Association of Epigenetic Age and p16INK4a With Markers of T-Cell Composition in a Healthy Cohort
© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
How the measurement of aging biomarkers in peripheral blood T-lymphocytes (PBTLs) is influenced by cell composition is unclear. Here, we collected peripheral blood and isolated CD3+ PBTLs from 117 healthy couples between the ages of 21 and 72. Each sample was profiled for Horvath epigenetic clock (DNAm), p16INK4a expression, cytomegalovirus (CMV) seropositivity and 74 mRNA markers of PBTL subtype, differentiation, immune checkpoints, and cytokine production. Correlations between individual aging biomarkers (DNAm or p16INK4a) and PBTL mRNAs were corrected for chronological age, sex, and couple. DNAm measurements correlated with CMV seropositivity as well as PBTL mRNAs indicative of effector function (CD8A, EOMES, TBX21, GZMB), poor proliferative capacity (KLRG1, CD57), differentiation (CD45RO, CD45RA), and immune checkpoints (PDCD1, TIGIT, LAG3, CD160, CD244). In contrast, only three PBTL mRNAs, CD28, CD244, and p14ARF, showed a significant association with p16INK4a. p16INK4a expression also showed a weaker association with immunosenescent PBTL subsets than DNAm in flow cytometry analyses. These data suggest that PBTL composition has a greater influence on DNAm than p16INK4a and link accelerated epigenetic aging to immunosenescent phenotypes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:75 |
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| Enthalten in: |
The journals of gerontology. Series A, Biological sciences and medical sciences - 75(2020), 12 vom: 13. Nov., Seite 2299-2303 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Burd, Christin E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.02.2021 Date Revised 30.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/gerona/glaa108 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM309453321 |
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| 520 | |a © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a How the measurement of aging biomarkers in peripheral blood T-lymphocytes (PBTLs) is influenced by cell composition is unclear. Here, we collected peripheral blood and isolated CD3+ PBTLs from 117 healthy couples between the ages of 21 and 72. Each sample was profiled for Horvath epigenetic clock (DNAm), p16INK4a expression, cytomegalovirus (CMV) seropositivity and 74 mRNA markers of PBTL subtype, differentiation, immune checkpoints, and cytokine production. Correlations between individual aging biomarkers (DNAm or p16INK4a) and PBTL mRNAs were corrected for chronological age, sex, and couple. DNAm measurements correlated with CMV seropositivity as well as PBTL mRNAs indicative of effector function (CD8A, EOMES, TBX21, GZMB), poor proliferative capacity (KLRG1, CD57), differentiation (CD45RO, CD45RA), and immune checkpoints (PDCD1, TIGIT, LAG3, CD160, CD244). In contrast, only three PBTL mRNAs, CD28, CD244, and p14ARF, showed a significant association with p16INK4a. p16INK4a expression also showed a weaker association with immunosenescent PBTL subsets than DNAm in flow cytometry analyses. These data suggest that PBTL composition has a greater influence on DNAm than p16INK4a and link accelerated epigenetic aging to immunosenescent phenotypes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Aging biomarker | |
| 650 | 4 | |a CMV | |
| 650 | 4 | |a Horvath clock | |
| 650 | 4 | |a Senescence | |
| 650 | 4 | |a T cell | |
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| 650 | 7 | |a Genetic Markers |2 NLM | |
| 650 | 7 | |a Immune Checkpoint Proteins |2 NLM | |
| 700 | 1 | |a Peng, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Laskowski, Bryon F |e verfasserin |4 aut | |
| 700 | 1 | |a Hollyfield, Jennifer L |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Suohui |e verfasserin |4 aut | |
| 700 | 1 | |a Fadda, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Lianbo |e verfasserin |4 aut | |
| 700 | 1 | |a Andridge, Rebecca R |e verfasserin |4 aut | |
| 700 | 1 | |a Kiecolt-Glaser, Janice K |e verfasserin |4 aut | |
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