Role of senescence marker p16INK4a measured in peripheral blood T-lymphocytes in predicting length of hospital stay after coronary artery bypass surgery in older adults

Adults older than 65 years undergo more than 120,000 coronary artery bypass (CAB) procedures each year in the United States. Chronological age alone, though commonly used in prediction models of outcomes after CAB, does not alone reflect variability in aging process; thus, the risk of complications in older adults. We performed a prospective study to evaluate a relationship between senescence marker p16INK4a expression in peripheral blood T-lymphocytes (p16 levels in PBTLs) with aging and with perioperative outcomes in older CAB patients. We included 55 patients age 55 and older, who underwent CAB in Johns Hopkins Hospital between September 1st, 2010 and March 25th, 2013. Demographic, clinical and laboratory data following outline of the Society of Thoracic Surgeons data collection form was collected, and p16 mRNA levels in PBTLs were measured using Taqman® qRT-PCR. Associations between p16 mRNA levels in PBTLs with length of hospital stay, frailty status, p16 protein levels in the aortic and left internal mammary artery tissue, cerebral oxygen saturation, and augmentation index as a measure of vascular stiffness were measured using regression analyses. Length of hospital stay was the primary outcome of interest, and major organ morbidity, mortality, and discharge to a skilled nursing facility were secondary outcomes. In secondary analysis, we evaluated associations between p16 mRNA levels in PBTLs and interleukin-6 levels using regression analyses. Median age of enrolled patients was 63.5 years (range 56-81 years), they were predominantly male (74.55%), of Caucasian descent (85.45%). Median log2(p16 levels in PBTLs) were 4.71 (range 1.10-6.82). P16 levels in PBTLs were significantly associated with chronological age (mean difference 0.06 for each year increase in age, 95% CI 0.01-0.11) and interleukin 6 levels (mean difference 0.09 for each pg/ml increase in IL-6 levels, 95% CI 0.01-0.18). There were no significant associations with frailty status, augmentation index, cerebral oxygenation and p16 protein levels in blood vessels. Increasing p16 levels in PBTLs did not predict length of stay in the hospital (HR 1.10, 95% CI 0.87-1.40) or intensive care unit (HR 1.02, 95% CI 0.79-1.32). Additional evaluation of p16 levels in PBTLs as predictor of perioperative outcomes is required and should include additional markers of immune system aging as well as different outcomes after CAB in addition to length of hospital stay

Interleukin-6 and C-Reactive Protein Levels and 9-Year Cognitive Decline in Community-Dwelling Older Women: The Women’s Health and Aging Study II

Elevated inflammation is a proposed mechanism relating chronic diseases to cognitive dysfunction. The objective of this study was to test the hypothesis that greater levels of inflammation, as measured by the proinflammatory cytokine interleukin-6 (IL-6) and C-reactive protein, are associated with faster rates of cognitive decline among cognitively intact community-dwelling older women

Health and function of participants in the Long Life Family Study: A comparison with other cohorts

Individuals from families recruited for the Long Life Family Study (LLFS) (n= 4559) were examined and compared to individuals from other cohorts to determine whether the recruitment targeting longevity resulted in a cohort of individuals with better health and function. Other cohorts with similar data included the Cardiovascular Health Study, the Framingham Heart Study, and the New England Centenarian Study. Diabetes, chronic pulmonary disease and peripheral artery disease tended to be less common in LLFS probands and offspring compared to similar aged persons in the other cohorts. Pulse pressure and triglycerides were lower, high density lipids were higher, and a perceptual speed task and gait speed were better in LLFS. Age-specific comparisons showed differences that would be consistent with a higher peak, later onset of decline or slower rate of change across age in LLFS participants. These findings suggest several priority phenotypes for inclusion in future genetic analysis to identify loci contributing to exceptional survival

Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients

Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18â question Center for Epidemiologic Studiesâ Depression Scale (CESâ D). Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CESâ D score > 14) and frailty were associated with KT length of stay (LOS), deathâ censored graft failure (DCGF), and mortality. At KT admission, 10.0% of patients exhibited depressive symptoms, 16.3% were frail, and 3.6% had both. Recipients with depressive symptoms were more likely to be frail (aOR = 3.97, 95% CI: 2.28â 6.91, P < 0.001). Recipients with both depressive symptoms and frailty had a 1.88 times (95% CI: 1.70â 2.08, P < 0.001) longer LOS, 6.20â fold (95% CI:1.67â 22.95, P < 0.01) increased risk of DCGF, and 2.62â fold (95% CI:1.03â 6.70, P = 0.04) increased risk of mortality, compared to those who were nonfrail and without depressive symptoms. There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction < 0.001). Interventions aimed at reducing preâ KT depressive symptoms and frailty should be explored for their impact on postâ KT outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146305/1/ctr13391_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146305/2/ctr13391.pd

Thyroid Autoantibodies Are Associated with a Reduced Prevalence of Frailty in Community-Dwelling Older Women

Context: The contribution of autoimmunity to the multisystem dysregulation that characterizes the frailty syndrome in older adults is unknown. Objective: The aim of the study was to investigate the relationship between thyroid antibodies and frailty in older women. Design, Setting, and Participants: We conducted a cross-sectional study nested within the Women’s Health and Aging Studies I and II. Thyroglobulin antibodies (TgAbs), thyroid peroxidase antibodies (TPOAbs), and antinuclear antibodies were measured in the baseline sera of 641 community-dwelling older women. Main Outcome Measure: Frailty was defined using a validated five-component measure. Results: The prevalence of prefrailty and frailty was lower in TgAb-positive than negative older women (37.1 vs. 47.8% and 6.7 vs.11.9%, respectively; P = 0.01 and 0.03). The prevalence of prefrailty, but not frailty, was lower in TPOAb-positive than negative women (38.9 vs. 48.0% and 10.1 vs. 11.3%; P = 0.04 and 0.34). After adjustment for covariates including serum thyroid stimulation hormone concentration and thyroid medication usage in multinomial regression models, TgAb-positive older women had lower odds of prefrailty and frailty compared with TgAb-negative women (odds ratio 0.57 and 0.30; 95% confidence interval 0.34–0.98 and 0.10–0.85, respectively). Similarly, TPOAb-positive older women had lower odds of frailty compared with TPOAb-negative women (odds ratio 0.44; 95% confidence interval 0.20–0.96). These trends were not observed with antinuclear antibodies. Conclusion: Independent of thyroid function status, community-dwelling older women who are seropositive for TgAbs and TPOAbs are less likely to be frail than seronegative women

Racial differences in inflammation and outcomes of aging among kidney transplant candidates

Abstract Background Inflammation is more common among African Americans (AAs), and it is associated with frailty, poor physical performance, and mortality in community-dwelling older adults. Given the elevated inflammation levels among end-stage renal disease (ESRD) patients, inflammation may be associated with adverse health outcomes such as frailty, physical impairment, and poor health-related quality of life (HRQOL), and these associations may differ between AA and non-AA ESRD patients. Methods One thousand three ESRD participants were recruited at kidney transplant evaluation (4/2014–5/2017), and inflammatory markers (interleukin-6 [IL-6], tumor necrosis factor-a receptor-1 [TNFR1], C-reactive protein [CRP]) were measured. We quantified the association with frailty (Fried phenotype), physical impairment (Short Physical Performance Battery [SPPB]), and fair/poor HRQOL at evaluation using adjusted modified Poisson regression and tested whether these associations differed by race (AA vs. non-AA). Results Non-AAs had lower levels of TNFR1 (9.7 ng/ml vs 14.0 ng/ml, p  0.9) and CRP (4.7 μg/ml vs 4.9 μg/ml, p = 0.4). Non-AAs had an increased risk of frailty with elevated IL-6 (RR = 1.58, 95% CI:1.27–1.96, p < 0.001), TNFR1 (RR = 1.60, 95% CI:1.25–2.05, p < 0.001), CRP (RR = 1.41, 95% CI:1.10–1.82, p < 0.01), and inflammatory index (RR = 1.82, 95% CI:1.44–2.31, p < 0.001). The associations between elevated inflammatory markers and frailty were not present among AAs. Similar results were seen with SPPB impairment and poor/fair HRQOL. Conclusions Non-AAs with elevated inflammatory markers may need closer follow-up and may benefit from prehabilitation to improve physical function, reduce frailty burden, and improve quality of life prior to transplant.https://deepblue.lib.umich.edu/bitstream/2027.42/149150/1/12882_2019_Article_1360.pd

Models and Studies of Aging: Executive Summary of a Report from the U13 Conference Series

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148241/1/jgs15788.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148241/2/jgs15780-sup-0001-supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148241/3/jgs15788_am.pd

Common Coding Variants of the HNF1A Gene Are Associated With Multiple Cardiovascular Risk Phenotypes in Community-Based Samples of Younger and Older European-American Adults: The Coronary Artery Risk Development in Young Adults Study and The Cardiovascular Health Study

The transcription factor hepatocyte nuclear factor 1 (HNF-1) α regulates the activity of a number of genes involved in innate immunity, blood coagulation, lipid and glucose transport and metabolism, and cellular detoxification. Common polymorphisms of the HNF-1α gene (HNF1A) were recently associated with plasma C-reactive protein (CRP) and gamma-glutamyl transferase (GGT) concentration in middle-aged to older European-Americans (EA)

Polymorphisms of the HNF1A Gene Encoding Hepatocyte Nuclear Factor-1α are Associated with C-Reactive Protein

Data from the Pharmacogenomics and Risk of Cardiovascular Disease (PARC) study and the Cardiovascular Health Study (CHS) provide independent and confirmatory evidence for association between common polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1α and plasma C-reactive protein (CRP) concentration. Analyses with the use of imputation-based methods to combine genotype data from both studies and to test untyped SNPs from the HapMap database identified several SNPs within a 5 kb region of HNF1A intron 1 with the strongest evidence of association with CRP phenotype