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September 3, 2026Revista de investigaci�n Cl�nicaOpen Access

Biological aging clocks as biomarkers of human aging: Biological basis, methodological design, and epidemiological implications

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Authors

CFCarlos A. Fermín‐MartínezSGSara Berenice Garcia-GonzalezECElizabeth Garcia L. Castañeda

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Overview

Narrative review demonstrates that biological aging clocks capture distinct dimensions of human aging rather than a single construct, highlighting the need for mechanistic validation.

Key Points

  • Critically evaluate the biological foundations, statistical methodologies, interpretative challenges, and translational potential of biological aging clocks as biomarkers of human aging.
  • Synthesized molecular, multi-omics, and artificial intelligence-based frameworks underlying biological aging clocks across three distinct development generations.
  • Evaluated methodological and epidemiological challenges, including biological specificity, causal inference, confounding, reverse causation, and population generalizability.
  • Classified clocks into first-generation (trained on chronological age), second-generation (optimized for morbidity and mortality risk), and third-generation (measuring longitudinal pace of aging).
  • Identified that different biological aging clocks represent distinct physiological operationalizations of aging rather than interchangeable measures of a unified construct.
  • Highlighted key translational barriers, demonstrating that future clinical utility requires longitudinal validation across diverse cohorts to establish causal mechanisms.

Cite This Study

Fermín‐Martínez et al. (2026) studied this question.

synapsesocial.com/papers/6a9934ea636c6408cfa7cb91https://doi.org/10.1016/j.ric.2026.100053
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