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ABSTRACT Background The twelve hallmarks of aging as defined by López-Otín et al. ( Cell , 2023) represent the primary, antagonistic, and integrative mechanisms driving biological aging. To our knowledge, no open-source preclinical framework has yet attempted to coordinate all 12 official hallmarks in a single modular, non-integrating, safety-gated design validated across tens of thousands of computational cycles. This manuscript presents The Cepeda Framework — a modular, safety-first preclinical research program designed to test whether coordinated partial rejuvenation strategies can be pursued in a falsifiable and systematically safety-constrained manner. Computational Development The framework was developed through 21,000 dual-validation simulation cycles — each simultaneously testing Efficacy (epigenetic reversal) and Safety (NANOG induction prevention) — executed by the Forward Thinking Communities Scientific Group over one year of intensive computational modeling. The program evolved through four distinct phases: from the original Genesis Framework single-hallmark concept (Cycles 1–5,000; FAILURE — 1:1:1 ratio unsafe), through stoichiometric ratio optimization (Cycles 5,001–12,000; PIVOT — 3:2:1 ratio locked), gate verification (Cycles 12,001–18,000; SUCCESS — dual-miRNA logic validated), and final 12-hallmark integration (Cycles 18,001–21,000; CONVERGENCE — Cepeda Framework finalized). Framework The Cepeda Framework integrates five regulatory principles — (I) stoichiometric 3:2:1 OCT4:SOX2:KLF4 polycistronic m1Ψ-saRNA; (II) 72-hour intrinsic saRNA pulse; (III) LEAD-7294 dual-miRNA logic gate (kill-switch + Let-7/L7Ae/Kt activation gate); (IV) NRF2/NAD + /paracrine microenvironmental co-treatment; (V) Genesis-TERT-01 transient hTERT telomere restoration — with five companion protocols (Rapamycin pulse, Metformin, AP39 H2S donor [HIGH-UNCERTAINTY; Tier 1A required], GGA/4-PBA proteostasis stack, and Akkermansia/synbiotic/butyrate dysbiosis correction). Together, these components map to all 12 official López-Otín 2023 hallmarks plus one Copenhagen 2022 candidate hallmark (RNA splicing dysregulation). Safety Nine parallel and sequential safety safeguards ensure no single-point failure produces uncontrolled reprogramming or sustained exposure, including the embedded LEAD-7294 miR-294 kill-switch (predicted t½ <12 min at >5,000 copies/cell), the proactive Let-7/L7Ae/Kt activation gate, intrinsic saRNA transience, the 3:2:1 stoichiometric brake, and a predefined Acute Cytokine Response (ACR) monitoring protocol. All companion agents are clinically approved or have established in vitro/in vivo safety profiles . Status Theoretical preclinical framework. No wet-laboratory validation of the integrated protocol has been conducted. All quantitative predictions require experimental falsification. Validation proceeds through a five-tier modular preclinical roadmap beginning with aged human dermal fibroblasts. All simulation code and archives will be released under CC0 at or before preprint submission.