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Telomere length and epigenetic clocks as markers of cellular aging: a comparative study

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Abstract

Telomere length (TL) and DNA methylation–based epigenetic clocks are markers of biological age, but the relationship between the two is not fully understood. Here, we used multivariable regression models to evaluate the relationships between leukocyte TL (LTL; measured by qPCR [n = 635] or flow FISH [n = 144]) and five epigenetic clocks (Hannum, DNAmAge pan-tissue, PhenoAge, SkinBlood, or GrimAge clocks), or their epigenetic age acceleration measures in healthy adults (age 19–61 years). LTL showed statistically significant negative correlations with all clocks (qPCR: r =  − 0.26 to − 0.32; flow FISH: r =  − 0.34 to − 0.49; p < 0.001 for all). Yet, models adjusted for age, sex, and race revealed significant associations between three of five clocks (PhenoAge, GrimAge, and Hannum clocks) and LTL by flow FISH (p < 0.01 for all) or qPCR (p < 0.001 for all). Significant associations between age acceleration measures for the same three clocks and qPCR or flow FISH TL were also found (p < 0.01 for all). Additionally, LTL (by qPCR or flow FISH) showed significant associations with extrinsic epigenetic age acceleration (EEAA: p < 0.0001 for both), but not intrinsic epigenetic age acceleration (IEAA; p > 0.05 for both). In conclusion, the relationships between LTL and epigenetic clocks were limited to clocks reflecting phenotypic age. The observed association between LTL and EEAA reflects the ability of both measures to detect immunosenescence. The observed modest correlations between LTL and epigenetic clocks highlight a possible benefit from incorporating both measures in understanding disease etiology and prognosis.

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Funding

This study was supported by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. The Cancer Genomics Research Laboratory is funded with Federal funds from the National Cancer Institute, National Institutes of Health, under NCI Contract No. 75N910D00024.

The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20–1-2705 and N00014-20–1-2832 from the Office of Naval Research. Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program.

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Authors and Affiliations

  1. Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Emily E. Pearce, Rotana Alsaggaf, Sharon A. Savage & Shahinaz M. Gadalla

  2. Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Shilpa Katta, Casey Dagnall & Belynda D. Hicks

  3. Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, USA

    Shilpa Katta, Casey Dagnall & Belynda D. Hicks

  4. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada

    Geraldine Aubert

  5. Center for International Blood and Marrow Transplant Research, Minneapolis, MN, 55401, USA

    Stephen R. Spellman

  6. Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA

    Steve Horvath

Authors
  1. Emily E. Pearce
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  2. Rotana Alsaggaf
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  4. Casey Dagnall
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  7. Stephen R. Spellman
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  8. Sharon A. Savage
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  9. Steve Horvath
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  10. Shahinaz M. Gadalla
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Contributions

Study design: Emily E. Pearce, Rotana Alsaggaf, and Shahinaz M. Gadalla. Sample acquisition: Stephen Spellman. Laboratory and bioinformatics: Geraldine Aubert, Casey L. Dagnall, Shilpa Katta, Steve Horvath, and Belynda Hicks. Statistical analysis: Emily E. Pearce and Rotana Alsaggaf. Data interpretation and manuscript drafting: Emily Pearce, Rotana Alsaggaf, Sharon Savage, and Shahinaz M. Gadalla. Manuscript critical review: all authors.

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Correspondence to Emily E. Pearce.

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Pearce, E.E., Alsaggaf, R., Katta, S. et al. Telomere length and epigenetic clocks as markers of cellular aging: a comparative study. GeroScience 44, 1861–1869 (2022). https://doi.org/10.1007/s11357-022-00586-4

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  • DOI: https://doi.org/10.1007/s11357-022-00586-4

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