Organ-Specific Biomarkers of Aging: An Innovative Framework for Biological Age Assessment

Abstract: As population ages, there is an immense need to identify reliable biomarkers that reflect biological age, which is representative of the cumulative burden of physiological decline across all organ systems. The current model for estimating the systemic assessment of biological age relies on epigenetic and multiomic signatures, but there remains a gap in the literature regarding the modular assessment of organ-specific aging. We describe a conceptual and evidence-based framework for evaluating organ-specific aging biomarkers across major physiological systems and integrating them with systemic aging metrics to construct a holistic assessment of biological age. We reviewed and critically appraised emerging ageing biomarkers for the cardiovascular (e.g., VO₂ max, pulse wave velocity, ApoB), hepatic (e.g., ALT, GGT, elastography), renal (e.g., eGFR, cystatin C), pulmonary (e.g., FEV1), immune (e.g., hs-CRP, CD8:CD4 ratio), musculoskeletal (e.g., grip strength, DEXA-derived lean mass), neurocognitive (e.g., processing speed, MRI volumetrics), endocrine (e.g., DHEA-S, IGF-1, cortisol rhythm), and integumentary (e.g., dermal elasticity, wrinkle depth) systems. We evaluated these biomarkers and their relationship to the trajectory of age-related decline, response to interventions, and prognostic ability for morbidity, frailty, and mortality. The overall ageing trajectory can be estimated using a tiered model that integrates organ-level biomarkers with systemic DNA methylation indices (Horvath, GrimAge, DunedinPACE), blood-based aging calculators (PhenoAge, inflammaging indices), and functional aging metrics (e.g., gait speed, reaction time, sleep architecture). This work advocates for a modular yet integrated approach to biological age assessment that captures both organ-level and systemic aging signals. As longevity medicine and preventive geriatrics advance, such frameworks may support the development of personalized interventions to extend health span, improve clinical risk stratification, and facilitate early detection of organ-specific decline before the onset of overt disease. We emphasize the importance of validated outcome measures and caution against overreliance on unverified surrogate endpoints.

Keywords: Ageing, DNA Methylation, Organ specific biomarkers, biological age

DOI: 10.54941/ahfe1006967

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