Continuous Observability of Human Biological Age through Ontological Binding of Molecular Diagnostics and Digital Physiology
Fuente:
Zenodo
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Recurso digital |
| Sprache: | Englisch |
| Veröffentlicht: |
Zenodo
2026
|
| Schlagworte: | |
| Online-Zugang: | |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| _version_ | 1866901912874385408 |
|---|---|
| author | Park, Sang hyun |
| author_facet | Park, Sang hyun |
| contents | <p class="MsoNormal"><span>Biological aging is continuous. Its clinical measurement is not. Epigenetic clocks derived from DNA methylation now estimate biological age with high precision, but methylation assays are practically sampled once per year at most. Over the same interval, the interventions these clocks are designed to evaluate — nutrition, sleep, exercise, pharmacological gerotherapeutics — operate on timescales of hours to days. This six-order-of-magnitude mismatch has left individual-scale geroprotection clinically unfalsifiable.</span></p> <p class="MsoNormal"><span>We present TCP-BioSync, a framework that closes the gap by mathematically binding clinical-grade molecular diagnostics to continuous smartphone-derived physiological signals. The core construct is an ontological binding operator ⊗ with three provable properties — baseline preservation, monotonicity, and boundedness — under which three real-time aging indices arise: a metabolic energy index (MELI) tied to mitochondrial markers, an inflammaging index (RIAI) tied to chronic inflammation and senescent-cell clearance, and Live ΔmAge, a continuous-time extension of Horvath-family epigenetic clocks. A SHA-256 hash chain (Trust Code Package, TCP) secures every committed measurement, conferring medical-record–grade integrity.</span></p> <p class="MsoNormal"><span>A pre-registered Monte Carlo validation (N = 1,000 in-silico subjects; seed 42; 3.6 × 10⁶ total engine evaluations) demonstrated construct validity between molecular baseline and physiological output at |r| = 0.85, test–retest reliability at ICC(A,1) = 0.81, biologically coherent age-cohort stratification, and 100 % hash-chain integrity. A two-phase clinical translation programme with pre-registered ICC ≥ 0.75 acceptance criterion on Live ΔmAge against re-measured MethAge-5 at twelve weeks renders the framework's principal hypothesis directly testable. The complete reference implementation is released as open-source Python with zero external dependencies. TCP-BioSync provides, to our knowledge, the first operationally defined bridge between intermittent molecular diagnostics and continuous digital physiology that is simultaneously mathematically rigorous, clinically testable, and cryptographically secured.</span></p> <h3><strong><em><span>Keywords</span></em></strong></h3> <p class="MsoNormal"><em><span>biological age; epigenetic clock; digital biomarkers; remote photoplethysmography; heart rate variability; hallmarks of aging; ontological binding; computational geroscience; Horvath clock; hash-chain integrity; precision medicine; Yamanaka factors; inflammaging; DunedinPACE.</span></em></p> <p><span> </span></p> <p class="MsoNormal"><span> </span></p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19695163 |
| institution | Zenodo |
| language | eng |
| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Continuous Observability of Human Biological Age through Ontological Binding of Molecular Diagnostics and Digital Physiology Park, Sang hyun biological age; epigenetic clock; digital biomarkers; <p class="MsoNormal"><span>Biological aging is continuous. Its clinical measurement is not. Epigenetic clocks derived from DNA methylation now estimate biological age with high precision, but methylation assays are practically sampled once per year at most. Over the same interval, the interventions these clocks are designed to evaluate — nutrition, sleep, exercise, pharmacological gerotherapeutics — operate on timescales of hours to days. This six-order-of-magnitude mismatch has left individual-scale geroprotection clinically unfalsifiable.</span></p> <p class="MsoNormal"><span>We present TCP-BioSync, a framework that closes the gap by mathematically binding clinical-grade molecular diagnostics to continuous smartphone-derived physiological signals. The core construct is an ontological binding operator ⊗ with three provable properties — baseline preservation, monotonicity, and boundedness — under which three real-time aging indices arise: a metabolic energy index (MELI) tied to mitochondrial markers, an inflammaging index (RIAI) tied to chronic inflammation and senescent-cell clearance, and Live ΔmAge, a continuous-time extension of Horvath-family epigenetic clocks. A SHA-256 hash chain (Trust Code Package, TCP) secures every committed measurement, conferring medical-record–grade integrity.</span></p> <p class="MsoNormal"><span>A pre-registered Monte Carlo validation (N = 1,000 in-silico subjects; seed 42; 3.6 × 10⁶ total engine evaluations) demonstrated construct validity between molecular baseline and physiological output at |r| = 0.85, test–retest reliability at ICC(A,1) = 0.81, biologically coherent age-cohort stratification, and 100 % hash-chain integrity. A two-phase clinical translation programme with pre-registered ICC ≥ 0.75 acceptance criterion on Live ΔmAge against re-measured MethAge-5 at twelve weeks renders the framework's principal hypothesis directly testable. The complete reference implementation is released as open-source Python with zero external dependencies. TCP-BioSync provides, to our knowledge, the first operationally defined bridge between intermittent molecular diagnostics and continuous digital physiology that is simultaneously mathematically rigorous, clinically testable, and cryptographically secured.</span></p> <h3><strong><em><span>Keywords</span></em></strong></h3> <p class="MsoNormal"><em><span>biological age; epigenetic clock; digital biomarkers; remote photoplethysmography; heart rate variability; hallmarks of aging; ontological binding; computational geroscience; Horvath clock; hash-chain integrity; precision medicine; Yamanaka factors; inflammaging; DunedinPACE.</span></em></p> <p><span> </span></p> <p class="MsoNormal"><span> </span></p> |
| title | Continuous Observability of Human Biological Age through Ontological Binding of Molecular Diagnostics and Digital Physiology |
| topic | biological age; epigenetic clock; digital biomarkers; |
| url | https://doi.org/10.5281/zenodo.19695163 |