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Longevity Evidence
m516 LongProof — aging-biology evidence claim cards (CC BY-NC 4.0).
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SymphonyAge: An 11-System DNA Methylation Age Captures System-Specific Aging Trajectories
h03_epigenetic_alterationsKCC2 Hypofunction Unifies Network Disinhibition Across Epilepsy, Neuropathic Pain, Spinal Cord Injury, and Alzheimer's-Associated Hyperexcitability
h10_altered_intercellular_communicationPhotograph-Derived Biological Age (FaceAge) Is Associated with Mortality and Cancer Outcomes; Face Aging Rate Adds Longitudinal Prognostic Information
h10_altered_intercellular_communicationOral Semaglutide Did Not Slow Alzheimer's Progression in Phase 3 (EVOKE / EVOKE+); GLP-1 Agonists Retain Cardiovascular + Metabolic + Parkinson Phase-2 Signals
h11_chronic_inflammationAPOE4 Systemically Disrupts Cholesterol Transport and Reduces Myelination via Oligodendrocyte Dysfunction; ABCA7 Loss-of-Function Disrupts Phosphatidylcholine Metabolism and Mitochondrial Function in Neurons
h03_epigenetic_alterationsMitochondrial Dysfunction as a Cross-Domain Hub Linking Aging Biology, Parkinson Disease, Kidney Disease, and Metabolic Syndrome
h07_mitochondrial_dysfunctioniPSC-Derived Thymus Organoids as a Preclinical Platform for Restoring Immune-Aging Capacity and Inducing Antigen-Specific Tolerance
h10_altered_intercellular_communicationOral Brain-Penetrant NLRP3 Inflammasome Inhibition (BGE-102) as Clinically-Ready Aging-Biology-Derived Pharmacology
h11_chronic_inflammationPersistent Pathogen Burden as a Candidate Aging Accelerator (Long COVID and Latent Herpesvirus Reservoirs as Strongest Anchors)
h11_chronic_inflammationAI-Driven Single-Cell Circuitry as Methodology for Cell-Type-Resolved Brain-Aging Atlases
h03_epigenetic_alterationsFoundation Models on DNA Methylation (CpGPT and Successors) as Cross-Tissue Aging Biomarker Substrate
h03_epigenetic_alterationsCellular Senescence-Targeted Therapeutics (Senolytics) in 2026: Selected Positive Phase 2 Signal Alongside Multiple Mixed and Negative Readouts
h08_cellular_senescencePartial Epigenetic Reprogramming (in vivo OSK / OSKM) as Long-Horizon Therapeutic Direction: First IND Cleared, Clinical Validation Years Away
h03_epigenetic_alterationsGLP-1 Receptor Agonism Across Disease Domains: Positive Cardiometabolic Outcomes Coexist with Negative Symptomatic Alzheimer Disease Readouts
h06_deregulated_nutrient_sensingFour-Layer CNS Biomarker Stratification (Exposure → Target Engagement → Pathway → Clinical) Explains Repeated Late-Stage CNS Trial Failures
h10_altered_intercellular_communicationPsychedelic Medicine Maturity in 2026: Phase 3 Positive Signal, Major M&A, and a Care-Delivery Bottleneck
h10_altered_intercellular_communicationSpeed-of-Processing Cognitive Training in the ACTIVE Trial Shows a ~29% Relative Reduction in Dementia Risk at 10-Year Follow-Up
h10_altered_intercellular_communicationIntensive Multimodal Lifestyle Intervention (Ornish 2024) in MCI / Early Alzheimer Disease Shows Cognition and Function Improvement in a Small Phase 2 RCT
h06_deregulated_nutrient_sensingPhosphatidylcholine Metabolism and Neuronal Membrane Fluidity as a Pre-Symptomatic Alzheimer Disease Mechanism Hypothesis
h04_loss_of_proteostasisAcetylcholinesterase Inhibitors (Donepezil, Rivastigmine, Galantamine) Preserve Synaptic Acetylcholine, They Do NOT Supply Choline (Boundary Pedagogical Card)
h10_altered_intercellular_communicationBTK Inhibition (Tolebrutinib HERCULES Phase 3) Delays Disability Progression in Non-Relapsing Secondary Progressive Multiple Sclerosis with Liver-Safety Monitoring Requirement
h11_chronic_inflammationAnti-Amyloid Antibodies (Lecanemab and Donanemab) Are FDA-Approved with Disproportionate ARIA Risk in ApoE ε4 Homozygotes and Substantial Payer / Screening Complexity
h04_loss_of_proteostasisFDA-Cleared Blood-Based Alzheimer Disease Biomarker (Lumipulse pTau217 / Aβ42 Ratio, May 2025) Is a Specialist-Setting Aid in Symptomatic Adults 55+, NOT Population Screening
h04_loss_of_proteostasisSkin and Cutaneous Microbiome as Candidate Visible-Phenotype Biomarkers of Systemic Aging
h10_altered_intercellular_communicationFDA's 2025 Roadmap to Reduce Mandatory Animal Testing for Monoclonal Antibodies via Validated New Approach Methodologies (NAMs) Reflects Regulatory Acceptance, Not Immediate Elimination
methodology'Younger-for-Longer' (Healthspan) vs 'Live-Longer' (Lifespan) Framing in 2026 Geroscience: Healthspan as Primary Translational Endpoint
methodology