TY - JOUR
T1 - Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study
AU - Ramasubramanian, Ramya
AU - Meier, Helen C.S.
AU - Vivek, Sithara
AU - Klopack, Eric
AU - Crimmins, Eileen M.
AU - Faul, Jessica
AU - Nikolich-Žugich, Janko
AU - Thyagarajan, Bharat
N1 - Funding Information:
This work was supported by the National Institute on Aging (NIA; R01 AG AG060110). The Health and Retirement Study is supported by NIA (U01 AG009740).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Adaptive immunity
KW - Biological aging
KW - Health and Retirement Study
KW - Immune aging
KW - Multimorbidity
UR - https://www.scopus.com/pages/publications/85134533526
UR - https://www.scopus.com/pages/publications/85134533526#tab=citedBy
U2 - 10.1186/s12979-022-00290-z
DO - 10.1186/s12979-022-00290-z
M3 - Article
C2 - 35858901
AN - SCOPUS:85134533526
SN - 1742-4933
VL - 19
JO - Immunity and Ageing
JF - Immunity and Ageing
IS - 1
M1 - 33
ER -