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Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies

BACKGROUND: Elderly individuals have an eroded immune system but whether immune senescence is implicated with the development of frailty is unknown. The underlying immune mechanisms and the link between markers of senescence and physical frailty is not well established. METHODS: We explored the asso...

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Autores principales: Ng, Tze Pin, Camous, Xavier, Nyunt, Ma Shwe Zin, Vasudev, Anusha, Tan, Crystal Tze Ying, Feng, Liang, Fulop, Tamas, Yap, Keng Bee, Larbi, Anis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514983/
https://www.ncbi.nlm.nih.gov/pubmed/28721254
http://dx.doi.org/10.1038/npjamd.2015.5
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author Ng, Tze Pin
Camous, Xavier
Nyunt, Ma Shwe Zin
Vasudev, Anusha
Tan, Crystal Tze Ying
Feng, Liang
Fulop, Tamas
Yap, Keng Bee
Larbi, Anis
author_facet Ng, Tze Pin
Camous, Xavier
Nyunt, Ma Shwe Zin
Vasudev, Anusha
Tan, Crystal Tze Ying
Feng, Liang
Fulop, Tamas
Yap, Keng Bee
Larbi, Anis
author_sort Ng, Tze Pin
collection PubMed
description BACKGROUND: Elderly individuals have an eroded immune system but whether immune senescence is implicated with the development of frailty is unknown. The underlying immune mechanisms and the link between markers of senescence and physical frailty is not well established. METHODS: We explored the association of specific T-cell subset markers of immune differentiation and senescence on CD4(+) and CD8(+) cells (CD28(−), CD27(−) and CD57(+)) and the immune risk profile (inverted CD4/CD8 ratio <1) with physical frailty among 421 participants who were frail (N=32), prefrail (N=187) and robust (N=202) in the Singapore Longitudinal Ageing Study cohort. RESULTS: In ordinal logistic regression models relating tertile category rank scores of immune biomarker with frailty status (robust, prefrail and frail), CD8(+)CD28(−)CD27(+) (odds ratio (OR)=1.35, P=0.013), CD4(+)CD28(−)CD27(+) (OR=1.29, P=0.025), CD8(+)CD28(−) (OR=1.31, P=0.022), and CD4/CD8 ratio (OR=1.27, P=0.026) were positively associated with frailty, controlling for age, sex and multimorbidity. CD4/CD8 ratio less than one was not associated with frailty (OR=0.84, P=0.64). In stepwise multinomial logistic regression controlling for age, sex and comorbidity, only CD8(+)CD28(−)CD27(+) was the independent predictor of prefrailty: highest tertile of the immune marker significantly predicted prefrailty (versus low tertile, OR=1.72, P=0.037) and frailty (OR=2.56, P=0.06). CONCLUSION: The study supports the hypothetical role of immune senescence in physical frailty, particularly in regard to the observed loss of CD28 expression from both CD8(+) cells and CD4(+) cells, but not for CD27 or CD4/CD8 ratio as a marker of senescence. The potential of CD8(+)CD28(−)CD27(+) as a biological marker of frailty should be further investigated in prospective studies.
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spelling pubmed-55149832017-07-18 Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies Ng, Tze Pin Camous, Xavier Nyunt, Ma Shwe Zin Vasudev, Anusha Tan, Crystal Tze Ying Feng, Liang Fulop, Tamas Yap, Keng Bee Larbi, Anis NPJ Aging Mech Dis Article BACKGROUND: Elderly individuals have an eroded immune system but whether immune senescence is implicated with the development of frailty is unknown. The underlying immune mechanisms and the link between markers of senescence and physical frailty is not well established. METHODS: We explored the association of specific T-cell subset markers of immune differentiation and senescence on CD4(+) and CD8(+) cells (CD28(−), CD27(−) and CD57(+)) and the immune risk profile (inverted CD4/CD8 ratio <1) with physical frailty among 421 participants who were frail (N=32), prefrail (N=187) and robust (N=202) in the Singapore Longitudinal Ageing Study cohort. RESULTS: In ordinal logistic regression models relating tertile category rank scores of immune biomarker with frailty status (robust, prefrail and frail), CD8(+)CD28(−)CD27(+) (odds ratio (OR)=1.35, P=0.013), CD4(+)CD28(−)CD27(+) (OR=1.29, P=0.025), CD8(+)CD28(−) (OR=1.31, P=0.022), and CD4/CD8 ratio (OR=1.27, P=0.026) were positively associated with frailty, controlling for age, sex and multimorbidity. CD4/CD8 ratio less than one was not associated with frailty (OR=0.84, P=0.64). In stepwise multinomial logistic regression controlling for age, sex and comorbidity, only CD8(+)CD28(−)CD27(+) was the independent predictor of prefrailty: highest tertile of the immune marker significantly predicted prefrailty (versus low tertile, OR=1.72, P=0.037) and frailty (OR=2.56, P=0.06). CONCLUSION: The study supports the hypothetical role of immune senescence in physical frailty, particularly in regard to the observed loss of CD28 expression from both CD8(+) cells and CD4(+) cells, but not for CD27 or CD4/CD8 ratio as a marker of senescence. The potential of CD8(+)CD28(−)CD27(+) as a biological marker of frailty should be further investigated in prospective studies. Nature Publishing Group 2015-09-28 /pmc/articles/PMC5514983/ /pubmed/28721254 http://dx.doi.org/10.1038/npjamd.2015.5 Text en Copyright © 2015 Japanese Society of Anti-Aging Medicine/Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ng, Tze Pin
Camous, Xavier
Nyunt, Ma Shwe Zin
Vasudev, Anusha
Tan, Crystal Tze Ying
Feng, Liang
Fulop, Tamas
Yap, Keng Bee
Larbi, Anis
Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies
title Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies
title_full Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies
title_fullStr Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies
title_full_unstemmed Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies
title_short Markers of T-cell senescence and physical frailty: insights from Singapore Longitudinal Ageing Studies
title_sort markers of t-cell senescence and physical frailty: insights from singapore longitudinal ageing studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514983/
https://www.ncbi.nlm.nih.gov/pubmed/28721254
http://dx.doi.org/10.1038/npjamd.2015.5
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