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

Tze Pin Ng,Anusha Vasudev,Keng Bee Yap,Ma Shwe Zin Nyunt,Crystal Tze Ying Tan,Liang Feng,Tamas Fulop,Anis Larbi,Xavier Camous

doi:10.1038/npjamd.2015.5

Abstract

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.

Highlights

Frailty is a geriatric syndrome which may be described as a nonspecific state of increased vulnerability resulting from decreased physiological reserves, multisystem dysregulation and limited capacity to maintain homeostasis.[1,2] Frail older persons are vulnerable to increased risk of hospitalization, dependency, institutionalization and deaths when exposed to stress
The data in this study support the hypothetical role of immune senescence in physical frailty, in regard to the observed loss of CD28 expression from CD8+ cells as well as CD4+ cells.[13,14]
Both subsets of CD8+CD28−CD27+ and CD4+CD28− CD27+ consistently showed a positive association with frailty

Summary

Introduction

Frailty is a geriatric syndrome which may be described as a nonspecific state of increased vulnerability resulting from decreased physiological reserves, multisystem dysregulation and limited capacity to maintain homeostasis.[1,2] Frail older persons are vulnerable to increased risk of hospitalization, dependency, institutionalization and deaths when exposed to stress. The age-associated loss of immunity known as immune senescence is strongly associated with higher vulnerability for severe infections,[5] vaccine failure[6] and premature mortality[7] in older individuals. These individuals are often considered as frail and at-risk for diseases. 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 o1) 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

Objectives

Methods

Results

Conclusion