Table 1.
Summary of DNA methylation clocks
| Clock | Gen. | No. of CpGs | Age Range | Platform/Array | Method | Tissue | n | Model | Outcome | Ref. |
| DNAm-age | First | 3 | 18-70 | Illumina Infinium HumanMethylation 27K | Bisulphite conversion (EZ DNA Methylation Kit; Zymo) | Saliva | 68 | Lasso penalized regression | Association with chronological age | [85] |
| Epigenetic aging signature | First | 19 | 16-72 | Illumina Infinium HumanMethylation 27K | Used publicly available data - mixed | Mixed | 130 | Linear regression model | Association with chronological age | [88] |
| Passage Number | First | 6 | - | Illumina Infinium HumanMethylation 27K | Bisulphite conversion (EZ DNA Methylation Kit; Zymo) | Dermal fibroblasts &mesenchymal stem cells | 51 | Pavlidis Template Matching | Track passage number in fibroblast cell culture | [88] |
| EVOLV2 epigenetic marker of age | First | 1 | 9-99 | Illumina Infinium HumanMethylation 450K | Bisulphite conversion (EZ DNA Methylation Gold Kit; Zymo) | Blood | 501 | Spearman correlation | Association with chronological age | [147] |
| Florath age predictor | First | 17 | 50-75 | Illumina Infinium HumanMethylation 450K | Bisulphite conversion (EZ DNA Methylation Kit; Zymo) | Blood | 400 | Linear regression model | Association with chronological age | [148] |
| DNAm-age | First | 353 | 0-101 | Illumina Infinium HumanMethylation 27K &450K | Used publicly available data - mixed | Mixed | 8,000 | Elastic Net regression | Association with chronological age, age-related disease, all-cause mortality, cancer, neurodegenerative phenotypes | [83] |
| DNAm-age | First | 71 | 19-101 | Illumina Infinium HumanMethylation 450K | Bisulphite conversion | Blood | 656 | Elastic Net (combination of Lasso and ridge regression) | Association with chronological age and all-cause mortality | [101] |
| DNAm-age | First | 3 | 0-78 | Illumina Infinium HumanMethylation 27K &450K | EpiTect Bisulphite Kit; QIAGEN | Blood | 575 | Multivariate linear model | Association with chronological age, clinical/lifestyle factors, telomere length, related disease phenotypes | [149] |
| DNAm-age | First | 99 | 19-101 | Illumina Infinium HumanMethylation 27K &450K | EpiTect Bisulphite Kit; QIAGEN | Blood | 656 | Multivariate linear model | Association with chronological age, clinical/lifestyle factors, telomere length, related disease phenotypes | [149] |
| DNAm-age | First | 102 | 0-78 | Illumina Infinium HumanMethylation 27K &450K | EpiTect Bisulphite Kit; QIAGEN | Blood | 575 | Multivariate linear model | Association with chronological age, clinical/lifestyle factors, telomere length, related disease phenotypes | [149] |
| Huang age predictor | First | 5 | 9-75 | Pyrosequencing | EpiTect Bisulphite Kit; QIAGEN | Blood | 89 | Linear regression model | Association with chronological age – for forensic use | [90] |
| Zbiec-Piekarska age predictor | First | 5 | 2-75 | Pyrosequencing | EpiTect Bisulphite Kit; QIAGEN | Blood | 420 | Multivariate linear model | Association with chronological age – for forensic use | [89] |
| Buccal Cell Signature | First | 5 | 1-85 | Pyrosequencing | Bisulphite conversion (EZ DNA Methylation Kit; Zymo) | Buccal Cells | 55 | Multivariate linear model | Epigenetic age predictor | [150] |
| Cho Model 2 | First | 5 | 20-74 | Pyrosequencing | Bisulphite Conversion (EZ DNA Methylation - Lightning ™ Kit; Zymo) | Blood | 100 | Multivariate linear model | Association with chronological age | [151] |
| DNAm-age from Saliva | First | 7 | 18-65 | Illumina Infinium HumanMethylation 450K &SNaPshot | Bisulfite Conversion | Saliva | 54 | Linear regression model | Enabled age prediction in saliva with high accuracy | [152] |
| Skin and Blood | First | 391 | 0-94 | Illumina Infinium HumanMethylation 450K &EPIC | Used publicly available data - mixed | Mixed | 896 | Elastic Net regression | Prediction of age | [153] |
| Zhang age predictor | First | 514 | 2-104 | Illumina Infinium HumanMethylation 450K &EPIC | Used publicly available data - mixed | Blood and Saliva | 13,661 | Elastic Net | Association with chronological age | [86] |
| Zhang age predictor | First | 319,607 | 2-104 | Illumina Infinium HumanMethylation 450K &EPIC | Used publicly available data - mixed | Blood and Saliva | 13,661 | Best Linear Unbiased Prediction | Association with chronological age | [86] |
| PedBE Clock | First | 94 | 0-20 | Illumina Infinium HumanMethylation 450K &EPIC | Used publicly available data | Buccal epithelial cells | 1,721 | Elastic Net | Tool for measuring biological age in children | [154] |
| DNAm-age | First | 5 | 19-70 | SNaPShot | Bisulphite conversion (Imprint™ DNA Modification Kitl Sigma-Aldrich) | Blood, saliva, and buccal cells | 448 | Linear Regression | Age prediction | [155] |
| DNAm-age | First | 5 | 24-86 | Bisulphite PCR | Bisulphite conversion (EZ DNA Methylation Gold Kit; Zymo) | Blood | 51 | Linear Regression | Age prediction for forensic use in deceased individuals | [156] |
| Blood-Bone-Tooth Age Prediction Model | First | 43 | 1-94 | Sanger Sequencing | Bisulphite conversion (EZ DNA Methylation Gold Kit; Zymo) | Blood, bone, and tooth | 185 | Multivariate linear model | Age prediction for forensic use in alive and deceased individuals | [157] |
| PC Horvath 1 PC Horvath 2 PC Hannum PC PhenoAge PC GrimAge PC DNAmTL | Second | PCs trained on 78,464 CpGs | 0-105-0.3-10119-10121-10024-9224-92 | Illumina Infinium HumanMethylation 450K &EPIC &Elysium custom array | Used publicly available data - mixed | Mixed | 4,2978956564,5052,7542,754 | Principle components and elastic net regression | PC clocks show reduced technical noise allowing for improved detection of clock associations, intervention effects and reliable longitudinal tracking | [158] |
| Cortical DNAm Clock | Second | 347 | 1–104 | Illumina Infinium HumanMethylation 450K array | Used publicly available data - mixed | Human cortex | 1,397 | Elastic Net regression | Clock outperforms previously reported clocks | [138] |
| Boroni Skin | Second | 2,266 | 18–95 | Illumina Infinium HumanMethylation EPIC array | Used publicly available data | Human skin | 508 | Elastic Net regression | Skin specific DNAm age predictor | [159] |
| epiTOC | Second | 385 | 19–101 | Illumina Infinium HumanMethylation 450K array | Used publicly available data | Blood | 656 | Linear regression model | Association with mitotic age, cancer | [92] |
| Epigenetic age predictor | First | 99 | 0–78 | Illumin Infinium HumanMethylation 27k array | Lothian Birth Cohorts 1921 and 1936 | Blood | 575 | Cox linear regression | Association with life expectancy | [160] |
| Biological age predictor | First | 8 | – | Methylation-sensitive single-nucleotide primer extension (MS-SNuPE) | Used publicly available data - mixed | Blood | 390 | Multiple linear regression | Simplified assay for epigenetic age estimation | [161] |
| All-cause mortality | Second | 10 | 31–82 | Illumina Infinium HumanMethylation 450K array | Bisulphite conversion | Blood | 1,000 | Lasso penalized regression | Association with all-cause CVD, cancer, smoking behavior | [97] |
| MiAge | Second | 286 | – | Illumina Infinium HumanMethylation 450K array | Used publicly available data - mixed | 8 Cancer cell types | 4,020 | Linear regression model | Association with mitotic age, cancer outcome and survival prediction | [93] |
| DNAm PhenoAge | Second | 513 | >20 | Illumina Infinium HumanMethylation 27K, 450K &EPIC array | Used publicly available data - mixed | Blood | 9,926 | Cox penalized regression | Association with all cause and cause specific mortality, telomere length, survival, smoking status | [94] |
| DNAm GrimAge | Second | 1,030 | - | Illumina Infinium HumanMethylation 450K &EPIC array | Used publicly available data - mixed | Blood | 1,731 | Elastic Net, Cox regression | Association with morbidity and mortality, survival, cognitive decline, telomere length | [96] |
| DNAmTL | Second | 140 | 22-93 | Illumina Infinium HumanMethylation 450K &EPIC array | Used publicly available data - mixed | Blood | 2,256 | Multiple regression models | Association with chronological age, telomere length, morbidity and mortality, physical function | [95] |
| DunedinPoAm | Second | 140 | - | Illumina Infinium HumanMethylation 450K &EPIC array | Used publicly available data - mixed | Blood | 1,037 | Elastic Net | Blood DNAm measure sensitive to variation in pace of biological aging in individuals of same age | [98] |
| epiTOC2 | Second | 163 | 19-101 | Illumina Inifinium HumanMethylation 450K, Whole genome bisulfite sequencing, RNA-SeqV2 | Used publicly available data - mixed | Mixed | >2,000 | Formal dynamic model | Prediction of increased mitotic rate in cancer | [162] |
| Hypoclock | Second | - | - | Whole genome bisulfite sequencing, Illumina Inifinium HumanMethylation 450K | Used publicly available data - mixed | Mixed | - | Gaussian mixture model | DNA methylation loss in late-replicating domains linked to mitotic cell division | [163] |
| DunedinPACE | Second | 173 | Illumina Infinium HumanMethylation 450K &EPIC array | The Dunedin Study, the Understanding Society Study, the Normative Ageing Study, the Framingham Heart Study &the Environmental Risk Longitudinal Twin Study | Mixed | 1,037 | Elastic Net regression | Associated with morbidity, mortality, and disability. Novel blood biomarker of the age of pacing for gerontology and geroscience. | [164] | |
| GrimAge 2 | Second | 1,030 | Illumina Infinium HumanMethylation 450K &EPIC array | Used publicly available data - mixed | Mixed | 13,399 | Elastic Net, Cox regression | GrimAge 2 outperforms GrimAge and is an epigenetic biomarker of mortality and morbidity risk | [165] |