{
  "checked": "2026-11-01",
  "records": [
    {
      "id": "tert",
      "name": "TERT / TERC — telomere maintenance",
      "type": "gene",
      "evidence": "animal",
      "genes": [
        "TERT",
        "TERC"
      ],
      "pathway": "Preserve · telomeres",
      "summary": "Telomere maintenance is a repair target with a cancer tradeoff, rather than a universal anti-aging switch.",
      "species": "Adult and old mice; separate human genetic-risk study",
      "outcome": "Mouse telomerase gene therapy improved several health measures and increased survival in the studied cohorts.",
      "limitations": "No human lifespan-extension result. Mouse telomere biology and study follow-up limit translation.",
      "risks": "Human genetic analyses link longer inherited telomeres to increased risk of several cancers.",
      "nextMilestone": "Demonstrate tissue-specific benefit with durable cancer surveillance in human trials.",
      "sourceIds": [
        "telomere-mouse",
        "telomere-cancer"
      ]
    },
    {
      "id": "tp53",
      "name": "TP53 — preserve regulated cancer surveillance",
      "type": "gene",
      "evidence": "animal",
      "genes": [
        "TP53"
      ],
      "pathway": "Protect · DNA-damage checkpoint",
      "summary": "Cancer control and regeneration need coordinated regulation. Simply disabling a checkpoint is a poor research shortcut.",
      "species": "Genetically modified mice",
      "outcome": "Extra normally regulated p53 copies improved cancer resistance without the premature-aging phenotype seen in other p53 models.",
      "limitations": "This is a mouse genetic model, not a validated human regenerative therapy.",
      "risks": "Overactive or lost checkpoint function can each be problematic; regulation and tissue context matter.",
      "nextMilestone": "Test whether regenerative benefit can coexist with controlled checkpoint responses.",
      "sourceIds": [
        "p53"
      ]
    },
    {
      "id": "foxo3",
      "name": "FOXO3 — human longevity association",
      "type": "gene",
      "evidence": "human-association",
      "genes": [
        "FOXO3"
      ],
      "pathway": "Preserve · stress-response regulation",
      "summary": "Inherited variation near FOXO3 has been associated with exceptional survival. It identifies a research pathway, not an editing prescription.",
      "species": "Human nested case-control study of Japanese-American men",
      "outcome": "Longevity-associated genotypes were enriched among long-lived participants.",
      "limitations": "Association does not show that increasing FOXO3 in adults extends life; population and variant context matter.",
      "risks": "Broad transcription-factor manipulation has uncertain effects across tissues.",
      "nextMilestone": "Identify causal variants and establish safe tissue-specific therapeutic effects.",
      "sourceIds": [
        "foxo3"
      ]
    },
    {
      "id": "apoe",
      "name": "APOE — longevity and disease-risk context",
      "type": "gene",
      "evidence": "human-association",
      "genes": [
        "APOE"
      ],
      "pathway": "Preserve · lipid transport / disease risk",
      "summary": "Human longevity genetics connects disease susceptibility with survival. APOE alleles are context-dependent risk markers.",
      "species": "Human longevity GWAS meta-analysis",
      "outcome": "APOE ε4 was associated with lower odds and ε2 with higher odds of reaching extreme survival percentiles.",
      "limitations": "Population odds do not predict an individual lifespan or demonstrate a gene-editing benefit.",
      "risks": "A change intended to modify one disease risk can affect other functions.",
      "nextMilestone": "Demonstrate disease-specific benefit and long-term safety of any intervention.",
      "sourceIds": [
        "apoe"
      ]
    },
    {
      "id": "igf1r",
      "name": "IGF1R — growth versus maintenance",
      "type": "gene",
      "evidence": "human-association",
      "genes": [
        "IGF1",
        "IGF1R"
      ],
      "pathway": "Preserve · growth signaling",
      "summary": "Reduced receptor activity associated with rare centenarian variants motivates research on growth-maintenance balance.",
      "species": "Human centenarian genetics and cellular receptor assays",
      "outcome": "Some heterozygous IGF1R mutations were enriched in female centenarians and showed reduced receptor activity.",
      "limitations": "Lifelong inherited variation is not equivalent to switching the pathway off in an older adult.",
      "risks": "Growth signaling also supports tissue maintenance and repair.",
      "nextMilestone": "Resolve when, where and how pathway modulation could help without impairing function.",
      "sourceIds": [
        "igf"
      ]
    },
    {
      "id": "ghr",
      "name": "GHR — low growth signaling and disease burden",
      "type": "gene",
      "evidence": "human-association",
      "genes": [
        "GHR",
        "IGF1"
      ],
      "pathway": "Preserve · endocrine growth signaling",
      "summary": "A rare inherited GHR-deficiency cohort offers evidence about cancer and metabolic disease, with important developmental differences.",
      "species": "Ecuadorian human GHR-deficiency cohort",
      "outcome": "The study observed markedly lower cancer and diabetes occurrence in this specific cohort.",
      "limitations": "Observational inherited-disease evidence does not establish that adult GHR suppression produces exceptional lifespan.",
      "risks": "Endocrine, developmental and metabolic effects complicate translation.",
      "nextMilestone": "Separate beneficial signaling changes from developmental and tissue-maintenance costs.",
      "sourceIds": [
        "ghr"
      ]
    },
    {
      "id": "sirt6",
      "name": "SIRT6 — energy homeostasis and maintenance",
      "type": "gene",
      "evidence": "animal",
      "genes": [
        "SIRT6"
      ],
      "pathway": "Repair · metabolic coordination",
      "summary": "SIRT6 is a candidate for maintaining metabolic function rather than simply promoting cell division.",
      "species": "Transgenic B6 mice, both sexes",
      "outcome": "Overexpression reduced frailty and extended lifespan with altered energy homeostasis.",
      "limitations": "No demonstrated human lifespan therapy; transgenic expression is not ordinary supplementation.",
      "risks": "Multi-tissue metabolic regulation may produce context-dependent effects.",
      "nextMilestone": "Replicate translational benefit with controlled intervention and long-term safety.",
      "sourceIds": [
        "sirt6"
      ]
    },
    {
      "id": "atg5",
      "name": "ATG5 — cellular recycling capacity",
      "type": "gene",
      "evidence": "animal",
      "genes": [
        "ATG5"
      ],
      "pathway": "Repair · autophagy",
      "summary": "Autophagy removes cellular material through recycling pathways; boosting it is a maintenance hypothesis with mouse evidence.",
      "species": "Transgenic mice",
      "outcome": "Atg5 overexpression increased autophagic activity and extended survival in the studied lines.",
      "limitations": "No validated human ATG5 longevity treatment; altered expression from early life differs from late-life therapy.",
      "risks": "More recycling is not automatically better in every cell or disease context.",
      "nextMilestone": "Show controlled restoration of impaired quality control in human tissues.",
      "sourceIds": [
        "atg5"
      ]
    },
    {
      "id": "mtor",
      "name": "MTOR — modulate growth and repair balance",
      "type": "gene",
      "evidence": "animal",
      "genes": [
        "MTOR"
      ],
      "pathway": "Preserve · nutrient sensing",
      "summary": "The mTOR pathway is a major geroscience target. Pharmacologic pathway evidence should not be read as support for deleting the gene.",
      "species": "Genetically heterogeneous mice at three sites",
      "outcome": "Late-life rapamycin extended median and maximal mouse lifespan in the study.",
      "limitations": "This primary study supplies mouse survival evidence, not human survival benefit or a gene-knockout result.",
      "risks": "Growth, immunity and healing require an appropriate balance of pathway activity.",
      "nextMilestone": "Demonstrate meaningful human clinical outcomes with acceptable safety.",
      "sourceIds": [
        "rapa"
      ]
    },
    {
      "id": "il11",
      "name": "IL11 / IL11RA — inflammatory signaling target",
      "type": "gene",
      "evidence": "animal",
      "genes": [
        "IL11",
        "IL11RA"
      ],
      "pathway": "Preserve · inflammation / fibrosis",
      "summary": "Reducing IL-11 signaling is a candidate for addressing several aging-related processes together.",
      "species": "Mouse genetic and antibody-intervention experiments",
      "outcome": "Inhibition improved multiple health measures and extended mouse lifespan.",
      "limitations": "Mouse efficacy does not prove normal human aging can be slowed by this intervention.",
      "risks": "Long-term effects on normal signaling and tissue repair need human evaluation.",
      "nextMilestone": "Complete disease-specific human studies and test relevant functional outcomes.",
      "sourceIds": [
        "il11"
      ]
    },
    {
      "id": "wrn",
      "name": "WRN — DNA-maintenance failure as a clue",
      "type": "gene",
      "evidence": "human-association",
      "genes": [
        "WRN"
      ],
      "pathway": "Repair · genome maintenance",
      "summary": "Loss of normal WRN function causes Werner syndrome, showing the importance of DNA maintenance.",
      "species": "Human inherited premature-aging disorder",
      "outcome": "Disease-causing variants disrupt a protein involved in DNA maintenance and replication.",
      "limitations": "Correcting a rare genetic disorder is distinct from improving ordinary aging in an unaffected person.",
      "risks": "Genomic instability and cancer are central concerns.",
      "nextMilestone": "Establish repair strategies that maintain genome integrity without abnormal growth.",
      "sourceIds": [
        "wrn"
      ]
    },
    {
      "id": "lmna",
      "name": "LMNA / ZMPSTE24 — nuclear-envelope pathology",
      "type": "gene",
      "evidence": "human-outcomes",
      "genes": [
        "LMNA",
        "ZMPSTE24"
      ],
      "pathway": "Repair · nuclear structure",
      "summary": "A specific nuclear-envelope disease mechanism has a disease-targeted treatment with regulatory recognition of mortality benefit.",
      "species": "Humans with HGPS or specified progeroid laminopathies",
      "outcome": "FDA approved lonafarnib for the specified indications, including reducing mortality risk in HGPS.",
      "limitations": "The indication does not establish treatment of normal aging or broad nuclear rejuvenation.",
      "risks": "Disease-specific eligibility, adverse effects and interactions remain important.",
      "nextMilestone": "Develop and validate interventions for the specific pathology before generalizing.",
      "sourceIds": [
        "progeria"
      ]
    },
    {
      "id": "retinal-osk",
      "name": "Partial reprogramming — restore a tissue function",
      "type": "therapy",
      "evidence": "animal",
      "genes": [
        "POU5F1",
        "SOX2",
        "KLF4",
        "TET1",
        "TET2"
      ],
      "pathway": "Reset · epigenetic regulation",
      "summary": "Mouse retinal experiments showed a functional recovery signal alongside epigenetic changes.",
      "species": "Mouse retinal ganglion cells and vision models",
      "outcome": "OSK expression promoted axon regeneration and improved vision in studied injury, glaucoma and aging models.",
      "limitations": "An eye result is not whole-body or human lifespan rejuvenation.",
      "risks": "Maintain neuronal identity and avoid uncontrolled or misplaced growth.",
      "nextMilestone": "Demonstrate durable human functional benefit and long-term safety.",
      "sourceIds": [
        "osk-retina"
      ]
    },
    {
      "id": "systemic-osk",
      "name": "Partial reprogramming — remaining-life endpoint",
      "type": "therapy",
      "evidence": "animal",
      "genes": [
        "POU5F1",
        "SOX2",
        "KLF4"
      ],
      "pathway": "Reset · systemic reprogramming",
      "summary": "A study in very old male mice reported an increase in remaining lifespan.",
      "species": "124-week-old male mice",
      "outcome": "The paper reports 109% greater median remaining lifespan after intervention.",
      "limitations": "Remaining lifespan is not total lifespan doubled. Sex, cohort size and replication constrain interpretation; no human forecast follows.",
      "risks": "Repeated whole-body exposure, cancer, cell identity and delivery remain unresolved.",
      "nextMilestone": "Independent replication and larger, long-term, diverse preclinical studies.",
      "sourceIds": [
        "osk-old"
      ]
    },
    {
      "id": "fibroblast-reset",
      "name": "Transient reset of human fibroblasts",
      "type": "therapy",
      "evidence": "cell",
      "genes": [
        "POU5F1",
        "SOX2",
        "KLF4",
        "MYC"
      ],
      "pathway": "Reset · cell identity / collagen",
      "summary": "Cultured human skin cells showed molecular and some functional changes after transient reprogramming.",
      "species": "Human donor fibroblasts in vitro",
      "outcome": "Age-related molecular measures, collagen production and migration assays changed toward younger patterns.",
      "limitations": "A cell-culture clock change is not years removed from a person or proven wound healing in humans.",
      "risks": "Temporary loss of identity and growth control require careful evaluation.",
      "nextMilestone": "Test stable identity and useful tissue-level repair in controlled translation.",
      "sourceIds": [
        "mptr"
      ]
    },
    {
      "id": "er100-trial",
      "name": "ER-100 — early human optic-nerve trial",
      "type": "trial",
      "evidence": "human-early",
      "genes": [
        "POU5F1",
        "SOX2",
        "KLF4"
      ],
      "pathway": "Reset · clinical translation",
      "summary": "NCT07290244 is a Phase 1 optic-neuropathy study assessing safety and tolerability.",
      "species": "People with open-angle glaucoma or NAION; planned enrollment 18",
      "outcome": "Registry search snapshot lists a single-dose early human study and no posted results.",
      "limitations": "Snapshot last posted 2026-05-19; current recruitment not independently confirmed. It does not test lifespan.",
      "risks": "Human safety, immune effects and durable visual benefit require follow-up.",
      "nextMilestone": "Read registered outcomes and peer-reviewed results as they become available.",
      "sourceIds": [
        "er100"
      ]
    },
    {
      "id": "ipsc-neurons",
      "name": "Replace lost dopamine-producing neurons",
      "type": "trial",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Replace · differentiated cell therapy",
      "summary": "Early human research supports the possibility of replacing a specialized lost cell function.",
      "species": "Open-label Phase I/II Parkinson’s study",
      "outcome": "Seven participants were assessed for safety; transplanted cells produced dopamine and no tumor overgrowth was identified over 24 months.",
      "limitations": "Small, uncontrolled disease trial; exploratory improvement is not proof of whole-brain or whole-body rejuvenation.",
      "risks": "Rejection, graft behavior, surgical risk and longer-term growth require monitoring.",
      "nextMilestone": "Larger controlled studies and sustained functional and safety follow-up.",
      "sourceIds": [
        "ipsc"
      ]
    },
    {
      "id": "senolytic-cart",
      "name": "Engineered immune clearance of senescent cells",
      "type": "therapy",
      "evidence": "animal",
      "genes": [
        "PLAUR"
      ],
      "pathway": "Clear · immune surveillance",
      "summary": "Senolytic CAR T cells are a way to redirect immune recognition toward some senescent cells.",
      "species": "Aged mice and mouse metabolic-dysfunction models",
      "outcome": "uPAR-directed cells improved glucose tolerance and exercise capacity with persistent effects in the models.",
      "limitations": "No established human anti-aging or lifespan benefit; target specificity is not universal.",
      "risks": "Off-target recognition, inflammation and depletion of useful cells require evaluation.",
      "nextMilestone": "Demonstrate specificity and safety across tissues before clinical aging claims.",
      "sourceIds": [
        "cart"
      ]
    },
    {
      "id": "healing-senescence",
      "name": "CDKN2A / PDGFA — useful transient senescence",
      "type": "gene",
      "evidence": "animal",
      "genes": [
        "CDKN2A",
        "PDGFA"
      ],
      "pathway": "Protect · wound healing",
      "summary": "Some senescent cells have useful short-term functions. A clearing strategy needs to distinguish persistent dysfunction from repair.",
      "species": "Mouse wound-healing experiments",
      "outcome": "Removing senescent cells delayed wound closure; PDGF-AA contributed to their repair-supporting effect.",
      "limitations": "A wound model does not settle which cells to clear in every aged tissue.",
      "risks": "Indiscriminate clearance could impair healing; disabling arrest can also remove a growth barrier.",
      "nextMilestone": "Identify cell state, tissue and timing that separate benefit from harm.",
      "sourceIds": [
        "healing"
      ]
    },
    {
      "id": "nmn",
      "name": "NAD precursor NMN — a metabolic endpoint",
      "type": "trial",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Repair · NAD metabolism",
      "summary": "A small randomized human study tested metabolic function rather than longevity.",
      "species": "Postmenopausal women with prediabetes, overweight or obesity",
      "outcome": "A 10-week study found increased muscle insulin sensitivity and signaling in the studied population.",
      "limitations": "No measured human lifespan extension, whole-body rejuvenation or general benefit established.",
      "risks": "Limited duration and population leave long-term and wider effects uncertain.",
      "nextMilestone": "Replicate clinically meaningful outcomes in larger studies.",
      "sourceIds": [
        "nmn"
      ]
    },
    {
      "id": "urolithin",
      "name": "Mitochondrial quality: primary endpoints matter",
      "type": "trial",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Repair · mitochondria / mitophagy",
      "summary": "Urolithin A research illustrates why primary and secondary outcomes need separate interpretation.",
      "species": "Randomized placebo-controlled trial, 66 older adults",
      "outcome": "Some muscle-endurance and biomarker results improved; 6-minute walk and maximal ATP-production primary outcomes were not significantly improved versus placebo.",
      "limitations": "Four months, small sample; no lifespan or organelle-replacement proof.",
      "risks": "Long-term benefit and population generalizability remain uncertain.",
      "nextMilestone": "Confirm meaningful function in larger, independently replicated trials.",
      "sourceIds": [
        "ua"
      ]
    },
    {
      "id": "senolytic-dq",
      "name": "Senolytic drugs — human target-engagement signal",
      "type": "trial",
      "evidence": "human-early",
      "genes": [
        "CDKN2A",
        "CDKN1A"
      ],
      "pathway": "Clear · cellular senescence",
      "summary": "A preliminary human study measured senescent-cell markers after a senolytic intervention.",
      "species": "Open-label pilot in nine people with diabetic kidney disease",
      "outcome": "Some tissue senescence markers and circulating inflammatory factors decreased.",
      "limitations": "No randomized control, limited sample and follow-up; this does not prove lifespan extension or clinical benefit.",
      "risks": "Drug toxicity, tissue specificity and beneficial senescence need evaluation.",
      "nextMilestone": "Controlled trials with meaningful outcomes and safety monitoring.",
      "sourceIds": [
        "dq"
      ]
    },
    {
      "id": "msc-frailty",
      "name": "Mesenchymal stromal cells — frailty research",
      "type": "trial",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Repair · cell-based signaling / frailty",
      "summary": "Small human frailty trials investigate cell-based interventions; this differs from replacing every aged cell.",
      "species": "Randomized placebo-controlled Phase II trial, 30 participants",
      "outcome": "The study assessed safety and frailty-related functional and inflammatory outcomes.",
      "limitations": "Early study scale and duration cannot establish human rejuvenation or survival benefit.",
      "risks": "Cell product quality, immune effects and long-term safety remain central.",
      "nextMilestone": "Replicate durable patient-important benefit in larger trials.",
      "sourceIds": [
        "msc"
      ]
    },
    {
      "id": "calerie",
      "name": "Calorie restriction — clocks and clinical endpoints",
      "type": "therapy",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Preserve · metabolism / biomarkers",
      "summary": "CALERIE provides randomized human evidence about selected molecular measures.",
      "species": "Two-year trial; 220 randomized adults, 197 in methylation analysis",
      "outcome": "DunedinPACE changed modestly; PhenoAge and GrimAge estimates did not show significant intervention changes.",
      "limitations": "This analysis did not demonstrate extra human life-years or a reversal of chronological age.",
      "risks": "Nutritional adequacy, muscle/bone effects and individual context require clinical consideration.",
      "nextMilestone": "Establish durable functional and clinical outcomes, not only surrogate shifts.",
      "sourceIds": [
        "calerie"
      ]
    },
    {
      "id": "controlled-renewal",
      "name": "Research proposal: controlled renewal loop",
      "type": "gap",
      "evidence": "hypothesis",
      "genes": [
        "TP53",
        "TERT",
        "CDKN2A"
      ],
      "pathway": "Replace + protect · system design",
      "summary": "Proposed sequence of capabilities: assess cell damage, repair salvageable function, replace selected losses, preserve cancer surveillance, then verify durable function.",
      "species": "Conceptual research framework",
      "outcome": "No validated combined human therapy or lifespan effect is asserted.",
      "limitations": "Individual component evidence does not establish a safe integrated system.",
      "risks": "Growth control, immune recognition and tissue integration can conflict.",
      "nextMilestone": "Demonstrate one repeatable repair-and-surveillance cycle with meaningful function and long follow-up.",
      "sourceIds": [
        "p53",
        "ipsc",
        "cart"
      ]
    },
    {
      "id": "brain-identity",
      "name": "Bottleneck: preserve memory and neural identity",
      "type": "gap",
      "evidence": "hypothesis",
      "genes": [],
      "pathway": "Replace · neural continuity",
      "summary": "Replacing a specialized cell function is an early foothold; preserving a person’s distributed brain function over centuries remains a research gap.",
      "species": "Research requirement, not a demonstrated therapy",
      "outcome": "A proposed success criterion is retained cognition and function, alongside cellular safety.",
      "limitations": "A dopamine-cell trial does not test replacement of arbitrary memory-bearing circuits.",
      "risks": "Network disruption, misplaced integration and loss of function.",
      "nextMilestone": "Show stable integration and preservation of relevant functions before broader replacement.",
      "sourceIds": [
        "ipsc",
        "osk-retina"
      ]
    },
    {
      "id": "matrix-niche",
      "name": "Bottleneck: renew the supporting environment",
      "type": "gap",
      "evidence": "hypothesis",
      "genes": [],
      "pathway": "Repair · extracellular matrix / niche",
      "summary": "A cell-replacement program would also need adequate vascular support, a suitable extracellular environment and reliable local signaling.",
      "species": "Conceptual tissue-engineering requirement",
      "outcome": "No systemic matrix-rejuvenation result is claimed here.",
      "limitations": "This edition has no verified human therapy that restores all aged matrices and niches.",
      "risks": "New cells may fail to integrate or function in damaged tissue.",
      "nextMilestone": "Measure tissue mechanics, perfusion, integration and useful function together.",
      "sourceIds": [
        "ipsc",
        "mptr"
      ]
    },
    {
      "id": "repeat-risk",
      "name": "Bottleneck: repeated intervention and cancer risk",
      "type": "gap",
      "evidence": "hypothesis",
      "genes": [
        "TP53",
        "TERT"
      ],
      "pathway": "Protect · long-horizon risk",
      "summary": "A successful short study cannot resolve the cumulative risks of repeated regeneration over centuries.",
      "species": "Conceptual long-term safety requirement",
      "outcome": "The atlas makes no numerical prediction of therapy-related lifetime cancer risk.",
      "limitations": "Rare late harms, changing clones and interactions require prolonged surveillance.",
      "risks": "Cancer, immune dysregulation and repeated delivery complications.",
      "nextMilestone": "Establish long-term registries, cancer surveillance and reproducible stopping criteria.",
      "sourceIds": [
        "telomere-cancer",
        "p53"
      ]
    },
    {
      "id": "validated-outcomes",
      "name": "Bottleneck: prove clinical benefit",
      "type": "gap",
      "evidence": "hypothesis",
      "genes": [],
      "pathway": "Measure · outcomes / clocks",
      "summary": "An improved molecular clock or telomere measurement is a useful observation, with separate work needed to establish a clinical benefit.",
      "species": "Evidence-evaluation requirement",
      "outcome": "Prioritize function, disease burden and survival where feasible.",
      "limitations": "There is no conversion in this app from biomarker-years to life-years gained.",
      "risks": "Surrogate changes may be misread as rejuvenation.",
      "nextMilestone": "Validate outcomes across interventions and independent populations.",
      "sourceIds": [
        "calerie",
        "ua"
      ]
    },
    {
      "id": "rpe-replacement",
      "name": "Replace a retinal support-cell layer",
      "type": "trial",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Replace · retinal pigment epithelium",
      "summary": "An autologous iPSC-derived retinal support-cell sheet was transplanted in an early human macular-degeneration study.",
      "species": "One transplanted human eye",
      "outcome": "The sheet remained intact and visual acuity was stable at one year.",
      "limitations": "Feasibility in one eye does not demonstrate restored vision, photoreceptor replacement or systemic rejuvenation.",
      "risks": "Cell quality, surgical effects, immune behavior and long-term growth require evaluation.",
      "nextMilestone": "Establish controlled functional benefit and long-term graft safety.",
      "sourceIds": [
        "rpe"
      ]
    },
    {
      "id": "reprogramming-growth-control",
      "name": "Reprogramming needs reliable growth control",
      "type": "therapy",
      "evidence": "animal",
      "genes": [
        "POU5F1",
        "SOX2",
        "KLF4",
        "MYC"
      ],
      "pathway": "Protect · cell identity / epigenetic control",
      "summary": "A mouse study demonstrated that transient reprogramming can produce tumors through altered epigenetic regulation.",
      "species": "Mouse in vivo reprogramming model",
      "outcome": "Tumors with undifferentiated dysplastic cells developed in multiple tissues.",
      "limitations": "This specific model does not show that every partial-reprogramming approach has the same risk.",
      "risks": "Stopping factor expression alone is not proof that cells have returned to a safe identity.",
      "nextMilestone": "Show stable identity, controlled proliferation and sufficiently long safety follow-up.",
      "sourceIds": [
        "reprogram-cancer"
      ]
    },
    {
      "id": "vascular-maintenance",
      "name": "VEGFA / FLT1 — support the capillary network",
      "type": "gene",
      "evidence": "animal",
      "genes": [
        "VEGFA",
        "FLT1"
      ],
      "pathway": "Repair · vascular supply",
      "summary": "Vascular maintenance is a separate requirement for keeping tissues functional during renewal.",
      "species": "Aged mice",
      "outcome": "Counteracting insufficient VEGF signaling preserved capillaries, improved perfusion and extended lifespan in the study.",
      "limitations": "No established human aging therapy or human longevity effect follows from this model.",
      "risks": "Angiogenic signaling has tissue- and disease-dependent effects; indiscriminate stimulation is not validated.",
      "nextMilestone": "Test controlled restoration of perfusion with clinical and safety outcomes.",
      "sourceIds": [
        "vascular"
      ]
    },
    {
      "id": "clonal-quality",
      "name": "DNMT3A / TET2 / ASXL1 — track blood-cell clones",
      "type": "gene",
      "evidence": "human-association",
      "genes": [
        "DNMT3A",
        "TET2",
        "ASXL1"
      ],
      "pathway": "Protect · stem-cell / clonal quality",
      "summary": "Renewing a blood system requires attention to somatic clones as well as cell quantity.",
      "species": "Human blood-exome study, 17,182 people",
      "outcome": "Age-related clonal mutations were associated with hematologic cancer, mortality and vascular outcomes.",
      "limitations": "Association does not establish that eliminating a clone prolongs life.",
      "risks": "A proliferative renewal strategy could expand an unfavorable clone.",
      "nextMilestone": "Demonstrate safe restoration of diverse functional blood-cell production.",
      "sourceIds": [
        "chip"
      ]
    },
    {
      "id": "islet-replacement",
      "name": "Replace insulin-producing islet function",
      "type": "trial",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Replace · pancreatic islet cells",
      "summary": "Stem-cell-derived differentiated islets provide another human example of specialized functional replacement.",
      "species": "Small early study in people with type 1 diabetes",
      "outcome": "The primary publication supports the hypothesis that zimislecel can restore physiologic islet function.",
      "limitations": "Disease-specific, small and short-term; it does not demonstrate healthy-person aging reversal.",
      "risks": "Immune management, adverse events and long-term graft durability require clinical evaluation.",
      "nextMilestone": "Confirm sustained benefit and safe immune protection in larger studies.",
      "sourceIds": [
        "islets"
      ]
    },
    {
      "id": "mtor-human-null",
      "name": "Human mTOR trials — include the null result",
      "type": "trial",
      "evidence": "human-early",
      "genes": [
        "MTOR"
      ],
      "pathway": "Preserve · immune function",
      "summary": "Human pathway modulation produced mixed trial outcomes, illustrating the need for endpoint-specific interpretation.",
      "species": "Randomized Phase 2b and Phase 3 trials in older adults",
      "outcome": "Some Phase 2b analyses favored fewer laboratory-confirmed infections; the Phase 3 trial did not significantly reduce its symptomatic respiratory-illness endpoint.",
      "limitations": "Neither study establishes lifespan extension or whole-body rejuvenation.",
      "risks": "Molecular response can occur without the intended clinical benefit.",
      "nextMilestone": "Use replicated, prespecified clinical outcomes and appropriate populations.",
      "sourceIds": [
        "mtor-human"
      ]
    },
    {
      "id": "dohealth-clocks",
      "name": "DO-HEALTH — small molecular clock shifts",
      "type": "therapy",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Preserve · lifestyle / biomarkers",
      "summary": "A randomized-trial subanalysis evaluated vitamin D, omega-3 and exercise using methylation clocks.",
      "species": "Older adults; Swiss DO-HEALTH biomarker subcohort",
      "outcome": "Omega-3 showed small changes in several clocks; combined interventions had an additive PhenoAge signal.",
      "limitations": "Clock changes are not measured life-years gained, and a subanalysis does not establish extreme longevity.",
      "risks": "Endpoint selection, subgroup analysis and clinical relevance affect interpretation.",
      "nextMilestone": "Link durable molecular findings to meaningful functional and clinical outcomes.",
      "sourceIds": [
        "dohealth"
      ]
    },
    {
      "id": "thymic-research",
      "name": "Thymic renewal — an uncontrolled pilot",
      "type": "trial",
      "evidence": "human-early",
      "genes": [],
      "pathway": "Repair · immune-system renewal",
      "summary": "A small combined-intervention study reported thymic imaging, immune and methylation-clock changes.",
      "species": "One-year pilot in nine middle-aged men",
      "outcome": "Several immune and clock measures changed relative to baseline.",
      "limitations": "No placebo group and multiple simultaneous interventions; no measured lifespan extension.",
      "risks": "Hormonal and metabolic effects and cancer-related safety require separate evaluation.",
      "nextMilestone": "Replicate with controlled trials that separate component effects and measure useful immune function.",
      "sourceIds": [
        "triim"
      ]
    }
  ],
  "sources": [
    {
      "id": "telomere-mouse",
      "title": "Bernardes de Jesus et al. — Telomerase gene therapy in adult and old mice",
      "url": "https://pubmed.ncbi.nlm.nih.gov/22585399/",
      "year": 2012,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "telomere-cancer",
      "title": "Telomeres MR Collaboration — Telomere length, cancer and non-neoplastic disease",
      "url": "https://pubmed.ncbi.nlm.nih.gov/28241208/",
      "year": 2017,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "p53",
      "title": "García-Cao et al. — Regulated extra p53 copies, cancer resistance and normal aging in mice",
      "url": "https://pubmed.ncbi.nlm.nih.gov/12426394/",
      "year": 2002,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "foxo3",
      "title": "Willcox et al. — FOXO3A genotype and human longevity",
      "url": "https://pubmed.ncbi.nlm.nih.gov/18765803/",
      "year": 2008,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "apoe",
      "title": "Deelen et al. — Meta-analysis of human longevity genetics",
      "url": "https://www.nature.com/articles/s41467-019-11558-2",
      "year": 2019,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "igf",
      "title": "Suh et al. — Functional IGF1R mutations in centenarians",
      "url": "https://pubmed.ncbi.nlm.nih.gov/18316725/",
      "year": 2008,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "ghr",
      "title": "Guevara-Aguirre et al. — GHR deficiency, cancer and diabetes in humans",
      "url": "https://pubmed.ncbi.nlm.nih.gov/21325617/",
      "year": 2011,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "sirt6",
      "title": "Roichman et al. — SIRT6, energy homeostasis and healthy lifespan",
      "url": "https://www.nature.com/articles/s41467-021-23545-7",
      "year": 2021,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "atg5",
      "title": "Pyo et al. — Atg5 overexpression, autophagy and mouse lifespan",
      "url": "https://www.nature.com/articles/ncomms3300",
      "year": 2013,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "rapa",
      "title": "Harrison et al. — Late-life rapamycin in genetically heterogeneous mice",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2786175/",
      "year": 2009,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "il11",
      "title": "Widjaja et al. — IL-11 inhibition and mammalian lifespan",
      "url": "https://www.nature.com/articles/s41586-024-07701-9",
      "year": 2024,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "wrn",
      "title": "NIH MedlinePlus Genetics — Werner syndrome and WRN",
      "url": "https://medlineplus.gov/genetics/condition/werner-syndrome/",
      "year": 2021,
      "kind": "official-database",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "progeria",
      "title": "FDA — Lonafarnib approval for HGPS and processing-deficient progeroid laminopathies",
      "url": "https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=333411",
      "year": 2020,
      "kind": "regulator",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "osk-retina",
      "title": "Lu et al. — Reprogramming, epigenetic information and restored mouse vision",
      "url": "https://www.nature.com/articles/s41586-020-2975-4",
      "year": 2020,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "osk-old",
      "title": "Cano Macip et al. — Partial reprogramming in very old male mice",
      "url": "https://pubmed.ncbi.nlm.nih.gov/38381405/",
      "year": 2024,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "mptr",
      "title": "Gill et al. — Transient reprogramming of human fibroblasts",
      "url": "https://pubmed.ncbi.nlm.nih.gov/35390271/",
      "year": 2022,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "er100",
      "title": "ClinicalTrials.gov — NCT07290244, ER-100 Phase 1 optic-neuropathy study",
      "url": "https://clinicaltrials.gov/study/NCT07290244",
      "year": 2026,
      "kind": "trial-registry",
      "checked": "2026-11-01",
      "access": "Indexed registry snapshot: last update posted 2026-05-19. Direct dynamic page/API did not expose a fresh complete record; current recruitment not independently confirmed."
    },
    {
      "id": "ipsc",
      "title": "Sawamoto et al. — Phase I/II iPS-derived dopamine-cell trial in Parkinson’s disease",
      "url": "https://www.nature.com/articles/s41586-025-08700-0",
      "year": 2025,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "cart",
      "title": "Amor et al. — Senolytic CAR T cells and age-related metabolic dysfunction",
      "url": "https://pubmed.ncbi.nlm.nih.gov/38267706/",
      "year": 2024,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "healing",
      "title": "Demaria et al. — Senescent cells, PDGF-AA and wound healing",
      "url": "https://pubmed.ncbi.nlm.nih.gov/25499914/",
      "year": 2014,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "nmn",
      "title": "Yoshino et al. — NMN and muscle insulin sensitivity in prediabetic women",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33888596/",
      "year": 2021,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "ua",
      "title": "Liu et al. — Urolithin A randomized trial: primary and secondary muscle outcomes",
      "url": "https://pubmed.ncbi.nlm.nih.gov/35050355/",
      "year": 2022,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "dq",
      "title": "Hickson et al. — Preliminary human senolytic study in diabetic kidney disease",
      "url": "https://pubmed.ncbi.nlm.nih.gov/31542391/",
      "year": 2019,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "msc",
      "title": "Tompkins et al. — Randomized Phase II mesenchymal stromal-cell frailty trial",
      "url": "https://pubmed.ncbi.nlm.nih.gov/28977399/",
      "year": 2017,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "calerie",
      "title": "Waziry et al. — CALERIE randomized trial and DNA-methylation measures",
      "url": "https://www.nature.com/articles/s43587-022-00357-y",
      "year": 2023,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "rpe",
      "title": "Mandai et al. — Autologous stem-cell-derived retinal cells for macular degeneration",
      "url": "https://pubmed.ncbi.nlm.nih.gov/28296613/",
      "year": 2017,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "reprogram-cancer",
      "title": "Ohnishi et al. — Interrupted in vivo reprogramming and epigenetic tumor development",
      "url": "https://pubmed.ncbi.nlm.nih.gov/24529372/",
      "year": 2014,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "vascular",
      "title": "Grunewald et al. — VEGF signaling, vascular maintenance and mouse lifespan",
      "url": "https://pubmed.ncbi.nlm.nih.gov/34326210/",
      "year": 2021,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "chip",
      "title": "Jaiswal et al. — Clonal hematopoiesis and adverse outcomes",
      "url": "https://pubmed.ncbi.nlm.nih.gov/25426837/",
      "year": 2014,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "islets",
      "title": "Reichman et al. — Stem-cell-derived fully differentiated islets for type 1 diabetes",
      "url": "https://www.nejm.org/doi/10.1056/NEJMoa2506549",
      "year": 2025,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "mtor-human",
      "title": "Mannick et al. — mTOR inhibitors: Phase 2b and Phase 3 randomized trials",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33977284/",
      "year": 2021,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "dohealth",
      "title": "Bischoff-Ferrari et al. — DO-HEALTH interventions and DNA-methylation clocks",
      "url": "https://www.nature.com/articles/s43587-024-00793-y",
      "year": 2025,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "triim",
      "title": "Fahy et al. — Thymic and epigenetic-aging pilot observations",
      "url": "https://pubmed.ncbi.nlm.nih.gov/31496122/",
      "year": 2019,
      "kind": "primary-study",
      "checked": "2026-11-01",
      "access": "Primary publication abstract/indexed page or official source; selected research, not exhaustive."
    },
    {
      "id": "candidates-niedernhofer2006",
      "title": "A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis",
      "url": "https://doi.org/10.1038/nature05456",
      "year": 2006,
      "kind": "primary-research"
    },
    {
      "id": "candidates-mao2011",
      "title": "SIRT6 promotes DNA repair under stress by activating PARP1",
      "url": "https://doi.org/10.1126/science.1202723",
      "year": 2011,
      "kind": "primary-research"
    },
    {
      "id": "candidates-kanfi2012",
      "title": "The sirtuin SIRT6 regulates lifespan in male mice",
      "url": "https://doi.org/10.1038/nature10815",
      "year": 2012,
      "kind": "primary-research"
    },
    {
      "id": "candidates-jaskelioff2011",
      "title": "Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice",
      "url": "https://doi.org/10.1038/nature09603",
      "year": 2011,
      "kind": "primary-research"
    },
    {
      "id": "candidates-chin1999",
      "title": "p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis",
      "url": "https://pubmed.ncbi.nlm.nih.gov/10338216/",
      "year": 1999,
      "kind": "primary-research"
    },
    {
      "id": "candidates-harrison2009",
      "title": "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice",
      "url": "https://doi.org/10.1038/nature08221",
      "year": 2009,
      "kind": "primary-research"
    },
    {
      "id": "candidates-mannick2018",
      "title": "TORC1 inhibition enhances immune function and reduces infections in the elderly",
      "url": "https://doi.org/10.1126/scitranslmed.aaq1564",
      "year": 2018,
      "kind": "primary-research"
    },
    {
      "id": "candidates-pyo2013",
      "title": "Overexpression of Atg5 in mice activates autophagy and extends lifespan",
      "url": "https://doi.org/10.1038/ncomms3300",
      "year": 2013,
      "kind": "primary-research"
    },
    {
      "id": "candidates-ho2017",
      "title": "Autophagy maintains the metabolism and function of young and old stem cells",
      "url": "https://doi.org/10.1038/nature21388",
      "year": 2017,
      "kind": "primary-research"
    },
    {
      "id": "candidates-zhang2008",
      "title": "Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function",
      "url": "https://doi.org/10.1038/nm.1851",
      "year": 2008,
      "kind": "primary-research"
    },
    {
      "id": "candidates-trifunovic2004",
      "title": "Premature ageing in mice expressing defective mitochondrial DNA polymerase",
      "url": "https://doi.org/10.1038/nature02517",
      "year": 2004,
      "kind": "primary-research"
    },
    {
      "id": "candidates-kujoth2005",
      "title": "Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging",
      "url": "https://doi.org/10.1126/science.1112125",
      "year": 2005,
      "kind": "primary-research"
    },
    {
      "id": "candidates-miller2005",
      "title": "Evaluating evidence for aging",
      "url": "https://pubmed.ncbi.nlm.nih.gov/16239461/",
      "year": 2005,
      "kind": "comment"
    },
    {
      "id": "candidates-narendra2008",
      "title": "Parkin is recruited selectively to impaired mitochondria and promotes their autophagy",
      "url": "https://doi.org/10.1083/jcb.200809125",
      "year": 2008,
      "kind": "primary-research"
    },
    {
      "id": "candidates-narendra2010",
      "title": "PINK1 is selectively stabilized on impaired mitochondria to activate Parkin",
      "url": "https://doi.org/10.1371/journal.pbio.1000298",
      "year": 2010,
      "kind": "primary-research"
    },
    {
      "id": "candidates-ryu2016",
      "title": "Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents",
      "url": "https://doi.org/10.1038/nm.4132",
      "year": 2016,
      "kind": "primary-research"
    },
    {
      "id": "candidates-andreux2019",
      "title": "The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans",
      "url": "https://pubmed.ncbi.nlm.nih.gov/32694802/",
      "year": 2019,
      "kind": "primary-research"
    },
    {
      "id": "candidates-ocampo2016",
      "title": "In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming",
      "url": "https://doi.org/10.1016/j.cell.2016.11.052",
      "year": 2016,
      "kind": "primary-research"
    },
    {
      "id": "candidates-ohnishi2014",
      "title": "Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation",
      "url": "https://doi.org/10.1016/j.cell.2014.01.005",
      "year": 2014,
      "kind": "primary-research"
    },
    {
      "id": "candidates-baker2011",
      "title": "Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders",
      "url": "https://doi.org/10.1038/nature10600",
      "year": 2011,
      "kind": "primary-research"
    },
    {
      "id": "candidates-baker2016",
      "title": "Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan",
      "url": "https://doi.org/10.1038/nature16932",
      "year": 2016,
      "kind": "primary-research"
    },
    {
      "id": "candidates-demaria2014",
      "title": "An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA",
      "url": "https://doi.org/10.1016/j.devcel.2014.11.012",
      "year": 2014,
      "kind": "primary-research"
    },
    {
      "id": "candidates-demaria2014-eoc",
      "title": "Expression of concern: An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA",
      "url": "https://doi.org/10.1016/j.devcel.2026.04.004",
      "year": 2026,
      "kind": "expression-of-concern"
    },
    {
      "id": "candidates-garciacao2002",
      "title": "Super p53 mice exhibit enhanced DNA damage response, are tumor resistant and age normally",
      "url": "https://doi.org/10.1093/emboj/cdf595",
      "year": 2002,
      "kind": "primary-research"
    },
    {
      "id": "candidates-tyner2002",
      "title": "p53 mutant mice that display early ageing-associated phenotypes",
      "url": "https://doi.org/10.1038/415045a",
      "year": 2002,
      "kind": "primary-research"
    },
    {
      "id": "candidates-conboy2005",
      "title": "Rejuvenation of aged progenitor cells by exposure to a young systemic environment",
      "url": "https://doi.org/10.1038/nature03260",
      "year": 2005,
      "kind": "primary-research"
    },
    {
      "id": "candidates-kusumbe2014",
      "title": "Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone",
      "url": "https://doi.org/10.1038/nature13145",
      "year": 2014,
      "kind": "primary-research"
    },
    {
      "id": "candidates-rossi2005",
      "title": "Cell intrinsic alterations underlie hematopoietic stem cell aging",
      "url": "https://doi.org/10.1073/pnas.0503280102",
      "year": 2005,
      "kind": "primary-research"
    },
    {
      "id": "candidates-anzalone2019",
      "title": "Search-and-replace genome editing without double-strand breaks or donor DNA",
      "url": "https://doi.org/10.1038/s41586-019-1711-4",
      "year": 2019,
      "kind": "primary-research"
    },
    {
      "id": "failures-donehower-1992",
      "title": "Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours",
      "url": "https://doi.org/10.1038/356215a0",
      "year": 1992,
      "kind": "primary-paper"
    },
    {
      "id": "failures-garcia-cao-2002",
      "title": "\"Super p53\" mice exhibit enhanced DNA damage response, are tumor resistant and age normally",
      "url": "https://doi.org/10.1093/emboj/cdf595",
      "year": 2002,
      "kind": "primary-paper"
    },
    {
      "id": "failures-tyner-2002",
      "title": "p53 mutant mice that display early ageing-associated phenotypes",
      "url": "https://doi.org/10.1038/415045a",
      "year": 2002,
      "kind": "primary-paper"
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