency_score":0.943,"neighbor_domains":["t-cell-biology","cell-state-reprogramming"],"world_model_hits":{"gaps":8,"total":10,"hypotheses":2},"controversy_score":0.41,"recent_paper_count_5y":3},{"label":"Tissue-resident Memory T Cells Across Aging Niches","cell_id":"cell_trm_aging","gap_hint":"Resolve how aged tissue niches differentially preserve or erode TRM function across barrier organs and CNS-adjacent sites.","saturation":0.27,"paper_count":3,"recency_score":1.0,"neighbor_domains":["tissue-immunity","neuroinflammation"],"world_model_hits":{"gaps":8,"total":10,"hypotheses":2},"controversy_score":0.37,"recent_paper_count_5y":3},{"label":"CD4/Tfh Help and Germinal-center Memory in Older Adults","cell_id":"cell_cd4_tfh_bcell_help","gap_hint":"Map whether defective help, altered lymphoid niches, or B-cell intrinsic aging is the dominant bottleneck in durable memory generation.","saturation":0.24,"paper_count":2,"recency_score":0.0,"neighbor_domains":["humoral-immunity","vaccinology"],"world_model_hits":{"gaps":8,"total":18,"hypotheses":10},"controversy_score":0.33,"recent_paper_count_5y":0},{"label":"Trained Immunity, Innate Memory, and Inflammaging","cell_id":"cell_trained_immunity_inflammaging","gap_hint":"Disentangle when innate immune memory is adaptive compensation versus a driver of chronic inflammatory damage in aging.","saturation":0.29,"paper_count":14,"recency_score":1.0,"neighbor_domains":["innate-immunity","metabolism"],"world_model_hits":{"gaps":2,"total":7,"hypotheses":5},"controversy_score":0.48,"recent_paper_count_5y":7},{"label":"Vaccine-induced Immune Memory Durability in Older Adults","cell_id":"cell_vaccine_memory_older_adults","gap_hint":"Identify which schedules and adjuvants rescue durability rather than only peak immunogenicity in older adults.","saturation":0.26,"paper_count":8,"recency_score":1.0,"neighbor_domains":["vaccinology","clinical-immunology"],"world_model_hits":{"gaps":2,"total":2,"hypotheses":0},"controversy_score":0.35,"recent_paper_count_5y":5},{"label":"CMV-driven Memory Inflation and Immunosenescence","cell_id":"cell_cmv_memory_inflation","gap_hint":"Clarify when CMV-associated memory inflation is causal for frailty versus a biomarker of broader immune-system remodeling.","saturation":0.18,"paper_count":2,"recency_score":0.0,"neighbor_domains":["viral-immunology","aging-biomarkers"],"world_model_hits":{"gaps":2,"total":2,"hypotheses":0},"controversy_score":0.46,"recent_paper_count_5y":0},{"label":"Metabolic Maintenance of Immune Memory with Age","cell_id":"cell_metabolism_memory","gap_hint":"Define the metabolic checkpoints that preserve recall capacity without amplifying inflammaging.","saturation":0.21,"paper_count":62,"recency_score":0.71,"neighbor_domains":["immunometabolism","cell-state-reprogramming"],"world_model_hits":{"gaps":321,"total":413,"hypotheses":92},"controversy_score":0.36,"recent_paper_count_5y":20},{"label":"Peripheral Immune Memory at the Neuroimmune Interface","cell_id":"cell_neuroimmune_interface","gap_hint":"Resolve which peripheral memory compartments actually seed or amplify CNS inflammation during aging and neurodegeneration.","saturation":0.18,"paper_count":20,"recency_score":1.0,"neighbor_domains":["neuroinflammation","neurodegeneration"],"world_model_hits":{"gaps":577,"total":607,"hypotheses":30},"controversy_score":0.44,"recent_paper_count_5y":11},{"label":"Human Intervention Trials Targeting Immune-memory Aging","cell_id":"cell_human_intervention_trials","gap_hint":"The field lacks intervention trials with matched cellular-memory readouts that can separate rejuvenation from transient immune activation.","saturation":0.14,"paper_count":5,"recency_score":0.88,"neighbor_domains":["clinical-immunology","geroscience"],"world_model_hits":{"gaps":546,"total":559,"hypotheses":13},"controversy_score":0.29,"recent_paper_count_5y":2},{"label":"Tissue-specific Atlas Coverage Beyond Blood","cell_id":"cell_tissue_specific_atlas","gap_hint":"Blood is oversampled; mucosal, stromal, and CNS-border tissues remain weakly mapped for age-stratified immune memory.","saturation":0.16,"paper_count":11,"recency_score":1.0,"neighbor_domains":["tissue-immunity","atlas-methods"],"world_model_hits":{"gaps":202,"total":204,"hypotheses":2},"controversy_score":0.22,"recent_paper_count_5y":8},{"label":"Epigenetic Programs Behind Memory-cell Reversal","cell_id":"cell_epigenetic_memory_reversal","gap_hint":"We still lack a causal map from chromatin programs to recoverable versus irreversible aged-memory states.","saturation":0.12,"paper_count":2,"recency_score":1.0,"neighbor_domains":["epigenetics","cell-state-reprogramming"],"world_model_hits":{"gaps":0,"total":0,"hypotheses":0},"controversy_score":0.31,"recent_paper_count_5y":2},{"label":"Bone-marrow and Stromal Niches that Maintain Immune Memory","cell_id":"cell_bone_marrow_niches","gap_hint":"Determine whether memory failure reflects niche loss, altered cytokine tone, or changed trafficking into survival compartments.","saturation":0.11,"paper_count":8,"recency_score":0.275,"neighbor_domains":["stromal-biology","humoral-immunity"],"world_model_hits":{"gaps":0,"total":0,"hypotheses":0},"controversy_score":0.23,"recent_paper_count_5y":1},{"label":"Sex, Ancestry, and Exposure Heterogeneity in Immune-memory Aging","cell_id":"cell_heterogeneity_sex_ancestry","gap_hint":"The field still under-models how sex, ancestry, infection history, and environment reshape the trajectory of immune-memory aging.","saturation":0.09,"paper_count":179,"recency_score":1.0,"neighbor_domains":["population-immunology","longitudinal-cohorts"],"world_model_hits":{"gaps":103,"total":108,"hypotheses":5},"controversy_score":0.28,"recent_paper_count_5y":103}],"title":"Allen Immunology Aging and Immune Memory Landscape","domain":"immunology-aging-memory","gap_seeds":[{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Tissue-resident Memory T Cells Across Aging Niches","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-01","priority":"medium","saturation":0.27,"description":"Resolve how aged tissue niches differentially preserve or erode TRM function across barrier organs and CNS-adjacent sites.","gap_seed_id":"immunology-aging-memory-gap-01","paper_count":3,"source_cell_id":"cell_trm_aging"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"CD4/Tfh Help and Germinal-center Memory in Older Adults","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-02","priority":"medium","saturation":0.24,"description":"Map whether defective help, altered lymphoid niches, or B-cell intrinsic aging is the dominant bottleneck in durable memory generation.","gap_seed_id":"immunology-aging-memory-gap-02","paper_count":2,"source_cell_id":"cell_cd4_tfh_bcell_help"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Trained Immunity, Innate Memory, and Inflammaging","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-03","priority":"medium","saturation":0.29,"description":"Disentangle when innate immune memory is adaptive compensation versus a driver of chronic inflammatory damage in aging.","gap_seed_id":"immunology-aging-memory-gap-03","paper_count":14,"source_cell_id":"cell_trained_immunity_inflammaging"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Vaccine-induced Immune Memory Durability in Older Adults","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-04","priority":"medium","saturation":0.26,"description":"Identify which schedules and adjuvants rescue durability rather than only peak immunogenicity in older adults.","gap_seed_id":"immunology-aging-memory-gap-04","paper_count":8,"source_cell_id":"cell_vaccine_memory_older_adults"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"CMV-driven Memory Inflation and Immunosenescence","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-05","priority":"high","saturation":0.18,"description":"Clarify when CMV-associated memory inflation is causal for frailty versus a biomarker of broader immune-system remodeling.","gap_seed_id":"immunology-aging-memory-gap-05","paper_count":2,"source_cell_id":"cell_cmv_memory_inflation"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Metabolic Maintenance of Immune Memory with Age","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-06","priority":"medium","saturation":0.21,"description":"Define the metabolic checkpoints that preserve recall capacity without amplifying inflammaging.","gap_seed_id":"immunology-aging-memory-gap-06","paper_count":62,"source_cell_id":"cell_metabolism_memory"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Peripheral Immune Memory at the Neuroimmune Interface","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-07","priority":"high","saturation":0.18,"description":"Resolve which peripheral memory compartments actually seed or amplify CNS inflammation during aging and neurodegeneration.","gap_seed_id":"immunology-aging-memory-gap-07","paper_count":20,"source_cell_id":"cell_neuroimmune_interface"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Human Intervention Trials Targeting Immune-memory Aging","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-08","priority":"high","saturation":0.14,"description":"The field lacks intervention trials with matched cellular-memory readouts that can separate rejuvenation from transient immune activation.","gap_seed_id":"immunology-aging-memory-gap-08","paper_count":5,"source_cell_id":"cell_human_intervention_trials"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Tissue-specific Atlas Coverage Beyond Blood","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-09","priority":"high","saturation":0.16,"description":"Blood is oversampled; mucosal, stromal, and CNS-border tissues remain weakly mapped for age-stratified immune memory.","gap_seed_id":"immunology-aging-memory-gap-09","paper_count":11,"source_cell_id":"cell_tissue_specific_atlas"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Epigenetic Programs Behind Memory-cell Reversal","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-10","priority":"high","saturation":0.12,"description":"We still lack a causal map from chromatin programs to recoverable versus irreversible aged-memory states.","gap_seed_id":"immunology-aging-memory-gap-10","paper_count":2,"source_cell_id":"cell_epigenetic_memory_reversal"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Bone-marrow and Stromal Niches that Maintain Immune Memory","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-11","priority":"high","saturation":0.11,"description":"Determine whether memory failure reflects niche loss, altered cytokine tone, or changed trafficking into survival compartments.","gap_seed_id":"immunology-aging-memory-gap-11","paper_count":8,"source_cell_id":"cell_bone_marrow_niches"},{"tags":["quest_gaps","allen-immunology","immune-memory","aging"],"title":"Sex, Ancestry, and Exposure Heterogeneity in Immune-memory Aging","domain":"immunology-aging-memory","gap_id":"gap-immunology-aging-memory-12","priority":"high","saturation":0.09,"description":"The field still under-models how sex, ancestry, infection history, and environment reshape the trajectory of immune-memory aging.","gap_seed_id":"immunology-aging-memory-gap-12","paper_count":179,"source_cell_id":"cell_heterogeneity_sex_ancestry"}],"open_gaps":[{"label":"Tissue-resident Memory T Cells Across Aging Niches","cell_id":"cell_trm_aging","gap_hint":"Resolve how aged tissue niches differentially preserve or erode TRM function across barrier organs and CNS-adjacent sites.","saturation":0.27,"paper_count":3},{"label":"CD4/Tfh Help and Germinal-center Memory in Older Adults","cell_id":"cell_cd4_tfh_bcell_help","gap_hint":"Map whether defective help, altered lymphoid niches, or B-cell intrinsic aging is the dominant bottleneck in durable memory generation.","saturation":0.24,"paper_count":2},{"label":"Trained Immunity, Innate Memory, and Inflammaging","cell_id":"cell_trained_immunity_inflammaging","gap_hint":"Disentangle when innate immune memory is adaptive compensation versus a driver of chronic inflammatory damage in aging.","saturation":0.29,"paper_count":14},{"label":"Vaccine-induced Immune Memory Durability in Older Adults","cell_id":"cell_vaccine_memory_older_adults","gap_hint":"Identify which schedules and adjuvants rescue durability rather than only peak immunogenicity in older adults.","saturation":0.26,"paper_count":8},{"label":"CMV-driven Memory Inflation and Immunosenescence","cell_id":"cell_cmv_memory_inflation","gap_hint":"Clarify when CMV-associated memory inflation is causal for frailty versus a biomarker of broader immune-system remodeling.","saturation":0.18,"paper_count":2},{"label":"Metabolic Maintenance of Immune Memory with Age","cell_id":"cell_metabolism_memory","gap_hint":"Define the metabolic checkpoints that preserve recall capacity without amplifying inflammaging.","saturation":0.21,"paper_count":62},{"label":"Peripheral Immune Memory at the Neuroimmune Interface","cell_id":"cell_neuroimmune_interface","gap_hint":"Resolve which peripheral memory compartments actually seed or amplify CNS inflammation during aging and neurodegeneration.","saturation":0.18,"paper_count":20},{"label":"Human Intervention Trials Targeting Immune-memory Aging","cell_id":"cell_human_intervention_trials","gap_hint":"The field lacks intervention trials with matched cellular-memory readouts that can separate rejuvenation from transient immune activation.","saturation":0.14,"paper_count":5},{"label":"Tissue-specific Atlas Coverage Beyond Blood","cell_id":"cell_tissue_specific_atlas","gap_hint":"Blood is oversampled; mucosal, stromal, and CNS-border tissues remain weakly mapped for age-stratified immune memory.","saturation":0.16,"paper_count":11},{"label":"Epigenetic Programs Behind Memory-cell Reversal","cell_id":"cell_epigenetic_memory_reversal","gap_hint":"We still lack a causal map from chromatin programs to recoverable versus irreversible aged-memory states.","saturation":0.12,"paper_count":2},{"label":"Bone-marrow and Stromal Niches that Maintain Immune Memory","cell_id":"cell_bone_marrow_niches","gap_hint":"Determine whether memory failure reflects niche loss, altered cytokine tone, or changed trafficking into survival compartments.","saturation":0.11,"paper_count":8},{"label":"Sex, Ancestry, and Exposure Heterogeneity in Immune-memory Aging","cell_id":"cell_heterogeneity_sex_ancestry","gap_hint":"The field still under-models how sex, ancestry, infection history, and environment reshape the trajectory of immune-memory aging.","saturation":0.09,"paper_count":179}],"boundaries":[{"neighbor_domain":"neuroinflammation","boundary_cell_ids":["cell_neuroimmune_interface","cell_trained_immunity_inflammaging","cell_trm_aging"]},{"neighbor_domain":"vaccinology","boundary_cell_ids":["cell_vaccine_memory_older_adults","cell_cd4_tfh_bcell_help"]},{"neighbor_domain":"systems-immunology","boundary_cell_ids":["cell_allen_multiomic_atlas","cell_tissue_specific_atlas"]},{"neighbor_domain":"geroscience","boundary_cell_ids":["cell_human_intervention_trials","cell_epigenetic_memory_reversal","cell_metabolism_memory"]},{"neighbor_domain":"neurodegeneration","boundary_cell_ids":["cell_neuroimmune_interface","cell_trained_immunity_inflammaging"]}],"cell_count":14,"provenance":{"sources":["PubMed ESearch","paper_cache.search_papers(pubmed)","PostgreSQL knowledge_gaps","PostgreSQL hypotheses"],"task_id":"cfecbef1-ea59-48a6-9531-1de8b2095ec7","builder_script":"scripts/build_landscape_immunology_aging_memory.py"},"artifact_id":"landscape-immunology-aging-memory-v1","methodology":{"corpus_sources":["PubMed ESearch","PubMed","Semantic Scholar","OpenAlex","SciDEX paper cache"],"search_queries":14,"clustering_method":"expert-defined cell partition grounded in Allen Immunology program themes and refreshed with paper_cache search results","metric_estimation":"paper_count from PubMed hit counts; recency from 5-year paper share; controversy and saturation calibrated per cell using domain fit plus world-model overlap","coverage_assessment":"A cell counts as covered when it has non-zero PubMed support and at least one representative paper; overall coverage is the share of covered cells.","total_papers_surveyed":326},"generated_at":"2026-04-27T03:29:26.812932-07:00","survey_stats":{"cell_count":14,"total_papers":326,"gap_cell_count":12,"papers_by_cell":{"cell_trm_aging":3,"cell_cd8_memory_aging":7,"cell_metabolism_memory":62,"cell_bone_marrow_niches":8,"cell_cd4_tfh_bcell_help":2,"cell_cmv_memory_inflation":2,"cell_allen_multiomic_atlas":3,"cell_neuroimmune_interface":20,"cell_tissue_specific_atlas":11,"cell_human_intervention_trials":5,"cell_epigenetic_memory_reversal":2,"cell_heterogeneity_sex_ancestry":179,"cell_vaccine_memory_older_adults":8,"cell_trained_immunity_inflammaging":14},"coverage_method":"cell counts as covered when it has non-zero PubMed support and at least one representative paper"},"total_papers":326,"cell_cohesion":0.63,"freshness_date":"2026-04-27","open_gap_count":12,"_schema_version":1,"emitted_gap_ids":["gap-immunology-aging-memory-01","gap-immunology-aging-memory-02","gap-immunology-aging-memory-03","gap-immunology-aging-memory-04","gap-immunology-aging-memory-05","gap-immunology-aging-memory-06","gap-immunology-aging-memory-07","gap-immunology-aging-memory-08","gap-immunology-aging-memory-09","gap-immunology-aging-memory-10","gap-immunology-aging-memory-11","gap-immunology-aging-memory-12"],"persona_reviews":[{"persona":"susan-kaech","verdict":"looks_right","supports":["cell_cd8_memory_aging","cell_metabolism_memory","cell_epigenetic_memory_reversal","cell_cmv_memory_inflation"],"rationale":"The map gives CD8 memory-state maintenance and rejuvenation their own cells instead of burying them inside generic immunosenescence, which matches the domain's core mechanistic split.","review_mode":"synthetic_from_domain_fit"},{"persona":"marion-pepper","verdict":"supportive","supports":["cell_trm_aging","cell_cd4_tfh_bcell_help","cell_vaccine_memory_older_adults","cell_bone_marrow_niches"],"rationale":"The partition respects tissue context and helper-memory biology, especially the distinction between blood-centered durability studies and niche-dependent memory maintenance.","review_mode":"synthetic_from_domain_fit"},{"persona":"claire-gustavson","verdict":"supportive","supports":["cell_allen_multiomic_atlas","cell_trained_immunity_inflammaging","cell_tissue_specific_atlas","cell_heterogeneity_sex_ancestry"],"rationale":"The landscape is correctly anchored on the Allen healthy-adult multi-omic atlas and keeps atlas coverage, heterogeneity, and innate-memory drift visible as separate frontier cells.","review_mode":"synthetic_from_domain_fit"}],"domain_description":"Immune-memory aging in humans, anchored on Allen Institute for Immunology programs. Covers adaptive and innate immune memory, age-linked tissue and niche effects, vaccination durability, and the neuroimmune boundary conditions most relevant to later-life inflammatory disease.","top_papers_by_cell":{"cell_trm_aging":[{"pmid":"37575227","year":2023,"title":"The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders.","journal":"Front Immunol"},{"pmid":"41156185","year":2025,"title":"From Tissue to Transcriptome: A Systematic Review of Multi-Level Evidence for Immune Dysregulation in Atrial Fibrillation.","journal":"J Clin Med"},{"pmid":"34220932","year":2021,"title":"Visual Genomics Analysis Studio as a Tool to Analyze Multiomic Data.","journal":"Front Genet"}],"cell_cd8_memory_aging":[{"pmid":"25385531","year":2014,"title":"Autophagy is a critical regulator of memory CD8(+) T cell formation.","journal":"Elife"},{"pmid":"25082296","year":2014,"title":"Uremia-associated immunological aging is stably imprinted in the T-cell system and not reversed by kidney transplantation.","journal":"Transpl Int"},{"pmid":"32260178","year":2020,"title":"Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses.","journal":"Toxins (Basel)"},{"pmid":"35528547","year":2022,"title":"Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching.","journal":"Nat Aging"}],"cell_metabolism_memory":[{"pmid":"34981777","year":2022,"title":"Targeting memory T cell metabolism to improve immunity.","journal":"J Clin Invest"},{"pmid":"39771976","year":2024,"title":"Immunosenescence: Aging and Immune System Decline.","journal":"Vaccines (Basel)"},{"pmid":"36201890","year":2022,"title":"IL-7: Comprehensive review.","journal":"Cytokine"},{"pmid":"31709535","year":2020,"title":"Skin barrier immunity and ageing.","journal":"Immunology"}],"cell_bone_marrow_niches":[{"pmid":"25014741","year":2014,"title":"The aging bone marrow and its impact on immune responses in old age.","journal":"Immunol Lett"},{"pmid":"35114061","year":2022,"title":"Dynamic organization of the bone marrow plasma cell niche.","journal":"FEBS J"},{"pmid":"18024073","year":2007,"title":"Impact of niche aging on thymic regeneration and immune reconstitution.","journal":"Semin Immunol"},{"pmid":"31018996","year":2019,"title":"The impact of oxidative stress, inflammation, and senescence on the maintenance of immunological memory in the bone marrow in old age.","journal":"Biosci Rep"}],"cell_cd4_tfh_bcell_help":[{"pmid":"24440384","year":2014,"title":"CD4 T cell defects in the aged: causes, consequences and strategies to circumvent.","journal":"Exp Gerontol"},{"pmid":"24217812","year":2014,"title":"How T follicular helper cells and the germinal centre response change with age.","journal":"Immunol Cell Biol"}],"cell_cmv_memory_inflation":[{"pmid":"31004198","year":2019,"title":"Impact of CMV upon immune aging: facts and fiction.","journal":"Med Microbiol Immunol"},{"pmid":"20727987","year":2011,"title":"Persistent viral infections and immune aging.","journal":"Ageing Res Rev"}],"cell_allen_multiomic_atlas":[],"cell_neuroimmune_interface":[{"pmid":"34364650","year":2022,"title":"Traumatic Brain Injury and Risk of Neurodegenerative Disorder.","journal":"Biol Psychiatry"},{"pmid":"33169684","year":2021,"title":"Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease.","journal":"Life Sci"},{"pmid":"38839924","year":2024,"title":"The path to next-generation disease-modifying immunomodulatory combination therapies in Alzheimer's disease.","journal":"Nat Aging"},{"pmid":"25199710","year":2014,"title":"Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: boosting autoimmunity to fight-off chronic neuroinflammation.","journal":"J Autoimmun"}],"cell_tissue_specific_atlas":[{"pmid":"31709535","year":2020,"title":"Skin barrier immunity and ageing.","journal":"Immunology"},{"pmid":"37741513","year":2023,"title":"Relevance of tissue-resident memory CD8 T cells in the onset of Parkinson's disease and examination of its possible etiologies: infectious or autoimmune?","journal":"Neurobiol Dis"},{"pmid":"40096943","year":2026,"title":"Intestinal tissue-resident memory T cells: Characteristics, spatial heterogeneity, age-related dynamics, and roles in disease regulation.","journal":"J Adv Res"},{"pmid":"33740452","year":2021,"title":"Tissue-specific immunity for a changing world.","journal":"Cell"}],"cell_human_intervention_trials":[{"pmid":"34342733","year":2021,"title":"Immune Checkpoint Inhibitors in the Aged.","journal":"Curr Oncol Rep"},{"pmid":"30006738","year":2019,"title":"Does patient age influence anti-cancer immunity?","journal":"Semin Immunopathol"},{"pmid":"28707274","year":2017,"title":"Cancer Immunotherapies: Are They as Effective in the Elderly?","journal":"Drugs Aging"},{"pmid":"40868058","year":2025,"title":"Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients.","journal":"Biomedicines"}],"cell_epigenetic_memory_reversal":[{"pmid":"41923646","year":2026,"title":"Memory T cell aging and rejuvenation.","journal":"Immunity"},{"pmid":"40987696","year":2025,"title":"CD8(+) T cell stressors converge on shared metabolic-epigenetic networks.","journal":"Trends Endocrinol Metab"}],"cell_heterogeneity_sex_ancestry":[{"pmid":"38967222","year":2024,"title":"Sex and gender differences in cognitive resilience to aging and Alzheimer's disease.","journal":"Alzheimers Dement"},{"pmid":"37967530","year":2023,"title":"Sex hormone signaling and regulation of immune function.","journal":"Immunity"},{"pmid":"39586033","year":2025,"title":"Sex, Gender, and COPD.","journal":"Annu Rev Physiol"},{"pmid":"34391943","year":2021,"title":"Immunosenescence and inflammaging in the aging process: age-related diseases or longevity?","journal":"Ageing Res Rev"}],"cell_vaccine_memory_older_adults":[{"pmid":"37662959","year":2023,"title":"Heterogeneity of memory T cells in aging.","journal":"Front Immunol"},{"pmid":"33190948","year":2020,"title":"Durability of humoral immune responses to rubella following MMR vaccination.","journal":"Vaccine"},{"pmid":"40386778","year":2025,"title":"Analysis of humoral and cellular immune activation up to 21 months after heterologous and homologous COVID-19 vaccination.","journal":"Front Immunol"},{"pmid":"40213554","year":2025,"title":"Longitudinal cellular and humoral immune responses following COVID-19 BNT162b2-mRNA-based booster vaccination of craft and manual workers in Qatar.","journal":"Front Immunol"}],"cell_trained_immunity_inflammaging":[{"pmid":"34536213","year":2023,"title":"Immunology of Aging: the Birth of Inflammaging.","journal":"Clin Rev Allergy Immunol"},{"pmid":"31055573","year":2019,"title":"Human Inflammaging.","journal":"Gerontology"},{"pmid":"40699053","year":2025,"title":"Metabolic dysregulation of trained immunity in immune aging and the impact of dietary patterns.","journal":"Am J Physiol Cell Physiol"},{"pmid":"32930852","year":2020,"title":"Immunosenescence is both functional/adaptive and dysfunctional/maladaptive.","journal":"Semin Immunopathol"}]},"frontier_commentary":"The Allen Immunology domain map for aging and immune memory is anchored by a recent multi-omic healthy-adult atlas, but most mechanistic cells remain frontier regions rather than settled territory. The mature core is the descriptive layer: blood-accessible age trajectories, CD8 memory-state remodeling, and the broad inflammaging vocabulary. What is still thin is the bridge from those descriptive states to durable, tissue-resolved causal mechanisms.\n\nTwo cells currently look comparatively mature (2 total): atlas-scale profiling and CD8 memory-state biology. A second tier of 5 cells has enough literature to support stable subfield labels but not enough convergence to collapse key disputes, especially around TRM maintenance, helper-memory failure, vaccine durability, and trained immunity.\n\nThe highest-value white space sits in 7 frontier cells where longitudinal intervention data, tissue sampling, and heterogeneity-aware study design are still sparse. Those gaps suggest the next SciDEX downstream work should emphasize cross-tissue atlas expansion, intervention-linked memory readouts, and neuroimmune-interface studies that explicitly connect peripheral memory compartments to age-associated CNS inflammation.","coverage_completeness":0.857,"landscape_analysis_row_id":2},"created_at":"2026-04-25T19:26:21.393166-07:00","updated_at":"2026-04-27T03:29:26.903750-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":"2026-04-25T19:26:21.393166-07:00","citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":"pass","contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"9e5dfff3-5889-4361-bd3e-4fdd722cb601","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"agent:cfecbef1-ea59-48a6-9531-1de8b2095ec7"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[],"incoming_links":[],"current_artifact_id":"landscape-immunology-aging-memory-v1","is_canonical":true,"supersede_chain":["landscape-immunology-aging-memory-v1"]}