Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II)

Abstract Background Biological age reflects inter-individual differences in biological function and capacity beyond chronological age. DNA methylation age (DNAmA) and its deviation from chronological age, DNAmA acceleration (DNAmAA), which was calculated as residuals of leukocyte cell count adjusted...

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Main Authors: Valentin Max Vetter, Kamil Demircan, Jan Homann, Thilo Samson Chillon, Michael Mülleder, Orr Shomroni, Elisabeth Steinhagen-Thiessen, Markus Ralser, Christina M. Lill, Lars Bertram, Lutz Schomburg, Ilja Demuth
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Clinical Epigenetics
Online Access:https://doi.org/10.1186/s13148-025-01863-7
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author Valentin Max Vetter
Kamil Demircan
Jan Homann
Thilo Samson Chillon
Michael Mülleder
Orr Shomroni
Elisabeth Steinhagen-Thiessen
Markus Ralser
Christina M. Lill
Lars Bertram
Lutz Schomburg
Ilja Demuth
author_facet Valentin Max Vetter
Kamil Demircan
Jan Homann
Thilo Samson Chillon
Michael Mülleder
Orr Shomroni
Elisabeth Steinhagen-Thiessen
Markus Ralser
Christina M. Lill
Lars Bertram
Lutz Schomburg
Ilja Demuth
author_sort Valentin Max Vetter
collection DOAJ
description Abstract Background Biological age reflects inter-individual differences in biological function and capacity beyond chronological age. DNA methylation age (DNAmA) and its deviation from chronological age, DNAmA acceleration (DNAmAA), which was calculated as residuals of leukocyte cell count adjusted linear regression of DNAmA on chronological age, were used to estimate biological age in this study. Low levels of serum selenium, selenoprotein P (SELENOP), and the selenocysteine-containing glutathione peroxidase 3 (GPx3) are associated with adverse health outcomes and selenium supplementation is discussed as an anti-aging intervention. Methods In this study, we cross-sectionally analyzed 1568 older participants from the observational Berlin Aging Study II (mean age ± SD: 68.8 ± 3.7 years, 51% women). Serum selenium was measured by total reflection X-ray fluorescence (TXRF) spectroscopy and SELENOP was determined by sandwich ELISA. GPx3 was assessed as part of a proteomics dataset using liquid chromatography–mass spectrometry (LC–MS). The relationship between selenium biomarkers and epigenetic clock measures was analyzed using linear regression analyses. P values and 95% confidence intervals (not adjusted for multiple testing) are stated for each analysis. Results Participants with deficient serum selenium levels (< 90 μg/L) had a higher rate of biological aging (DunedinPACE, β = − 0.02, SE = 0.01, 95% CI − 0.033 to − 0.004, p = 0.010, n = 865). This association remained statistically significant after adjustment for age, sex, BMI, smoking, and first four genetic principal components (β = − 0.02, SE = 0.01, 95% CI − 0.034 to − 0.004, p = 0.012, n = 757). Compared to the highest quartile, participants in the lowest quartile of SELENOP levels showed an accelerated biological aging rate (DunedinPACE, β = − 0.03, SE = 0.01, 95% CI − 0.051 to − 0.008, p = 0.007, n = 740, fully adjusted model). Similarly, after adjustment for confounders, accelerated biological age was found in participants within the lowest GPx3 quartile compared to participants in the fourth quartile (DunedinPACE, β = − 0.04, SE = 0.01, 95% CI − 0.06 to − 0.02, p = 0.001, n = 674 and GrimAge, β = − 0.98, SE = 0.32, 95% CI − 1.6 to − 0.4, p = 0.002, n = 608). Only the association with GPx3 remained statistically significant after multiple testing correction. Conclusion Our study suggests that low levels of selenium biomarkers are associated with accelerated biological aging measured through epigenetic clocks. This effect was not substantially changed after adjustment for known confounders.
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spelling doaj-art-9fcd3cbf4e8f46afb669203f30b8dfb72025-08-20T03:53:31ZengBMCClinical Epigenetics1868-70832025-04-0117111210.1186/s13148-025-01863-7Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II)Valentin Max Vetter0Kamil Demircan1Jan Homann2Thilo Samson Chillon3Michael Mülleder4Orr Shomroni5Elisabeth Steinhagen-Thiessen6Markus Ralser7Christina M. Lill8Lars Bertram9Lutz Schomburg10Ilja Demuth11Department of Endocrinology and Metabolic Diseases (Including Division of Lipid Metabolism), Lipid Clinic at the Interdisciplinary Metabolism Center, Biology of Aging Working Group, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinMax Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinInstitute of Epidemiology and Social Medicine, University of MünsterMax Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinCore Facility High Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinCore Facility High Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Endocrinology and Metabolic Diseases (Including Division of Lipid Metabolism), Lipid Clinic at the Interdisciplinary Metabolism Center, Biology of Aging Working Group, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinCore Facility High Throughput Mass Spectrometry, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinInstitute of Epidemiology and Social Medicine, University of MünsterLübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of LübeckMax Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Endocrinology and Metabolic Diseases (Including Division of Lipid Metabolism), Lipid Clinic at the Interdisciplinary Metabolism Center, Biology of Aging Working Group, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinAbstract Background Biological age reflects inter-individual differences in biological function and capacity beyond chronological age. DNA methylation age (DNAmA) and its deviation from chronological age, DNAmA acceleration (DNAmAA), which was calculated as residuals of leukocyte cell count adjusted linear regression of DNAmA on chronological age, were used to estimate biological age in this study. Low levels of serum selenium, selenoprotein P (SELENOP), and the selenocysteine-containing glutathione peroxidase 3 (GPx3) are associated with adverse health outcomes and selenium supplementation is discussed as an anti-aging intervention. Methods In this study, we cross-sectionally analyzed 1568 older participants from the observational Berlin Aging Study II (mean age ± SD: 68.8 ± 3.7 years, 51% women). Serum selenium was measured by total reflection X-ray fluorescence (TXRF) spectroscopy and SELENOP was determined by sandwich ELISA. GPx3 was assessed as part of a proteomics dataset using liquid chromatography–mass spectrometry (LC–MS). The relationship between selenium biomarkers and epigenetic clock measures was analyzed using linear regression analyses. P values and 95% confidence intervals (not adjusted for multiple testing) are stated for each analysis. Results Participants with deficient serum selenium levels (< 90 μg/L) had a higher rate of biological aging (DunedinPACE, β = − 0.02, SE = 0.01, 95% CI − 0.033 to − 0.004, p = 0.010, n = 865). This association remained statistically significant after adjustment for age, sex, BMI, smoking, and first four genetic principal components (β = − 0.02, SE = 0.01, 95% CI − 0.034 to − 0.004, p = 0.012, n = 757). Compared to the highest quartile, participants in the lowest quartile of SELENOP levels showed an accelerated biological aging rate (DunedinPACE, β = − 0.03, SE = 0.01, 95% CI − 0.051 to − 0.008, p = 0.007, n = 740, fully adjusted model). Similarly, after adjustment for confounders, accelerated biological age was found in participants within the lowest GPx3 quartile compared to participants in the fourth quartile (DunedinPACE, β = − 0.04, SE = 0.01, 95% CI − 0.06 to − 0.02, p = 0.001, n = 674 and GrimAge, β = − 0.98, SE = 0.32, 95% CI − 1.6 to − 0.4, p = 0.002, n = 608). Only the association with GPx3 remained statistically significant after multiple testing correction. Conclusion Our study suggests that low levels of selenium biomarkers are associated with accelerated biological aging measured through epigenetic clocks. This effect was not substantially changed after adjustment for known confounders.https://doi.org/10.1186/s13148-025-01863-7
spellingShingle Valentin Max Vetter
Kamil Demircan
Jan Homann
Thilo Samson Chillon
Michael Mülleder
Orr Shomroni
Elisabeth Steinhagen-Thiessen
Markus Ralser
Christina M. Lill
Lars Bertram
Lutz Schomburg
Ilja Demuth
Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II)
Clinical Epigenetics
title Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II)
title_full Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II)
title_fullStr Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II)
title_full_unstemmed Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II)
title_short Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II)
title_sort low blood levels of selenium selenoprotein p and gpx3 are associated with accelerated biological aging results from the berlin aging study ii base ii
url https://doi.org/10.1186/s13148-025-01863-7
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