{
  "asOf": "2026-09-15",
  "version": "Aging research map v1",
  "scope": "22 major research paths; targeted primary-source review, not an exhaustive systematic review",
  "missionProbability": null,
  "missionCost": null,
  "missionMarket": null,
  "forecast": "Uncalibrated analyst judgments conditional on usable data, staffing and the stated analysis budget. These are probabilities of the specified next research test, never probabilities of curing aging.",
  "assumptions": {
    "scientistRate": 100,
    "reviewRate": 150,
    "inputRate": 3,
    "outputRate": 15,
    "contingency": 20,
    "budgetRange": [
      0.65,
      1.6
    ],
    "marketPool": 3200,
    "marketBuyerMultipliers": [
      0.5,
      2
    ],
    "marketPriceMultipliers": [
      0.5,
      2
    ],
    "commercialProbability": null
  },
  "marketDefinition": "Illustrative annual US biotech R&D-tool market: assumed qualified buyers \u00d7 assumed annual contract price. Overlapping buyers; do not sum. No validated willingness to pay, revenue forecast or investor-return estimate.",
  "paths": [
    {
      "id": "transfer",
      "name": "Does an intervention transfer?",
      "group": "Evidence infrastructure",
      "evidenceLevel": "Executed data audit",
      "evidence": "Our DrugAge audit finds 23 compound names with mouse observations in at least two publications; 20 also cover both sexes. Publications do not establish independent replication.",
      "human": "The audit contains no human intervention outcomes and estimates no human efficacy.",
      "barrier": "Positive-literature selection, dependent controls, chemical aliases and study leakage can inflate apparent confidence.",
      "test": "Build a publication-linked intervention-outcome benchmark with a separately searched negative-study set and an untouched publication-date holdout.",
      "gate": "Adjudicate at least 150 independent experiment-control units with \u226595% source precision; a locked model reduces Brier score by \u226510% versus the strongest simple baseline on at least 50 unseen units, with a study-cluster bootstrap 95% interval excluding zero improvement.",
      "stop": "If independence or negative-study coverage cannot be established, publish a coverage dataset only. If calibration fails, stop prediction claims.",
      "sources": [
        "drugage",
        "drugage-paper",
        "itp",
        "prior-sex"
      ],
      "hours": 100,
      "review": 32,
      "compute": 250,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 30,
      "prange": [
        15,
        45
      ],
      "why": "The ingestion is working; independence and negative-study recovery are unresolved. This forecast is for the composite benchmark gate, not intervention efficacy.",
      "product": "Auditable preclinical evidence and replication planning",
      "buyers": 320,
      "price": 50000,
      "weeks": "4\u20136",
      "priority": "First test",
      "cost": 18324.0,
      "cash": 564.0,
      "tam": 16000000
    },
    {
      "id": "reprogramming",
      "name": "Partial cellular reprogramming",
      "group": "Repair cell state",
      "evidenceLevel": "Mouse function; human phase 1",
      "evidence": "OSK restored visual function in mouse experiments. This is organ-specific functional evidence, not whole-body lifespan reversal.",
      "human": "ER-100 is registered as recruiting phase 1 in optic neuropathies: estimated 18 participants, safety-focused primary outcomes, no posted results in the checked record. Last registry update: May 19, 2026.",
      "barrier": "Preserving cell identity, controlling delivery and excluding proliferative or cancer risk are central barriers. A younger clock can coexist with damaged function.",
      "test": "Reanalyze public reprogramming expression data across tissues; separate youthful-state recovery from loss of mature cell identity.",
      "gate": "On two untouched studies, improve prediction of independently measured functional recovery by \u226510% over age-only and cell-identity baselines, with a positive study-level uncertainty interval; identity-loss controls must be correctly flagged.",
      "stop": "If functional labels or two independent studies are unavailable, stop at dataset feasibility. Clock reversal alone cannot pass.",
      "sources": [
        "osk",
        "er100",
        "tage"
      ],
      "hours": 180,
      "review": 48,
      "compute": 900,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 20,
      "prange": [
        8,
        35
      ],
      "why": "Mechanistic and clinical activity support research interest; sparse matched function labels and strong existing models make this test difficult.",
      "product": "Reprogramming-response and identity-preservation assay analysis",
      "buyers": 480,
      "price": 75000,
      "weeks": "6\u20138",
      "priority": "High-upside test",
      "cost": 31584.0,
      "cash": 1344.0,
      "tam": 36000000
    },
    {
      "id": "senescence",
      "name": "Senescent-cell removal and control",
      "group": "Remove accumulated damage",
      "evidenceLevel": "Mouse survival; mixed human trial",
      "evidence": "Senolytic studies report improved function and survival in old mice; targeted CAR T approaches show durable metabolic effects in mice.",
      "human": "A 60-participant randomized bone study did not meet its primary resorption-marker endpoint. Baseline-burden subgroup signals were exploratory.",
      "barrier": "Senescence is heterogeneous and can help wound healing and tumor suppression. Marker abundance is not a universal target or response predictor.",
      "test": "Test whether baseline senescent-cell burden predicts measured response in public intervention datasets, withholding entire studies and tissue types.",
      "gate": "\u226510% lower response-prediction error than age plus cell-composition controls on two external studies, with a positive study-cluster interval and prospectively fixed burden markers.",
      "stop": "Stop if only post-treatment markers or exploratory human subgroups supply labels. No claim that all senescent cells should be eliminated.",
      "sources": [
        "sen-human",
        "sen-mouse",
        "sen-car"
      ],
      "hours": 140,
      "review": 40,
      "compute": 500,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 25,
      "prange": [
        10,
        40
      ],
      "why": "Biological effects exist, but target heterogeneity and small human studies limit transfer.",
      "product": "Senescence-response stratification for R&D",
      "buyers": 480,
      "price": 50000,
      "weeks": "5\u20137",
      "priority": "Exploratory",
      "cost": 24864.0,
      "cash": 864.0,
      "tam": 24000000
    },
    {
      "id": "mtor",
      "name": "Nutrient sensing and mTOR",
      "group": "Slow damage accumulation",
      "evidenceLevel": "Multisite mouse survival; human trial",
      "evidence": "Rapamycin is among the interventions with lifespan evidence in the NIA ITP, a three-site program using genetically heterogeneous mice.",
      "human": "PEARL reported no significant overall change in visceral adiposity, its registered primary endpoint; some secondary sex-specific outcomes changed. It did not test human lifespan.",
      "barrier": "Effects depend on context, and immune, metabolic and tolerability tradeoffs matter. Mouse survival cannot supply human odds.",
      "test": "Audit available ITP survival data with site, sex, censoring and shared-control structure preserved; test whether effects transfer to an unseen site or cohort.",
      "gate": "Reproduce published survival direction, then predict held-out site/sex effects with \u226510% lower error than the pooled intervention-only baseline and calibrated uncertainty.",
      "stop": "If unseen-site performance does not improve, retain a reproducibility report without a response-prediction claim.",
      "sources": [
        "itp",
        "itp-papers",
        "pearl",
        "pearl-reg"
      ],
      "hours": 100,
      "review": 32,
      "compute": 250,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 40,
      "prange": [
        20,
        60
      ],
      "why": "Replicated mouse data offer a relatively tractable analysis; predicting heterogeneity beyond pooled effects remains unproven.",
      "product": "Preclinical trial analysis and response modeling",
      "buyers": 320,
      "price": 40000,
      "weeks": "4\u20136",
      "priority": "Benchmark anchor",
      "cost": 18324.0,
      "cash": 564.0,
      "tam": 12800000
    },
    {
      "id": "diet",
      "name": "Dietary restriction and metabolic resilience",
      "group": "Slow damage accumulation",
      "evidenceLevel": "Mouse survival; human biomarkers",
      "evidence": "A large genetically diverse female-mouse study found lifespan benefits with substantial individual variation. Sex and genetic context limit generalization.",
      "human": "CALERIE methylation analysis found a small DunedinPACE change; different clocks did not agree uniformly. This is not evidence of added years of human life.",
      "barrier": "Weight loss, lower biological-age scores and resilience are different outcomes. Frailty, adherence and nutritional adequacy complicate translation.",
      "test": "Use the public diversity-outbred study to test baseline predictors of survival response, with all post-treatment information excluded from prediction.",
      "gate": "On untouched families or genotype groups, \u226510% lower integrated survival Brier score than age, baseline weight and diet assignment, with a positive clustered interval.",
      "stop": "No responder claim if individual treatment effects are inferred from observed survival alone or benefits disappear after baseline-only restriction.",
      "sources": [
        "diet-mouse",
        "calerie"
      ],
      "hours": 140,
      "review": 40,
      "compute": 450,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 30,
      "prange": [
        15,
        45
      ],
      "why": "Rich measurements help, but one female-only cohort cannot establish broad personalized efficacy.",
      "product": "Experimental resilience and nutrition-response analytics",
      "buyers": 320,
      "price": 30000,
      "weeks": "5\u20137",
      "priority": "Exploratory",
      "cost": 24804.0,
      "cash": 804.0,
      "tam": 9600000
    },
    {
      "id": "metabolic",
      "name": "Metabolic drug repurposing",
      "group": "Slow damage accumulation",
      "evidenceLevel": "Disease-specific human outcomes",
      "evidence": "Canagliflozin extended lifespan in male, but not female, ITP mice. The result illustrates why sex cannot be discarded during aggregation.",
      "human": "Empagliflozin reduced cardiovascular events and mortality in a high-risk type 2 diabetes trial. A disease-specific result is not general human aging reversal.",
      "barrier": "Indication, baseline disease and treatment selection create confounding; benefits in ill populations may not transfer to healthy adults.",
      "test": "Build an endpoint-aligned comparison of animal and human metabolic-intervention results, keeping randomized and observational evidence separate.",
      "gate": "\u226595% endpoint/population precision in a blinded 100-assertion audit, plus improved held-out trial-outcome classification over indication-only baseline with a positive study-level interval.",
      "stop": "If only observational comparisons support transfer, stop causal claims; a useful evidence table is a narrower outcome.",
      "sources": [
        "cana",
        "empa",
        "itp-papers"
      ],
      "hours": 120,
      "review": 36,
      "compute": 250,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 25,
      "prange": [
        10,
        40
      ],
      "why": "Human disease trials provide anchors, but cross-indication transfer is a much harder target.",
      "product": "Endpoint and indication evidence services",
      "buyers": 640,
      "price": 40000,
      "weeks": "4\u20136",
      "priority": "Exploratory",
      "cost": 21444.0,
      "cash": 564.0,
      "tam": 25600000
    },
    {
      "id": "autophagy",
      "name": "Autophagy, lysosomes and proteostasis",
      "group": "Remove accumulated damage",
      "evidenceLevel": "Genetic mouse lifespan experiment",
      "evidence": "A beclin-1 mutation that increased basal autophagy extended mouse lifespan and healthspan. Lifelong genetic change differs from late-life treatment.",
      "human": "The cited experiment establishes no human lifespan benefit from broadly increasing autophagy.",
      "barrier": "Protein clearance is tissue-dependent; static marker levels do not measure flux, and excessive recycling can damage cells.",
      "test": "Compare public perturbation datasets using functional clearance labels; test whether the model separates increased flux from blocked degradation.",
      "gate": "\u226510% lower error on externally measured clearance outcomes than expression-only pathway scores on two untouched studies, with a positive clustered interval.",
      "stop": "Stop if available labels are only marker abundance or if flux direction cannot be distinguished.",
      "sources": [
        "autophagy",
        "tage"
      ],
      "hours": 120,
      "review": 36,
      "compute": 400,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 25,
      "prange": [
        10,
        40
      ],
      "why": "The causal animal foothold is real; public functional-flux labels are the main feasibility risk.",
      "product": "Proteostasis assay interpretation",
      "buyers": 320,
      "price": 50000,
      "weeks": "4\u20136",
      "priority": "Exploratory",
      "cost": 21624.0,
      "cash": 744.0,
      "tam": 16000000
    },
    {
      "id": "mitochondria",
      "name": "Mitochondrial quality and mitophagy",
      "group": "Repair cell function",
      "evidenceLevel": "Human randomized biomarker studies",
      "evidence": "A 66-person urolithin A trial found secondary muscle-endurance signals, but no significant between-group benefit on its walk-distance or ATP primary endpoints.",
      "human": "A 2025 randomized 50-person study found immune-cell and metabolic changes over four weeks. It did not establish fewer infections or longer survival.",
      "barrier": "Improved mitochondrial markers may not restore meaningful function. Tissue context and baseline impairment affect response.",
      "test": "Test whether mitochondrial pathway changes predict functional improvement beyond baseline fitness and age in public intervention studies.",
      "gate": "\u226510% lower held-out functional-outcome error than baseline fitness plus age on two studies; primary and secondary endpoints remain separately scored.",
      "stop": "If only surrogate biomarkers are available, stop the functional prediction claim.",
      "sources": [
        "ua-muscle",
        "ua-immune"
      ],
      "hours": 120,
      "review": 36,
      "compute": 350,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 25,
      "prange": [
        10,
        40
      ],
      "why": "Human measurements exist, but discordant endpoints and limited open participant data constrain the test.",
      "product": "Mitochondrial response and assay analytics",
      "buyers": 320,
      "price": 40000,
      "weeks": "4\u20136",
      "priority": "Exploratory",
      "cost": 21564.0,
      "cash": 684.0,
      "tam": 12800000
    },
    {
      "id": "nad",
      "name": "NAD and cellular energy pathways",
      "group": "Repair cell function",
      "evidenceLevel": "Human target engagement; limited function",
      "evidence": "An NMN randomized study increased blood NAD-related metabolites, while its primary stepping test showed no between-group difference.",
      "human": "Biochemical target engagement is more established here than durable clinical benefit. Secondary walking and sleep results need independent confirmation.",
      "barrier": "Raising a metabolite is not proof that it is the limiting cause of decline; formulation, tissue uptake and endpoint choice differ.",
      "test": "Audit preregistered endpoints against published results across public NAD-precursor trials, with separate target-engagement and functional-outcome labels.",
      "gate": "\u226595% precision on a blinded 100-assertion endpoint audit and retrieval of at least 10 usable randomized comparisons; no missing primary outcome reclassified as success.",
      "stop": "Stop a response-prediction program if comparable function data are insufficient; publish the endpoint audit, including nulls.",
      "sources": [
        "nmn"
      ],
      "hours": 70,
      "review": 32,
      "compute": 150,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 45,
      "prange": [
        25,
        65
      ],
      "why": "This is an evidence-audit gate with limited biological inference, so it is more feasible than a therapeutic prediction.",
      "product": "Trial endpoint auditing for R&D teams",
      "buyers": 160,
      "price": 25000,
      "weeks": "3\u20134",
      "priority": "Exploratory",
      "cost": 14604.0,
      "cash": 444.0,
      "tam": 4000000
    },
    {
      "id": "genome",
      "name": "DNA maintenance and cancer restraint",
      "group": "Preserve information",
      "evidenceLevel": "Comparative mammalian evidence",
      "evidence": "Somatic mutation accumulation rates scale inversely with lifespan across studied mammals. This association motivates repair research without proving that changing one repair pathway extends human life.",
      "human": "No cited study demonstrates safe organism-wide genome repair that reverses human aging.",
      "barrier": "Repair fidelity, cancer surveillance, mosaic mutations and delivery across trillions of cells are coupled problems.",
      "test": "Reanalyze public comparative mutation and longevity data with phylogeny, tissue, body mass and study effects retained.",
      "gate": "A candidate mechanism improves held-out-clade lifespan-related prediction by \u226510% over body mass and phylogeny, with a positive clade-bootstrap interval and independent perturbation support.",
      "stop": "If the association collapses under clade holdout or relies on one tissue, stop general repair claims.",
      "sources": [
        "mutation"
      ],
      "hours": 180,
      "review": 48,
      "compute": 800,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 20,
      "prange": [
        8,
        35
      ],
      "why": "Comparative data offer leverage, but small species counts and confounding make causal transfer uncertain.",
      "product": "Comparative repair and target-evidence analysis",
      "buyers": 320,
      "price": 75000,
      "weeks": "6\u20138",
      "priority": "Exploratory",
      "cost": 31464.0,
      "cash": 1224.0,
      "tam": 24000000
    },
    {
      "id": "telomeres",
      "name": "Telomere maintenance",
      "group": "Preserve information",
      "evidenceLevel": "Mouse lifespan experiment",
      "evidence": "Telomerase gene therapy extended lifespan in an adult/old mouse experiment without increased cancer observed in that study.",
      "human": "That result does not establish cancer safety or longevity efficacy for generally healthy humans.",
      "barrier": "Telomere dysfunction and malignant growth are competing concerns; human and mouse telomere biology differ.",
      "test": "Integrate public telomere perturbation, damage and proliferation data to identify contexts where repair and proliferation signatures separate.",
      "gate": "Predict held-out functional rescue while discriminating proliferative-risk controls at prespecified \u226590% sensitivity across two independent datasets.",
      "stop": "Stop if the only success measure is longer telomeres or if functional rescue cannot be separated from proliferation.",
      "sources": [
        "tert",
        "mutation"
      ],
      "hours": 140,
      "review": 44,
      "compute": 500,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 20,
      "prange": [
        8,
        35
      ],
      "why": "The mouse result supports investigation; safety proxies are incomplete and functional labels scarce.",
      "product": "Telomere and proliferation-context analysis",
      "buyers": 160,
      "price": 60000,
      "weeks": "5\u20137",
      "priority": "Exploratory",
      "cost": 25584.0,
      "cash": 864.0,
      "tam": 9600000
    },
    {
      "id": "stem-cells",
      "name": "Stem-cell renewal and tissue regeneration",
      "group": "Replace damaged components",
      "evidenceLevel": "Mouse immune-function experiment",
      "evidence": "Depleting myeloid-biased stem cells in aged mice shifted immune production toward a younger pattern and improved immune responses.",
      "human": "This preclinical result does not establish systemic rejuvenation from commercial stem-cell treatments.",
      "barrier": "An aged niche, clonal expansion, engraftment and malignant potential can defeat otherwise youthful cells.",
      "test": "Use public single-cell aging atlases to predict functional lineage balance across donors, separating cell composition from within-cell changes.",
      "gate": "\u226510% lower donor-held-out lineage/function error than cell-composition and age baselines, plus external validation in a perturbation dataset.",
      "stop": "Stop if donor leakage or changing cell mixture accounts for the gain; a younger average expression profile is insufficient.",
      "sources": [
        "hsc",
        "immune-new"
      ],
      "hours": 160,
      "review": 44,
      "compute": 700,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 25,
      "prange": [
        10,
        40
      ],
      "why": "Cell-level public data are rich, but integration with functional lineage outcomes remains difficult.",
      "product": "Regenerative-cell and niche quality analysis",
      "buyers": 480,
      "price": 60000,
      "weeks": "5\u20137",
      "priority": "Exploratory",
      "cost": 28224.0,
      "cash": 1104.0,
      "tam": 28800000
    },
    {
      "id": "immunity",
      "name": "Immune renewal and chronic inflammation",
      "group": "Coordinate repair",
      "evidenceLevel": "Mouse survival; human associations",
      "evidence": "IL-11 inhibition extended mouse lifespan in a published study. A newer mRNA study restored immune cues and improved aged-mouse vaccine and antitumor responses.",
      "human": "A 2026 thymic-imaging study links thymic health to human outcomes in two cohorts; it is observational, not proof that altering the thymus improves survival.",
      "barrier": "Suppressing inflammation can impair host defense. Immune rejuvenation must preserve infection control and self-tolerance.",
      "test": "Test a tissue-aware immune-resilience signature against held-out functional challenge outcomes, retaining infection and inflammatory responses separately.",
      "gate": "\u226510% lower external-study error than age and immune-cell counts for functional response, with no degradation in prespecified host-defense risk classification.",
      "stop": "Stop if the signal predicts inflammation markers only or cannot distinguish protection from immune suppression.",
      "sources": [
        "il11",
        "immune-new",
        "thymus",
        "hsc"
      ],
      "hours": 160,
      "review": 48,
      "compute": 600,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 30,
      "prange": [
        15,
        45
      ],
      "why": "Functional perturbation studies create a useful target; human causal validation is still missing.",
      "product": "Immune-resilience and trial-stratification analytics",
      "buyers": 480,
      "price": 60000,
      "weeks": "5\u20137",
      "priority": "Priority after benchmark",
      "cost": 28824.0,
      "cash": 984.0,
      "tam": 28800000
    },
    {
      "id": "matrix",
      "name": "Extracellular matrix, fibrosis and crosslinks",
      "group": "Remove accumulated damage",
      "evidenceLevel": "Transferred gene: mouse function and survival",
      "evidence": "Expression of naked mole-rat Has2 in mice increased hyaluronan, improved health measures and extended lifespan. This is one transferable-mechanism example.",
      "human": "The cited work does not demonstrate a human crosslink-removal or whole-body matrix-rejuvenation treatment.",
      "barrier": "Matrix damage differs by organ. Removing scar or crosslinks without preserving tissue strength requires functional validation.",
      "test": "Compare aging and anti-fibrotic perturbation datasets using matrix mechanics or organ-function labels where available.",
      "gate": "\u226510% lower held-out functional/mechanical outcome error than fibrosis-marker expression alone on two independent studies.",
      "stop": "If only transcript levels are available, stop claims about restored tissue mechanics.",
      "sources": [
        "has2",
        "tage"
      ],
      "hours": 120,
      "review": 40,
      "compute": 400,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 20,
      "prange": [
        8,
        35
      ],
      "why": "Cross-species transfer is demonstrated for one mechanism, but the relevant public mechanical measurements are sparse.",
      "product": "Matrix and fibrosis response analysis",
      "buyers": 320,
      "price": 50000,
      "weeks": "4\u20136",
      "priority": "Exploratory",
      "cost": 22344.0,
      "cash": 744.0,
      "tam": 16000000
    },
    {
      "id": "systemic",
      "name": "Circulating and endocrine signals",
      "group": "Coordinate repair",
      "evidenceLevel": "Mouse multi-tissue and survival evidence",
      "evidence": "Prolonged heterochronic parabiosis produced sustained molecular changes and extended survival in old mice in a published study.",
      "human": "This does not establish a benefit from human young-plasma products, because shared circulation includes many physiological changes beyond added factors.",
      "barrier": "Young factors, removal of harmful factors, shared organ function and surgery effects must be separated.",
      "test": "Reanalyze public single-cell parabiosis data and independent factor-perturbation studies to test mechanism-specific transfer.",
      "gate": "A frozen signature predicts an independent measured functional outcome beyond cell composition and generic injury response in two held-out studies.",
      "stop": "Stop if surgery, tissue mix or age labels explain the prediction; parabiosis results cannot be equated to plasma infusion.",
      "sources": [
        "plasma",
        "plasma-sc"
      ],
      "hours": 140,
      "review": 40,
      "compute": 650,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 20,
      "prange": [
        8,
        35
      ],
      "why": "Rich expression data are available; causal attribution to individual circulating signals remains a major gap.",
      "product": "Systemic signaling and response-evidence services",
      "buyers": 320,
      "price": 50000,
      "weeks": "5\u20137",
      "priority": "Exploratory",
      "cost": 25044.0,
      "cash": 1044.0,
      "tam": 16000000
    },
    {
      "id": "microbiome",
      "name": "Microbiome and host interactions",
      "group": "Coordinate repair",
      "evidenceLevel": "Mouse cognition and immune effects",
      "evidence": "Young-donor microbiota altered immune/metabolic features and improved selected behavioral outcomes in aged mice.",
      "human": "The cited study supplies no evidence that microbiota transfer reverses general human aging.",
      "barrier": "Diet, drugs, geography, cages and donor-recipient compatibility strongly affect composition and function.",
      "test": "Test whether microbial functional pathways transfer across aging cohorts more reliably than taxonomic abundance, with cohort and host covariates withheld.",
      "gate": "\u226510% lower external-cohort functional-outcome error than diet, age and taxonomy baselines across at least two independent cohorts.",
      "stop": "Stop if the model identifies cohort, cage or diet rather than function; no causal claim from cross-sectional composition.",
      "sources": [
        "microbiome"
      ],
      "hours": 120,
      "review": 36,
      "compute": 450,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 20,
      "prange": [
        8,
        35
      ],
      "why": "Data volume is large but functional endpoints and confounder control are inconsistent.",
      "product": "Host-microbiome functional evidence analysis",
      "buyers": 320,
      "price": 35000,
      "weeks": "4\u20136",
      "priority": "Exploratory",
      "cost": 21684.0,
      "cash": 804.0,
      "tam": 11200000
    },
    {
      "id": "organs",
      "name": "Organ replacement and preservation",
      "group": "Replace damaged components",
      "evidenceLevel": "Human case report; animal preservation",
      "evidence": "A gene-edited porcine kidney supported a living human recipient in a reported case. Rat kidney vitrification and nanowarming enabled life-sustaining transplantation.",
      "human": "These are organ-specific advances with major immunological and durability constraints; a single case is not a general survival estimate.",
      "barrier": "Organ supply, vascular integration, rejection, infection and preservation damage remain bottlenecks; replacing peripheral organs does not preserve brain function.",
      "test": "Build an outcome-linked preservation and transplant evidence dataset with organ, species, preservation time and follow-up explicitly separated.",
      "gate": "\u226595% audited endpoint precision and \u226510% lower held-out-study prediction error for prespecified graft function than preservation-time/species controls.",
      "stop": "If compatible outcome definitions or independent cohorts are insufficient, stop predictive claims and retain the evidence resource.",
      "sources": [
        "kidney",
        "cryo"
      ],
      "hours": 140,
      "review": 48,
      "compute": 400,
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      "outputM": 4,
      "p": 20,
      "prange": [
        8,
        35
      ],
      "why": "Tangible function is measurable, but public samples are small and protocols differ substantially.",
      "product": "Organ preservation and graft-evidence analytics",
      "buyers": 160,
      "price": 75000,
      "weeks": "5\u20137",
      "priority": "Exploratory",
      "cost": 26184.0,
      "cash": 744.0,
      "tam": 12000000
    },
    {
      "id": "brain",
      "name": "Brain and neurovascular preservation",
      "group": "Preserve function and identity",
      "evidenceLevel": "Disease-specific human trial; mouse function",
      "evidence": "Young CSF/FGF17 experiments improved memory-related outcomes in aged mice. Lecanemab slowed decline in early Alzheimer disease rather than restoring a youthful brain.",
      "human": "The Alzheimer trial provides disease-specific clinical evidence with adverse-event tradeoffs; it does not establish broad cognitive rejuvenation.",
      "barrier": "Memory, circuitry, vascular integrity and protein pathology can fail separately. Peripheral rejuvenation cannot substitute for durable cognition.",
      "test": "Test whether pathway-specific molecular changes predict independent cognitive or neuronal-function outcomes beyond age and disease severity.",
      "gate": "\u226510% lower donor/study-held-out functional error than age, disease stage and generic inflammation baselines, with a positive external-study interval.",
      "stop": "Stop if only molecular-age changes are available or the model predicts disease diagnosis rather than functional recovery.",
      "sources": [
        "csf",
        "lecanemab"
      ],
      "hours": 180,
      "review": 48,
      "compute": 900,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 15,
      "prange": [
        5,
        30
      ],
      "why": "Functional translation is unusually hard and open longitudinal brain data are limited.",
      "product": "Neurodegeneration target and outcome evidence",
      "buyers": 480,
      "price": 75000,
      "weeks": "6\u20138",
      "priority": "Exploratory",
      "cost": 31584.0,
      "cash": 1344.0,
      "tam": 36000000
    },
    {
      "id": "comparative",
      "name": "Comparative longevity genomics",
      "group": "Discover transferable mechanisms",
      "evidenceLevel": "Cross-species association plus perturbation example",
      "evidence": "Mammalian mutation-rate patterns and the Has2 transfer experiment support studying unusually long-lived species. They do not imply one universal longevity gene.",
      "human": "Human benefit from a comparative target requires tissue-specific functional and safety validation.",
      "barrier": "Ancestry, body size, cancer adaptation, sampling and tissue state confound naive genome-to-lifespan correlations.",
      "test": "Extend DNALYZER\u2019s genome\u2013phenome approach with longevity, repair, cell-state and perturbation evidence; withhold entire clades.",
      "gate": "An unpublished mechanism survives phylogenetic controls, improves held-out-clade prediction \u226510% over body-mass/ancestry baselines, and has independent functional support.",
      "stop": "Stop if no genuinely independent transitions or clades remain, or if known-target recovery is mistaken for novelty.",
      "sources": [
        "mutation",
        "has2",
        "tage"
      ],
      "hours": 180,
      "review": 48,
      "compute": 850,
      "other": 100,
      "inputM": 20,
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      "p": 20,
      "prange": [
        8,
        35
      ],
      "why": "The strategy fits DNALYZER, but prior anatomy failures and strong comparative confounding lower the initial prior.",
      "product": "Comparative longevity target-evidence platform",
      "buyers": 480,
      "price": 75000,
      "weeks": "6\u20138",
      "priority": "High-upside test",
      "cost": 31524.0,
      "cash": 1284.0,
      "tam": 36000000
    },
    {
      "id": "clocks",
      "name": "Aging measurements that predict outcomes",
      "group": "Evidence infrastructure",
      "evidenceLevel": "Human associations; intervention-response models",
      "evidence": "2026 tAge work integrates over 11,000 transcriptomes across four mammals and predicts multiple aging and mortality-related outcomes. It is substantial prior art.",
      "human": "A biomarker associated with mortality is not automatically a validated surrogate for treatment-induced survival benefit. CALERIE also illustrates clock disagreement.",
      "barrier": "Training contamination, cell mixture, regression to the mean and optimizing the measured clock can manufacture apparent rejuvenation.",
      "test": "Benchmark fixed published models on study- and intervention-held-out data, scoring functional outcomes rather than chronological-age accuracy alone.",
      "gate": "\u226510% lower held-out functional/mortality prediction error than the strongest licensed applicable published model, calibrated intervals, and documented training-data overlap audit.",
      "stop": "Stop a new-model claim if it cannot beat existing models or if licensed weights/data cannot be used in the intended setting.",
      "sources": [
        "tage",
        "calerie",
        "network"
      ],
      "hours": 160,
      "review": 44,
      "compute": 900,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 25,
      "prange": [
        10,
        40
      ],
      "why": "Open tools reduce implementation cost; current strong baselines reduce the odds of meaningful incremental gain.",
      "product": "Independent biomarker validation and trial analytics",
      "buyers": 640,
      "price": 40000,
      "weeks": "5\u20137",
      "priority": "Priority after benchmark",
      "cost": 28464.0,
      "cash": 1344.0,
      "tam": 25600000
    },
    {
      "id": "combinations",
      "name": "Combinations and sequential repair",
      "group": "Integrate interventions",
      "evidenceLevel": "Mouse lifespan combination study",
      "evidence": "A 2025 study found combined rapamycin and trametinib extended mouse survival more than either alone. Some control/single-treatment survival curves had been published earlier.",
      "human": "The study establishes neither human combination safety nor indefinite lifespan extension.",
      "barrier": "Overlapping mechanisms, toxicity, antagonism and shared controls invalidate simple addition of individual benefits.",
      "test": "Audit public combination studies against matched single-agent arms; test interaction prediction with entire combinations withheld.",
      "gate": "For at least 10 independent factorial experiment units, predict held-out interaction direction better than an additive baseline with a positive study-level interval.",
      "stop": "Stop if compatible factorial data are too sparse or reused controls are counted as independent evidence. Do not add claimed years of life.",
      "sources": [
        "combo",
        "itp-papers"
      ],
      "hours": 140,
      "review": 44,
      "compute": 650,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 15,
      "prange": [
        5,
        30
      ],
      "why": "Combination benefits provide a foothold, but comparable factorial data are scarce and interaction prediction is difficult.",
      "product": "Combination experiment design and evidence analysis",
      "buyers": 320,
      "price": 60000,
      "weeks": "5\u20137",
      "priority": "Exploratory",
      "cost": 25764.0,
      "cash": 1044.0,
      "tam": 19200000
    },
    {
      "id": "prevention",
      "name": "Proven function-preserving comparators",
      "group": "Human outcome benchmark",
      "evidenceLevel": "Randomized human functional outcomes",
      "evidence": "The LIFE randomized trial found that structured physical activity reduced major mobility disability in sedentary older adults at risk.",
      "human": "This is direct human functional evidence. It does not demonstrate reversal of every aging process or unlimited lifespan.",
      "barrier": "Experimental aging programs must show incremental value over useful existing care and function-preserving approaches.",
      "test": "Create an endpoint-aligned benchmark comparing experimental claims with randomized human functional-outcome evidence.",
      "gate": "\u226595% source/endpoint precision in 100 blinded assertions and zero substitution of biomarker change for clinical benefit in the final adjudicated benchmark.",
      "stop": "Stop comparisons across incompatible populations or endpoints; avoid treating an aging-score shift as equivalent to preserved mobility.",
      "sources": [
        "life",
        "empa",
        "lecanemab"
      ],
      "hours": 60,
      "review": 28,
      "compute": 100,
      "other": 100,
      "inputM": 20,
      "outputM": 4,
      "p": 50,
      "prange": [
        30,
        70
      ],
      "why": "This is a bounded evidence-quality task with established sources, not a forecast that a new treatment works.",
      "product": "Clinical endpoint comparators for research teams",
      "buyers": 160,
      "price": 25000,
      "weeks": "2\u20134",
      "priority": "Exploratory",
      "cost": 12624.0,
      "cash": 384.0,
      "tam": 4000000
    }
  ],
  "sources": [
    {
      "id": "hallmarks",
      "title": "Twelve hallmarks: a research taxonomy",
      "url": "https://doi.org/10.1016/j.cell.2022.11.001",
      "kind": "Review / taxonomy",
      "year": 2023,
      "checked": "2026-09-15"
    },
    {
      "id": "drugage",
      "title": "DrugAge bulk release and documentation",
      "url": "https://www.genomics.senescence.info/download.html",
      "kind": "Public dataset",
      "year": 2024,
      "checked": "2026-09-15"
    },
    {
      "id": "drugage-paper",
      "title": "DrugAge database publication",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5418190/",
      "kind": "Data resource paper",
      "year": 2017,
      "checked": "2026-09-15"
    },
    {
      "id": "hagr-license",
      "title": "HAGR attribution and reuse terms",
      "url": "https://www.genomics.senescence.info/legal.html",
      "kind": "Provider terms",
      "year": 2026,
      "checked": "2026-09-15"
    },
    {
      "id": "itp",
      "title": "NIA Interventions Testing Program",
      "url": "https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/about-itp",
      "kind": "Research program / data",
      "year": 2026,
      "checked": "2026-09-15"
    },
    {
      "id": "itp-papers",
      "title": "ITP positive and negative publications",
      "url": "https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/publications",
      "kind": "Primary publication index",
      "year": 2026,
      "checked": "2026-09-15"
    },
    {
      "id": "pearl",
      "title": "PEARL: human rapamycin trial results",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40188830/",
      "kind": "Primary study",
      "year": 2025,
      "checked": "2026-09-15"
    },
    {
      "id": "pearl-reg",
      "title": "PEARL registered outcomes",
      "url": "https://clinicaltrials.gov/study/NCT04488601",
      "kind": "Trial registry",
      "year": 2024,
      "checked": "2026-09-15"
    },
    {
      "id": "osk",
      "title": "Reprogramming and restored vision in mice",
      "url": "https://www.nature.com/articles/s41586-020-2975-4",
      "kind": "Primary study",
      "year": 2020,
      "checked": "2026-09-15"
    },
    {
      "id": "er100",
      "title": "ER-100 phase 1 optic-neuropathy trial",
      "url": "https://clinicaltrials.gov/study/NCT07290244",
      "kind": "Trial registry",
      "year": 2026,
      "checked": "2026-09-15"
    },
    {
      "id": "sen-human",
      "title": "Senolytics: randomized bone-metabolism trial",
      "url": "https://www.nature.com/articles/s41591-024-03096-2",
      "kind": "Primary study",
      "year": 2024,
      "checked": "2026-09-15"
    },
    {
      "id": "sen-mouse",
      "title": "Senolytics: function and survival in old mice",
      "url": "https://www.nature.com/articles/s41591-018-0092-9",
      "kind": "Primary study",
      "year": 2018,
      "checked": "2026-09-15"
    },
    {
      "id": "sen-car",
      "title": "Senolytic CAR T cells in mice",
      "url": "https://www.nature.com/articles/s43587-023-00560-5",
      "kind": "Primary study",
      "year": 2024,
      "checked": "2026-09-15"
    },
    {
      "id": "diet-mouse",
      "title": "Dietary restriction in genetically diverse female mice",
      "url": "https://www.nature.com/articles/s41586-024-08026-3",
      "kind": "Primary study",
      "year": 2024,
      "checked": "2026-09-15"
    },
    {
      "id": "calerie",
      "title": "CALERIE randomized-trial methylation analysis",
      "url": "https://www.nature.com/articles/s43587-022-00357-y",
      "kind": "Primary study",
      "year": 2023,
      "checked": "2026-09-15"
    },
    {
      "id": "cana",
      "title": "Canagliflozin: sex-dependent mouse survival",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7710304/",
      "kind": "Primary study",
      "year": 2020,
      "checked": "2026-09-15"
    },
    {
      "id": "empa",
      "title": "Empagliflozin: cardiovascular outcomes in diabetes",
      "url": "https://www.nejm.org/doi/full/10.1056/NEJMoa1504720",
      "kind": "Primary study",
      "year": 2015,
      "checked": "2026-09-15"
    },
    {
      "id": "autophagy",
      "title": "Beclin-1 autophagy and mouse longevity",
      "url": "https://www.nature.com/articles/s41586-018-0162-7",
      "kind": "Primary study",
      "year": 2018,
      "checked": "2026-09-15"
    },
    {
      "id": "ua-muscle",
      "title": "Urolithin A: randomized muscle-function trial",
      "url": "https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788244",
      "kind": "Primary study",
      "year": 2022,
      "checked": "2026-09-15"
    },
    {
      "id": "ua-immune",
      "title": "Urolithin A: randomized immune-biomarker trial",
      "url": "https://www.nature.com/articles/s43587-025-00996-x",
      "kind": "Primary study",
      "year": 2025,
      "checked": "2026-09-15"
    },
    {
      "id": "nmn",
      "title": "NMN: randomized function and NAD trial",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11336149/",
      "kind": "Primary study",
      "year": 2024,
      "checked": "2026-09-15"
    },
    {
      "id": "mutation",
      "title": "Somatic mutations across mammalian lifespans",
      "url": "https://www.nature.com/articles/s41586-022-04618-z",
      "kind": "Primary study",
      "year": 2022,
      "checked": "2026-09-15"
    },
    {
      "id": "tert",
      "title": "Telomerase gene therapy in adult and old mice",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3494070/",
      "kind": "Primary study",
      "year": 2012,
      "checked": "2026-09-15"
    },
    {
      "id": "hsc",
      "title": "Depletion of biased stem cells in aged mice",
      "url": "https://www.nature.com/articles/s41586-024-07238-x",
      "kind": "Primary study",
      "year": 2024,
      "checked": "2026-09-15"
    },
    {
      "id": "il11",
      "title": "IL-11 inhibition and mouse survival",
      "url": "https://www.nature.com/articles/s41586-024-07701-9",
      "kind": "Primary study",
      "year": 2024,
      "checked": "2026-09-15"
    },
    {
      "id": "immune-new",
      "title": "Transient restoration of immune cues in aged mice",
      "url": "https://www.nature.com/articles/s41586-025-09873-4",
      "kind": "Primary study",
      "year": 2025,
      "checked": "2026-09-15"
    },
    {
      "id": "thymus",
      "title": "Thymic imaging and human health outcomes",
      "url": "https://www.nature.com/articles/s41586-026-10242-y",
      "kind": "Primary study",
      "year": 2026,
      "checked": "2026-09-15"
    },
    {
      "id": "has2",
      "title": "Naked mole-rat Has2 transferred to mice",
      "url": "https://www.nature.com/articles/s41586-023-06463-0",
      "kind": "Primary study",
      "year": 2023,
      "checked": "2026-09-15"
    },
    {
      "id": "plasma",
      "title": "Youthful circulation and mouse lifespan",
      "url": "https://www.nature.com/articles/s43587-023-00451-9",
      "kind": "Primary study",
      "year": 2023,
      "checked": "2026-09-15"
    },
    {
      "id": "plasma-sc",
      "title": "Parabiosis at single-cell resolution",
      "url": "https://www.nature.com/articles/s41586-022-04461-2",
      "kind": "Primary study",
      "year": 2022,
      "checked": "2026-09-15"
    },
    {
      "id": "microbiome",
      "title": "Young microbiota and cognition in aged mice",
      "url": "https://www.nature.com/articles/s43587-021-00093-9",
      "kind": "Primary study",
      "year": 2021,
      "checked": "2026-09-15"
    },
    {
      "id": "kidney",
      "title": "Porcine kidney transplantation in a living recipient",
      "url": "https://www.nejm.org/doi/10.1056/NEJMoa2412747",
      "kind": "Primary study",
      "year": 2025,
      "checked": "2026-09-15"
    },
    {
      "id": "cryo",
      "title": "Rat kidney cryopreservation and transplantation",
      "url": "https://www.nature.com/articles/s41467-023-38824-8",
      "kind": "Primary study",
      "year": 2023,
      "checked": "2026-09-15"
    },
    {
      "id": "csf",
      "title": "Young CSF and memory in aged mice",
      "url": "https://www.nature.com/articles/s41586-022-04722-0",
      "kind": "Primary study",
      "year": 2022,
      "checked": "2026-09-15"
    },
    {
      "id": "lecanemab",
      "title": "Lecanemab in early Alzheimer disease",
      "url": "https://www.nejm.org/doi/full/10.1056/NEJMoa2212948",
      "kind": "Primary study",
      "year": 2023,
      "checked": "2026-09-15"
    },
    {
      "id": "tage",
      "title": "Cross-species transcriptomic aging and mortality models",
      "url": "https://www.nature.com/articles/s41586-026-10542-3",
      "kind": "Primary study",
      "year": 2026,
      "checked": "2026-09-15"
    },
    {
      "id": "combo",
      "title": "Rapamycin plus trametinib in mice",
      "url": "https://www.nature.com/articles/s43587-025-00876-4",
      "kind": "Primary study",
      "year": 2025,
      "checked": "2026-09-15"
    },
    {
      "id": "life",
      "title": "LIFE: randomized physical-activity and mobility trial",
      "url": "https://jamanetwork.com/journals/jama/fullarticle/1875328",
      "kind": "Primary study",
      "year": 2014,
      "checked": "2026-09-15"
    },
    {
      "id": "network",
      "title": "Network-based aging drug prioritization",
      "url": "https://www.nature.com/articles/s43587-026-01161-8",
      "kind": "Primary study",
      "year": 2026,
      "checked": "2026-09-15"
    },
    {
      "id": "prior-sex",
      "title": "Prior DrugAge sex-specific mouse analysis",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12089533/",
      "kind": "Primary study",
      "year": 2025,
      "checked": "2026-09-15"
    },
    {
      "id": "market",
      "title": "NSF biotechnology R&D company reference pool",
      "url": "https://ncses.nsf.gov/pubs/nsf25354/assets/data-tables/tables/nsf25354-tab019.pdf",
      "kind": "Market denominator",
      "year": 2025,
      "checked": "2026-09-15"
    },
    {
      "id": "labor",
      "title": "BLS medical scientist wage context",
      "url": "https://www.bls.gov/ooh/life-physical-and-social-science/medical-scientists.htm",
      "kind": "Labor-cost context",
      "year": 2026,
      "checked": "2026-09-15"
    }
  ]
}