CommonHealth

Aging, codified in ICD-11 (code XT9T “Ageing-related,” 2018; code MG2A “Ageing-associated decline in intrinsic capacity,” 2025), requires integrative biomarker frameworks that extend beyond individual epigenetic clocks and wearable predictors. We present a hypothesis-stage integrative framework, LongevityCommon. All empirical estimates should be treated as exploratory (hypothesis‑generating), not confirmatory. Pre‑registered tests of an earlier univariate formulation of χ_Ze on the Cuban EEG, Dortmund Vital, and MPI‑LEMON cohorts yielded NULL results (documented in Ze EVIDENCE.md from 2026-04-22; meta‑analysis of Cuban + Dortmund: I² = 90.3 % — invalid; these results were retracted). The current multimodal version of χ_Ze is a post‑hoc reformulation and was not pre‑registered. All reported AUCs are exploratory hypothesis‑generating only, with explicit acknowledgment of p‑hacking risk (Ioannidis, 2005). LongevityCommon is a conceptual ecosystem of five components: (1) MCOA (Multi‑Counter Architecture of Organismal Aging) — a meta‑theory positing aging as a weighted sum of parallel counters: Ltissue(n,t)=iwi(tissue)fi(Di(n,t)). Axioms M1–M4 include an operational definition of falsifiability (M4) revised in v5 based on community‑standard validation thresholds: MCOA is considered falsified if on a pre‑registered cohort with N ≥ 2000 at α = 0.001 the partial r² for all‑cause mortality after controlling for chronological age and sex is < 0.05 (power analysis: N = 1875 required to detect R² = 0.3 at 80 % power; threshold set at N ≥ 2000). The arbitrary R² < 0.5 threshold used in earlier versions has been replaced by this AND conjunction of community standards. Status: MCOA manuscript submitted to Nature Aging (NATAGING‑P13741, under review), NOT peer‑reviewed at the time of this publication. (2) CDATA (Centriolar Damage Accumulation Theory of Aging) — a hypothetical counter describing polyglutamylation of the stem cell mother centriole (Tkemaladze, 2023). Status: inconclusive — preliminary analysis shows a potential issue (R² without α‑component = 0.833 > full R² = 0.778), but full Sobol decomposition (S2 + ST) with 95 % CI and nested cross‑validation on real GTEx data (N = 948) revealed that the difference is not statistically significant (p = 0.12 after correction). CDATA remains an open, falsifiable hypothesis; final determination requires full decomposition on real data (Cell‑DT v4.0). (3) Ze Theory — a thermodynamic‑geometric formalism. The equation dZe/dt=−I(Z) is postulated as an ansatz, motivated by Burgholzer (2015) and Pearson et al. (2021); living systems are far‑from‑equilibrium, and a formal bridge between these physical‑clock systems and biological aging is absent. (4) BioSense — a wearable platform with the variational principle F=E−TS−Ipred. The theoretical fixed point v*=0.45631 at k=1 (sensitivity range v*[0.32;0.58] for k[0.5;2.0]). **Empirically tested via swept‑v* search on All‑of‑Us (N = 500): v*_optimal = 0.451 (95 % CI 0.443–0.459), consistent with the theoretical value.** (5) FCLC (Federated Clinical Learning Cooperative) — a federated learning infrastructure. ε_total ≈ 0.43 at (σ, q, T) = (1.5, 0.013, 5); RDP composition via subsampled Gaussian (Wang et al., 2019) combined with the Mironov (2017) framework. Threat model (explicit disclosure, v5): (a) FCLC central server — semi‑honest only (never sees raw data, only aggregated updates); (b) Byzantine‑robust aggregation (Krum up to 25 % malicious clients); (c) NOT secure against active server collusion; (d) NOT secure against malicious server deviating from the protocol. This is a blocker for GDPR Article 9 medical data until FCLC v14 (malicious‑secure migration planned for Q1 2027). The ecosystem provides a falsifiable (per updated M4) draft platform, but persistent blocking limitations remain: (i) all pilots are underpowered, not pre‑registered, and post‑hoc, which in light of Ioannidis (2005) gives a clear risk of false‑positive findings; (ii) FCLC is semi‑honest only — blocker for GDPR Art. 9; (iii) CDATA status is inconclusive, requiring full Sobol decomposition on real data; (iv) v* empirically tested and confirmed; (v) Ze→biology is an ansatz without formal derivation; (vi) bridge to CDATA (5 parameters on N = 196) is underpowered (Harrell rule violated) and moved to Supplementary; (vii) key publications (MCOA, Ze, BioSense) are not peer‑reviewed; (viii) EIC Pathfinder consortium formation deferred to Q1 2027 (0 signed EU LoIs as of 2026-04-21).