TruAge + TruHealth Epigenetic Biological Age Panel (TruDiagnostic)

PCPhenoAge is a second-generation epigenetic biological age clock developed by Morgan Levine and colleagues, calibrated against clinical biomarker-defined phenotypic age rather than chronological age alone — making it more predictive of physiological status and disease risk than first-generation methylation clocks such as the Horvath pan-tissue clock. It is derived from principal-component analysis of DNA methylation patterns at a curated set of CpG sites, designed to capture the component of DNA methylation variability most informative for phenotypic ageing. DNA methylation — the addition of methyl groups to cytosine residues at CpG dinucleotides — is a stable epigenetic mark regulated by diet, environment, lifestyle, and biological ageing processes. The EPIC array platform used by TruDiagnostic quantifies methylation at approximately 850,000 CpG sites genome-wide.

PhenoAge is the most widely cited clinically relevant epigenetic biological age metric in the peer-reviewed longevity and preventive medicine literature and is independently associated with all-cause mortality, cardiovascular disease risk, cancer incidence, and multimorbidity in large prospective cohort studies. A PhenoAge below chronological age indicates biologically younger cellular function; acceleration above chronological age indicates an elevated physiological ageing burden that correlates with increased age-related disease risk. In functional and longevity medicine practice, serial PhenoAge measurement is used to track biological age trajectory and assess the impact of lifestyle, dietary, supplementation, and pharmacological longevity interventions over time.

GrimAge is a third-generation epigenetic clock developed by Steve Horvath and colleagues, trained on DNA methylation surrogates of plasma proteins (including GDF15, TIMP-1, PAI-1, ADM, leptin, and smoking-related proteins) alongside smoking pack-years, producing a composite biological age estimate optimised specifically for predicting time-to-death and age-related morbidity rather than chronological age. GrimAge is mechanistically distinct from PhenoAge — it captures methylation signatures of biological processes more directly linked to mortality pathways, including inflammatory and cardiovascular ageing trajectories. GrimAge2, the updated iteration, incorporates additional protein surrogates and demonstrates improved mortality prediction relative to the original version.

GrimAge and GrimAge acceleration (GrimAge − chronological age) are the most powerful epigenetic predictors of all-cause mortality and lifespan currently available in the peer-reviewed literature, outperforming first- and second-generation clocks in prospective mortality prediction. In longevity and preventive medicine practice, elevated GrimAge acceleration is interpreted as a signal of biological mortality risk that exceeds what would be expected from chronological age alone, motivating aggressive lifestyle and medical intervention. Smoking history is a particularly strong driver of GrimAge acceleration — the clock was partially trained on smoking methylation signatures and reflects cumulative tobacco exposure with high sensitivity.

DunedinPACE (Pace of Aging Computed from the Epigenome) is a longitudinal epigenetic measure developed from the Dunedin Study birth cohort, calibrated to reflect the rate of biological ageing — expressed as biological years elapsed per chronological year — rather than an absolute biological age point estimate. It was derived by tracking 19 longitudinal biomarkers of organ-system ageing across multiple time points in a single cohort and identifying the DNA methylation signature that most accurately predicted this composite ageing rate. Its key clinical advantage over age-point clocks is that it measures ageing velocity rather than accumulated ageing status — making it more sensitive to recent lifestyle and intervention changes and more actionable for monitoring the pace of biological change in real time.

DunedinPACE is increasingly used in longevity clinical practice as the most intervention-sensitive epigenetic ageing metric available, with published studies demonstrating response to caloric restriction, exercise, and other longevity interventions within months — a time frame shorter than that typically required for age-point clocks to show meaningful change. A DunedinPACE of 1.20 means a patient is biologically ageing at 1.20 years per chronological year — 20% faster than average — while 0.80 means 20% slower. Serial monitoring of DunedinPACE allows practitioners to assess whether interventions are meaningfully slowing the pace of ageing in an individual patient.

Telomeres are repetitive hexanucleotide (TTAGGG) sequences capping the ends of linear chromosomes, progressively shortened with each cell division due to the end-replication problem. Critically short telomeres trigger replicative senescence or apoptosis, contributing to tissue ageing and age-related disease. TruDiagnostic derives a telomere length estimate from DNA methylation patterns at telomere-associated CpG sites using a validated epigenetic proxy method rather than direct qPCR telomere length measurement. Epigenetic telomere length estimates correlate well with qPCR-based measurement but are not equivalent — they reflect the methylation signature associated with telomere length status rather than directly quantifying repeat copy number.

Telomere length is one of the hallmarks of cellular ageing and is associated with all-cause mortality, cardiovascular disease, and immune senescence in epidemiological studies. In longevity and functional medicine practice, telomere length is used as a complementary marker of biological ageing alongside epigenetic clock scores — short telomere length relative to age-matched peers supports an accelerated biological ageing interpretation. Telomere length is influenced by oxidative stress, chronic inflammation, psychological stress, smoking, and lifestyle factors — making it an actionable ageing marker responsive to targeted interventions.

DNA methylation-based immune cell deconvolution uses the cell-type-specific methylation signatures of different leucocyte populations — CD4+ T cells, CD8+ T cells, natural killer cells, B cells, monocytes, and granulocytes — to estimate the proportional composition of the peripheral blood immune cell landscape from a bulk blood DNA methylation sample. Age-related immune remodelling — termed immunosenescence — is characterised by a progressive shift toward decreased naïve T cells, increased exhausted effector memory CD8+ T cells, NK cell functional decline, and accumulation of senescent immune cells. These compositional changes are captured in the methylation signature and quantified as an epigenetic immune age estimate.

Immune ageing is a central driver of inflammaging — the chronic low-grade inflammatory state that accelerates age-related disease burden, reduces vaccine response, and impairs pathogen clearance. In functional medicine practice, an elevated immune age relative to chronological age contextualises inflammatory markers (hs-CRP, IL-6), immune function assessment, and vaccine response, and guides interventions targeting immune rejuvenation — including senolytic protocols, targeted nutrition, and exercise. The TruHealth immune age output situates the patient within the broader ageing landscape by revealing whether immune senescence is tracking ahead of or behind their overall biological age trajectory.

Second- and third-generation epigenetic research has demonstrated that different tissues and organ systems age at different biological rates within the same individual, producing organ-specific methylation clock signatures that can be estimated from blood DNA methylation using tissue-specific CpG models. Organs with accelerated epigenetic ageing relative to the individual's systemic clock age may be at disproportionate risk of organ-specific age-related pathology — a concept with direct clinical relevance for organ-targeted preventive medicine. These organ age estimates are derived computationally from blood methylation data using tissue-specific clock models and represent probabilistic estimates rather than direct tissue measurements.

Organ-specific epigenetic age scores provide a granular biological ageing map that guides targeted organ-level preventive interventions. A patient with an overall PhenoAge within normal range but an accelerated liver epigenetic age may benefit from liver-targeted intervention (dietary modification, alcohol reduction, NAFLD management) beyond what systemic clock scores would indicate. Similarly, accelerated cardiac epigenetic age alongside normal lipid parameters may provide earlier signal of cardiovascular biological risk. TruHealth organ age scores should be interpreted as risk indicators that complement conventional organ-function laboratory markers (liver enzymes, eGFR, echocardiography) rather than replace them.