Journal Article Ahead of print
PubMed: 42295084 DOI: 10.14336/AD.2026.0468
Epigenetic Clocks in the Cosmic Silence of a Deep Underground Laboratory: Implications for Aging and Space Exploration.
Aging Dis
Authors: Javier A Menendez, Carlos Peña-Garay, Tomás Alarcón, Elisabet Cuyàs
Affiliations
- Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, 17007 Girona, Spain.
- Metabolism and Cancer Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Girona, Spain.
- Laboratorio Subterráneo de Canfranc, 22880 Canfranc-Estación, Huesca, Spain. Institute for Integrative Systems Biology (I2SysBio), CSIC-Universitat de València, 46980 Paterna, Spain.
- Centre de Recerca Matemàtica (CRM), 08193 Bellaterra, Barcelona, Spain.
- ICREA, 08010 Barcelona, Spain.
- Departament de Matemàtiques, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Abstract
DNA methylation aging clocks are among the most accurate biomarkers of chronological and biological age, yet why the methylome encodes time with reproducible precision remains unclear. Current models emphasize developmental patterning, imperfect epigenetic maintenance, chromatin drift, and remodeling associated with DNA repair. However, they do not consider whether the persistent physical noise from Earth's radiation environment contributes to clock variance or coherence. Here, we propose DEEP-CLOCK, an experimental framework that uses the deep underground laboratory (LSC-DUL) at Canfranc (Spain) as a natural protector from a primary external stochastic input, namely surface-level cosmic-ray muons. DULs suppress the muon component of cosmic-ray background radiation by several orders of magnitude without eliminating endogenous biochemical noise and other radiation sources. This enables DNA methylation clocks to be interrogated as noise-limited biosensors by measuring mean epigenetic-age trajectories, clock-CpG variance, and methylation entropy under matched underground and above-ground conditions. Two outcomes are envisioned. Muon depletion may narrow clock variance while preserving the mean trajectory, which is consistent with improved timekeeping precision. Alternatively, muon depletion could reveal structured drift, altered slopes, or metastable offsets, suggesting that extreme radiobiological quietness could destabilize clock coherence. Neither outcome would by itself imply slowed aging, rejuvenation, or improved function alone. However, DEEP-CLOCK will test whether epigenetic clock behavior is fully intrinsic or partly calibrated by chronic low-dose radiobiological background. This reductionist framework could clarify the physical constraints on epigenetic timekeeping and inform how aging clocks function in shielded terrestrial, lunar, and Martian habitats during aging, disease, and future space habitation.
MeSH
Laboratories, Aging