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Aging clocks

DNAmTL (DNA methylation telomere length)

DEDNAmTL (DNA-Methylierungs-Telomerlänge)

DNAmTL is an epigenetic estimate of your telomere length. It is derived from the methylation levels of 140 CpG sites in blood DNA. It was trained with elastic-net regression, against Southern-blot-measured leukocyte telomere length, in 2,256 participants from the Women's Health Initiative and Jackson Heart Study. Unlike qPCR or flow-FISH, it does not measure the telomere sequence directly. Instead, it captures a methylation signature that co-varies with telomere shortening, across the replicative history of your white blood cells. DNAmTL correlates with chronological age at r ≈ −0.62 to −0.80. That is much stronger than measured leukocyte telomere length (r ≈ −0.30 to −0.40). Lu, Horvath et al. (2019, Aging) validated it in 9,044 methylation arrays across seven cohorts, including Framingham and TwinsUK (mean follow-up 11.8 years). Each one-kilobase increase in age-adjusted DNAmTL came with a hazard ratio of 0.37 for all-cause death (p = 2.5×10⁻²⁰), 0.51 for coronary heart disease (p = 6.6×10⁻⁵), and 0.27 for congestive heart failure (p = 3.6×10⁻⁶). All were stronger than the measured-LTL associations. Wang et al. (2024, Clinical Epigenetics; NHANES 1999 to 2002) confirmed its edge over qPCR-based telomere length. Liang et al. (2024, Aging Cell; n = 2,398) showed a one-kilobase drop in DNAmTL goes with 40% higher death risk (HR = 0.60), and that HIV infection links to shorter DNAmTL (β = −0.25, p = 1.5×10⁻¹²). DNAmTL needs Illumina EPIC or 450k array data, and the causal direction is still unresolved.

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Sources

  1. Lu AT, Seeboth A, Tsai PC, Sun D, Quach A, Reiner AP, Kooperberg C, Ferrucci L, Hou L, Baccarelli AA, Li Y, Harris SE, Corley J, Taylor A, Deary IJ, Stewart JD, Whitsel EA, Assimes TL, Chen W, Li S, Mangino M, Bell JT, Wilson JG, Aviv A, Marioni RE, Raj K, Horvath S. (2019). DNA methylation-based estimator of telomere length. *Aging (Albany NY)*doi:10.18632/aging.102173
  2. Liang X, Aouizerat BE, So-Armah K, Cohen MH, Marconi VC, Xu K, Justice AC. (2024). DNA methylation-based telomere length is associated with HIV infection, physical frailty, cancer, and all-cause mortality. *Aging Cell*doi:10.1111/acel.14174
  3. Wang Q, Gao Y, Song J, Taiwaikuli D, Ding H, Yang X, Tang B, Zhou X. (2024). DNA methylation-based telomere length is more strongly associated with cardiovascular disease and long-term mortality than quantitative polymerase chain reaction-based telomere length: evidence from the NHANES 1999–2002. *Clinical Epigenetics*doi:10.1186/s13148-024-01795-8