@article {11926, title = {Age-related differences in T cell subsets in a nationally representative sample of people over age 55: Findings from the Health and Retirement Study.}, journal = {The Journals of Gerontology, Series A }, volume = {77}, year = {2022}, pages = {927-933}, abstract = {

Though T cell immunosenescence is a major risk factor for age-related diseases, susceptibility to infections, and responses to vaccines, differences in T cells subset counts and representation by age and sex have not been determined for a large sample representative of the national population of the US. We evaluated the counts of T cell subsets including total, CD4+ and CD8+ T cells, and their na{\"\i}ve (Tn), effector memory (Tem) and effector subsets, in the context of age, sex and exposure to cytomegalovirus (CMV) infection among 8,848 Health and Retirement Study (HRS) participants, a nationally representative study of adults over 55 years. Total T cells (CD3+) and CD4+ cells declined markedly with age; CD8+ T cells declined somewhat less. While CD4+ T cell declines with age occurred for both CMV seropositive and CMV seronegative groups, total T cells and CD8+ cells were both substantially higher among the CMV seropositive group. Numbers of Tn CD4+ and CD8+ cells were strongly and inversely related to age, were better conserved among women, and were independent of CMV seropositivity. By contrast, accumulation of the CD8+ and CD4+ Tem and effector subsets was CMV-associated. This is the first study to provide counts of T cell subsets by age and sex in a national sample of older US adults over the age of 55 years. Understanding T cell changes with age and sex is an important first step in determining strategies to reduce its impact on age-related diseases and susceptibility to infection.

}, keywords = {Aging, CMV Seropositivity}, issn = {1758-535X}, doi = {10.1093/gerona/glab300}, author = {Bharat Thyagarajan and Jessica Faul and Vivek, Sithara and Jung K Kim and Nikolich-{\v Z}ugich, Janko and David R Weir and Eileen M. Crimmins} } @article {12601, title = {A computational solution for bolstering reliability of epigenetic clocks: implications for clinical trials and longitudinal tracking}, journal = {Nature Aging}, volume = {2}, year = {2022}, pages = {644{\textendash}661}, abstract = {Epigenetic clocks are widely used aging biomarkers calculated from DNA methylation data, but this data can be surprisingly unreliable. Here we show that technical noise produces deviations up to 9 years between replicates for six prominent epigenetic clocks, limiting their utility. We present a computational solution to bolster reliability, calculating principal components (PCs) from CpG-level data as input for biological age prediction. Our retrained PC versions of six clocks show agreement between most replicates within 1.5 years, improved detection of clock associations and intervention effects, and reliable longitudinal trajectories in vivo and in vitro. This method entails only one additional step compared to traditional clocks, requires no replicates or previous knowledge of CpG reliabilities for training, and can be applied to any existing or future epigenetic biomarker. The high reliability of PC-based clocks is critical for applications to personalized medicine, longitudinal tracking, in vitro studies and clinical trials of aging interventions.}, keywords = {Aging, Bioinformatics, computational models, DNA Methylation, predictive markers}, doi = {10.1038/s43587-022-00248-2}, author = {Higgins-Chen, Albert T. and Thrush, Kyra L. and Wang, Yunzhang and Minteer, Christopher J. and Kuo, Pei-Lun and Wang, Meng and Niimi, Peter and Sturm, Gabriel and Lin, Jue and Ann Zenobia Moore and Bandinelli, Stefania and Vinkers, Christiaan H. and Vermetten, Eric and Rutten, Bart P. F. and Geuze, Elbert and Okhuijsen-Pfeifer, Cynthia and van der Horst, Marte and Schreiter, Stefanie and Gutwinski, Stefan and Luykx, Jurjen J. and Picard, Martin and Ferrucci, Luigi and Eileen M. Crimmins and Boks, Marco P. and H{\"a}gg, Sara and Hu-Seliger, Tina T. and Morgan E. Levine} } @article {11930, title = {Cross sectional association between cytomegalovirus seropositivity, inflammation and cognitive impairment in elderly cancer survivors.}, journal = {Cancer Causes \& Control}, volume = {33}, year = {2022}, pages = {81-90}, abstract = {

PURPOSE: The higher prevalence of cognitive impairment/ dementia among cancer survivors is likely multifactorial. Since both exposures to cytomegalovirus (CMV) and inflammation are common among elderly cancer survivors, we evaluated their contribution towards dementia.

METHODS: Data from 1387 cancer survivors and 7004 participants without cancer in the 2016 wave of the Health and Retirement Study (HRS) was used in this study. Two inflammatory biomarkers, C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR), were used to create an inflammation score. We used survey logistic regression adjusted for survey design parameters.

RESULTS: CMV seropositivity was not associated with cognitive impairment among cancer survivors (p = 0.2). In addition, inflammation was associated with elevated odds of cognitive impairment (OR = 2.2, 95\% CI [1.2, 4.2]). Cancer survivors who were both CMV seropositive and had increased inflammation had the highest odds of cognitive impairment compared to those who were CMV seronegative and had low inflammation (OR = 3.8, 95\% CI [1.5, 9.4]). The stratified analysis among cancer survivors showed this association was seen only among cancer survivors in whom the cancer was diagnosed within three years of measurement of inflammation score and CMV serostatus (OR = 18.5; 95\% CI [6.1, 56.1]).

CONCLUSION: The CMV seropositivity and high inflammation was associated with higher cognitive impairment among cancer survivors. The stronger associations seen among cancer survivors diagnosed within the last three years suggest that strategies to reduce CMV activation and inflammation during or immediately after cancer treatment may be important in reducing the prevalence of cognitive impairment/ dementia among cancer survivors.

}, keywords = {Cancer survivor, CMV Seropositivity, Dementia, Inflammation}, issn = {1573-7225}, doi = {https://doi.org/10.1007/s10552-021-01504-3}, author = {Vivek, Sithara and Heather Hammond Nelson and Anna Prizment and Jessica Faul and Eileen M. Crimmins and Bharat Thyagarajan} } @article {12568, title = {Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study.}, journal = {Immunity \& Ageing}, volume = {19}, year = {2022}, pages = {33}, abstract = {

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 na{\"\i}ve T-cells (T) and increase in memory T-cells (T). 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/(T (Central Memory) + T (Effector Memory) + T (Effector)) (referred as T/T) 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 and CD8 + T/T 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/T and CD4 + T~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/T and CD4 + T was inversely associated with multimorbidity. For CD4 + T/T, 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 subset were very similar to the associations seen with the CD4 + T/T. CD4 + T/T and CD4 + T 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/T and CD4 + T 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.

}, keywords = {Adaptive immunity, biological aging, immune aging, multimorbidity}, issn = {1742-4933}, doi = {10.1186/s12979-022-00290-z}, author = {Ramasubramanian, Ramya and Meier, Helen C S and Vivek, Sithara and Klopack, Eric and Eileen M. Crimmins and Jessica Faul and Nikolich-{\v Z}ugich, Janko and Bharat Thyagarajan} } @article {10426, title = {COMBINED EFFECT OF CMV SEROPOSITIVITY AND SYSTEMIC INFLAMMATION ON DEMENTIA PREVALENCE IN CANCER SURVIVORS}, journal = {Innovation in Aging}, volume = {3}, year = {2019}, pages = {S461-S461}, abstract = {Though cancer patients treated with multi-modal therapies demonstrate higher levels of systemic inflammation, which is associated with dementia, cancer survivors have not shown a consistent association with dementia. Since several studies reported an independent association between cytomegalovirus (CMV) infection, inflammation and dementia in non-cancer populations, we have evaluated whether CMV infection and systemic inflammation were associated with increased prevalence of dementia in cancer survivors in Health and Retirement Study (HRS). We evaluated prevalence of dementia (using score <=7 on the 27-point scale) among 1607 cancer survivors, in whom we measured CMV seropositivity and two biomarkers of systemic inflammation: C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR). The prevalence of CMV seropositivity was 68.26\% (n=1097), while prevalence of increased systemic inflammation [CRP \>5mg/L and NLR \>4] was 4.23\% (n=68). Using survey logistic regression, adjusted for age, race, gender, BMI (Body Mass Index) and sampling design, cancer survivors who were both CMV seropositive and had increased systemic inflammation had the highest odds of dementia compared to those who were CMV seronegative and had low levels of systemic inflammation (OR=6.59; 95\% CI [2.81, 15.44]; p\<.0001). Cancer survivors who were CMV seropositive without evidence of systemic inflammation had a lower but increased odds of dementia (OR=2.02; 95\% CI [1.17, 3.47]; p=0.01). Odds of dementia among those who were CMV seronegative with elevated systemic inflammation was not significant (p=0.09). Our study demonstrates a possible role for ongoing CMV induced inflammation in determining dementia prevalence among cancer survivors that needs further confirmation.}, keywords = {Cancer, cnv, Dementia, Inflammation, seropositivity}, issn = {2399-5300}, doi = {10.1093/geroni/igz038.1724}, author = {Vivek, Sithara and Bharat Thyagarajan and Heather Hammond Nelson and Anna Prizment and Eileen M. Crimmins and Jessica Faul} }