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Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study
BACKGROUND: Cellular changes in adaptive immune system accompany the process of aging and contribute to an aging-related immune phenotype (ARIP) characterized by decrease in naïve T-cells (T(N)) and increase in memory T-cells (T(M)). A population-representative marker of ARIP and its associations wi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297609/ https://www.ncbi.nlm.nih.gov/pubmed/35858901 http://dx.doi.org/10.1186/s12979-022-00290-z |
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author | Ramasubramanian, Ramya Meier, Helen C. S. Vivek, Sithara Klopack, Eric Crimmins, Eileen M. Faul, Jessica Nikolich-Žugich, Janko Thyagarajan, Bharat |
author_facet | Ramasubramanian, Ramya Meier, Helen C. S. Vivek, Sithara Klopack, Eric Crimmins, Eileen M. Faul, Jessica Nikolich-Žugich, Janko Thyagarajan, Bharat |
author_sort | Ramasubramanian, Ramya |
collection | PubMed |
description | BACKGROUND: Cellular changes in adaptive immune system accompany the process of aging and contribute to an aging-related immune phenotype (ARIP) characterized by decrease in naïve T-cells (T(N)) and increase in memory T-cells (T(M)). A population-representative marker of ARIP and its associations with biological aging and age-related chronic conditions have not been studied previously. METHODS: We developed two ARIP indicators based on well understood age-related changes in T cell distribution: T(N)/(T(CM) (Central Memory) + T(EM) (Effector Memory) + T(EFF) (Effector)) (referred as T(N)/T(M)) in CD4 + and CD8 + T-cells. We compared them with existing ARIP measures including CD4/CD8 ratio and CD8 + TN cells by evaluating associations with chronological age and the Klemera Doubal measure of biological age (measured in years) using linear regression, multimorbidity using multinomial logistic regression and two-year mortality using logistic regression. RESULTS: CD8 + T(N) and CD8 + T(N)/T(M) had the strongest inverse association with chronological age (beta estimates: -3.41 and -3.61 respectively; p-value < 0.0001) after adjustment for sex, race/ethnicity and CMV status. CD4 + T(N)/T(M) and CD4 + T(N) had the strongest inverse association with biological age (β = -0.23; p = 0.003 and β = -0.24; p = 0.004 respectively) after adjustment for age, sex, race/ethnicity and CMV serostatus. CD4/CD8 ratio was not associated with chronological age or biological age. CD4 + T(N)/T(M) and CD4 + T(N) was inversely associated with multimorbidity. For CD4 + T(N)/T(M), people with 2 chronic conditions had an odds ratio of for 0.74 (95%CI: 0.63–0.86 p = 0.0003) compared to those without any chronic conditions while those with 3 chronic conditions had an odds ratio of 0.75 (95% CI: 0.63–0.90; p = 0.003) after adjustment for age, sex, race/ethnicity, CMV serostatus, smoking, and BMI. The results for the CD4 + T(N) subset were very similar to the associations seen with the CD4 + T(N)/T(M). CD4 + T(N)/T(M) and CD4 + T(N) were both associated with two-year mortality (OR = 0.80 (95% CI: 0.67–0.95; p = 0.01) and 0.81 (0.70–0.94; p = 0.01), respectively). CONCLUSION: CD4 + T(N)/T(M) and CD4 + T(N) had a stronger association with biological age, age-related morbidity and mortality compared to other ARIP measures. Future longitudinal studies are needed to evaluate the utility of the CD4 + subsets in predicting the risk of aging-related outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-022-00290-z. |
format | Online Article Text |
id | pubmed-9297609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-92976092022-07-21 Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study Ramasubramanian, Ramya Meier, Helen C. S. Vivek, Sithara Klopack, Eric Crimmins, Eileen M. Faul, Jessica Nikolich-Žugich, Janko Thyagarajan, Bharat Immun Ageing Research BACKGROUND: Cellular changes in adaptive immune system accompany the process of aging and contribute to an aging-related immune phenotype (ARIP) characterized by decrease in naïve T-cells (T(N)) and increase in memory T-cells (T(M)). A population-representative marker of ARIP and its associations with biological aging and age-related chronic conditions have not been studied previously. METHODS: We developed two ARIP indicators based on well understood age-related changes in T cell distribution: T(N)/(T(CM) (Central Memory) + T(EM) (Effector Memory) + T(EFF) (Effector)) (referred as T(N)/T(M)) in CD4 + and CD8 + T-cells. We compared them with existing ARIP measures including CD4/CD8 ratio and CD8 + TN cells by evaluating associations with chronological age and the Klemera Doubal measure of biological age (measured in years) using linear regression, multimorbidity using multinomial logistic regression and two-year mortality using logistic regression. RESULTS: CD8 + T(N) and CD8 + T(N)/T(M) had the strongest inverse association with chronological age (beta estimates: -3.41 and -3.61 respectively; p-value < 0.0001) after adjustment for sex, race/ethnicity and CMV status. CD4 + T(N)/T(M) and CD4 + T(N) had the strongest inverse association with biological age (β = -0.23; p = 0.003 and β = -0.24; p = 0.004 respectively) after adjustment for age, sex, race/ethnicity and CMV serostatus. CD4/CD8 ratio was not associated with chronological age or biological age. CD4 + T(N)/T(M) and CD4 + T(N) was inversely associated with multimorbidity. For CD4 + T(N)/T(M), people with 2 chronic conditions had an odds ratio of for 0.74 (95%CI: 0.63–0.86 p = 0.0003) compared to those without any chronic conditions while those with 3 chronic conditions had an odds ratio of 0.75 (95% CI: 0.63–0.90; p = 0.003) after adjustment for age, sex, race/ethnicity, CMV serostatus, smoking, and BMI. The results for the CD4 + T(N) subset were very similar to the associations seen with the CD4 + T(N)/T(M). CD4 + T(N)/T(M) and CD4 + T(N) were both associated with two-year mortality (OR = 0.80 (95% CI: 0.67–0.95; p = 0.01) and 0.81 (0.70–0.94; p = 0.01), respectively). CONCLUSION: CD4 + T(N)/T(M) and CD4 + T(N) had a stronger association with biological age, age-related morbidity and mortality compared to other ARIP measures. Future longitudinal studies are needed to evaluate the utility of the CD4 + subsets in predicting the risk of aging-related outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-022-00290-z. BioMed Central 2022-07-20 /pmc/articles/PMC9297609/ /pubmed/35858901 http://dx.doi.org/10.1186/s12979-022-00290-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Ramasubramanian, Ramya Meier, Helen C. S. Vivek, Sithara Klopack, Eric Crimmins, Eileen M. Faul, Jessica Nikolich-Žugich, Janko Thyagarajan, Bharat Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study |
title | Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study |
title_full | Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study |
title_fullStr | Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study |
title_full_unstemmed | Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study |
title_short | Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study |
title_sort | evaluation of t-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the health and retirement study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297609/ https://www.ncbi.nlm.nih.gov/pubmed/35858901 http://dx.doi.org/10.1186/s12979-022-00290-z |
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