Inflammatory and immune markers associated with physical frailty syndrome: findings from Singapore longitudinal aging studies.
Chronic systematic inflammation and reduced immune system fitness are considered potential contributing factors to the development of age-related frailty, but the underlying mechanisms are poorly defined. This exploratory study aimed to identify frailty-related inflammatory markers and immunological phenotypes in a cohort of community-dwelling adults aged ≥ 55 years. Frailty was assessed using two models, a Frailty Index and a categorical phenotype, and correlated with levels of circulating immune biomarkers and markers of senescence in immune cell subsets. We identified eight serological biomarkers that were associated with frailty, including sgp130, IL-2Rα, I-309, MCP-1, BCA-1, RANTES, leptin, and IL-6R. Frailty Index was inversely predicted by the frequency of CD3+, CD45RA+, and central memory CD4 cells, and positively predicted by the loss of CD28 expression, especially in CD8+ T cells, while frailty status was predicted by the frequency of terminal effector CD8+ T cells. In γ/δ T cells, frailty was negatively associated with CD27, and positively associated with IFNγ+TNFα- secretion by γ/δ2+ cells and IFNγ-TNFα+ secretion by γ/δ2- cells. Increased numbers of exhausted and CD38+ B cells, as well as CD14+CD16+ inflammatory monocytes, were also identified as frailty-associated phenotypes. This pilot study supports an association between inflammation, cellular immunity, and the process of frailty. These findings have significance for the early identification of frailty using circulating biomarkers prior to clinical manifestations of severe functional decline in the elderly.
Department of Clinical Psychology and Psychiatry/School of Public Health, Zhejiang University College of Medicine, Hangzhou, China.
Yanxia
Y
Lu
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Crystal Tze Ying
CT
Tan
Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Ma Shwe Zin
MS
Nyunt
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Esther Wing Hei
EW
Mok
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Xavier
X
Camous
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Hassen
H
Kared
Geriatrics Division, Department of Medicine, Research Center on Aging, University of Sherbrooke, Sherbrooke, Quebec, Canada.
Tamas
T
Fulop
Graduate Medical School, Duke-National University of Singapore, Singapore.
Liang
L
Feng
Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Tze Pin
TP
Ng
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.|Geriatrics Division, Department of Medicine, Research Center on Aging, University of Sherbrooke, Sherbrooke, Quebec, Canada.
Anis
A
Larbi
D000368:Aged; D000375:Aging / Q000276:immunology*; D005260:Female; D016330:Frail Elderly; D000073496:Frailty / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012846:Singapore
B cells; Gerotarget; T cell subsets; frailty risk; immunosenescence; inflammation