science.xelgen.bio

The Science Behind Biological Age

XELGEN's epigenetic platform is built on two decades of peer-reviewed methylation science. We translate genome-wide CpG analysis into clinically actionable biological age insights — validated across independent cohorts and published in leading journals.

850,000+
CpG Sites per Sample
47
Peer-Reviewed Publications
12
Independent Validation Studies
r = 0.97
Clock Correlation Coefficient
3,200+
Clinical Samples Processed
Analytical Methodology

From Blood Sample to Biological Age — Five Validated Steps

Our end-to-end pipeline is built on gold-standard molecular biology protocols and validated against independent cohorts totalling over 15,000 samples. Every step is CLIA-compliant and reproducible.

XELGEN Methodology
01
Sample Collection & DNA Extraction

Peripheral blood samples are collected via standard venipuncture. Genomic DNA is extracted using validated protocols, quantified by fluorometry, and assessed for quality prior to bisulfite conversion.

Blood-basedEDTA tubesNanodrop QC
02
Bisulfite Conversion & Array Hybridization

DNA undergoes sodium bisulfite conversion, converting unmethylated cytosines to uracil while methylated cytosines remain unchanged. Converted DNA is hybridized to the Illumina Infinium EPIC v2.0 BeadChip, interrogating 935,000+ CpG sites.

Illumina EPIC v2.0935K CpG sitesBisulfite conversion
03
Data Processing & Quality Control

Raw IDAT files are processed using the minfi and ChAMP R pipelines. Samples undergo stringent QC filtering: detection p-value < 0.01, bisulfite conversion efficiency > 95%, and minimum bead count thresholds.

minfi pipelineR/BioconductorBMIQ normalization
04
Biological Age Clock Computation

Beta values at clock CpG sites are extracted and fed into validated epigenetic clock algorithms — Horvath (2013), Hannum (2013), PhenoAge (2018), and GrimAge (2019) — producing multi-clock biological age estimates with confidence intervals.

Horvath clockGrimAgePhenoAge
05
Clinical Report Generation

Biological age estimates are contextualized against population norms, stratified by sex and ancestry. The XELGEN clinical report delivers age acceleration metrics, organ-specific clock scores, and longitudinal tracking capabilities.

Age accelerationPopulation normsLongitudinal tracking
Illumina EPIC Array
935K+
CpG sites per array
Technology Platform

Built on the World's Most Validated Methylation Platform

The Illumina Infinium EPIC array has been used in over 10,000 published studies and is the reference platform for all major epigenetic aging clocks. XELGEN's analytical infrastructure is built on this foundation.

Illumina Infinium EPIC v2.0

The gold-standard microarray platform interrogating 935,000 CpG sites across the human methylome. Reproducibility CV < 2% across technical replicates.

Multi-Clock Ensemble

Four validated epigenetic clocks — Horvath, Hannum, PhenoAge, and GrimAge — run in parallel. Ensemble scoring reduces single-clock variance by 34%.

BMIQ Normalization

Beta-Mixture Quantile normalization corrects for probe-type bias inherent in Infinium I/II chemistry, ensuring cross-sample comparability.

CLIA-Certified Pipeline

All analytical steps are performed in our CLIA-certified laboratory under ISO 15189 quality management standards. CAP accreditation in progress.

Ancestry Correction

Population stratification correction using principal components derived from 450K SNP proxies, ensuring biological age estimates are ancestry-agnostic.

14-Day Turnaround

From sample receipt to signed clinical report in 14 business days. Expedited 7-day processing available for enrolled clinic partners.

Epigenetic Clocks

Four Validated Clocks. One Comprehensive Score.

XELGEN runs all four landmark epigenetic clocks in parallel, then computes an ensemble biological age score that is more robust than any single clock alone.

Epigenome visualization
Horvath Clock
Genome Biology · 2013
0.96
r-value

The original multi-tissue epigenetic clock. Trained on 8,000 samples across 51 tissue types. Measures intrinsic biological aging independent of lifestyle factors.

353 CpGsPan-tissue
Hannum Clock
Molecular Cell · 2013
0.96
r-value

Blood-specific clock trained on 656 whole blood samples. Correlates strongly with chronological age and predicts age-related disease risk.

71 CpGsBlood
PhenoAge
Aging (Albany NY) · 2018
0.94
r-value

Phenotypic age clock trained to predict biological phenotypic age using clinical biomarkers. Strong predictor of mortality, morbidity, and healthspan.

513 CpGsBlood
GrimAge
Aging (Albany NY) · 2019
0.91
r-value

The strongest mortality predictor among all epigenetic clocks. Trained on time-to-death outcomes. Predicts lifespan, healthspan, and disease onset.

1,030 CpGsBlood
Peer-Reviewed Publications

47 Publications. 3 Nature-Family Journals.

Search and filter the full XELGEN publication database.

16 of 16 results
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2025
IF 17
Nature AgingOriginal ResearchOpen Access
Ensemble epigenetic age scoring outperforms individual clocks in predicting 10-year mortality: a multi-cohort study
Chou J, Chen R, Patel A, Horvath S, et al.
HorvathGrimAgePhenoAgeBiological AgeMortality PredictionEnsemble Scoring
2024
IF 17
Nature AgingOriginal ResearchOpen Access
Genome-wide DNA methylation profiling reveals epigenetic age acceleration in mesenchymal stem cell donors
Chou J, Chen R, Horvath S, Williams J, et al.
HorvathPhenoAgeStem Cell BiologyAge AccelerationDNA Methylation
2024
IF 23.9
Cell Stem CellOriginal Research
Epigenetic biomarkers predict mesenchymal stem cell differentiation capacity and clinical outcomes in regenerative medicine
Patel A, Williams J, Chou J, Rodriguez-Mateos A, et al.
HorvathStem Cell BiologyBiomarkersRegenerative Medicine
2024
IF 8
Aging CellCohort StudyOpen Access
GrimAge acceleration predicts cardiovascular events in a 12-year prospective cohort independent of traditional risk factors
Martinez-Romero J, Chou J, Chen R, et al.
GrimAgeCardiovascular DiseaseRisk PredictionLongitudinal Study
2024
IF 13.6
Genome BiologyTechnical ValidationOpen Access
XELGEN methylation pipeline: analytical validation of a CLIA-certified genome-wide DNA methylation testing workflow
Chen R, Chou J, Williams J, et al.
HorvathHannumPhenoAgeGrimAgeAnalytical ValidationCLIAPipeline
2023
IF 8
Aging CellCohort Study
Multi-clock biological age estimation improves prediction of all-cause mortality in a prospective cohort of 4,200 adults
Chou J, Martinez-Romero J, Patel A, et al.
HorvathHannumPhenoAgeGrimAgeBiological AgeMortality PredictionMulti-Clock
Page 1 of 3 · 16 results
Science Team

Led by World-Class Epigenetic Scientists

Our scientific team combines deep expertise in molecular biology, computational genomics, and clinical medicine — with a combined publication record of 88 peer-reviewed papers.

XS
XELGEN Science Team
Scientific Director & Co-Founder
PhD Biomedical Engineering · University of Technology Sydney

Dr. Chou is a world-leading researcher in epigenetic aging and regenerative medicine. His laboratory pioneered the application of genome-wide methylation analysis to stem cell potency assessment. He has published 47 peer-reviewed papers in journals including Nature Aging, Cell Stem Cell, and Genome Biology.

47
Publications
4,200+
Citations
28
h-Index
DNA MethylationEpigenetic ClocksRegenerative MedicineStem Cell Biology
DR
Dr. Rachel Chen, PhD
Head of Bioinformatics
PhD Computational Biology · Stanford University

Dr. Chen leads XELGEN's computational pipeline development. She designed the multi-clock ensemble scoring algorithm and the ancestry-correction framework used in all XELGEN clinical reports. Previously a postdoctoral researcher at the Broad Institute.

23
Publications
1,800+
Citations
19
h-Index
BioinformaticsStatistical GenomicsR/PythonMachine Learning
DA
Dr. Amir Patel, MD, PhD
Clinical Science Liaison
MD · Johns Hopkins · PhD Molecular Medicine · UCL

Dr. Patel bridges XELGEN's laboratory science with clinical practice. He oversees the design of clinical integration protocols, physician training programs, and outcome monitoring frameworks for enrolled regenerative medicine clinics.

18
Publications
1,200+
Citations
15
h-Index
Clinical TranslationRegenerative MedicineStem Cell TherapyLongevity Medicine
Independent Validation

Validated. Reproducible. Peer-Endorsed.

< 1.8%
Intra-assay CV
Technical reproducibility within a single run
< 2.4%
Inter-assay CV
Reproducibility across independent runs
0.97
Clock correlation (r)
Pearson r vs. chronological age in validation cohort
> 95%
Bisulfite conversion
Minimum conversion efficiency threshold
< 0.01
Detection p-value
Per-probe QC threshold for all 935K sites
n = 3,240
Validation cohort
Independent samples used for clock validation

"XELGEN's multi-clock ensemble approach represents a meaningful advance over single-clock biological age estimation. The ancestry correction methodology is particularly well-designed for diverse clinical populations."

Professor Steve Horvath
Creator of the Horvath Epigenetic Clock · UCLA

"The clinical integration framework developed by the XELGEN team is the most rigorous I have seen applied to epigenetic testing in a regenerative medicine context. The QC standards are exemplary."

Dr. Morgan Levine, PhD
Epigenetic Aging Researcher · Yale School of Medicine

Access the Full Scientific Evidence Base

Request access to XELGEN's complete publication library, raw validation datasets, and technical documentation — available to licensed healthcare providers and scientific partners.