The Association Between Cardiometabolic Risk and Cognitive Function Among Older Americans and Chinese.

BACKGROUND: Cardiometabolic risk (CMR) is associated with cognitive health, but the association can be affected by broader social, economic, and medical contexts. The United States and China have very different developmental and epidemiological histories, and thus CMR among older people could be linked to cognitive function differently in the 2 countries. METHODS: Cross-sectional and longitudinal ordinary least squares regression models were estimated for each country using nationally representative samples of populations over age 50: 7 430/4 474 Americans and 6 108/3 655 Chinese in the cross-sectional/longitudinal samples. RESULTS: In the United States, higher CMR is associated with worse cognitive function (b = -0.08, p < .016). Longitudinally, CMR increase is associated with worse cognitive function at a marginally significant level (b = -0.10, p = .055). No relationship between CMR level or change and cognitive function is observed in China. Higher education levels are linked to better cognitive function and slower cognitive decline in both countries. Unlike older Americans, relative to those with very low education levels, among older Chinese with the highest education level, a higher CMR links to better cognitive function (b = 0.63, p = .013) and slower cognitive decline (b = 0.35, p = .062); Nevertheless, a rapid increase in CMR is additionally harmful (b = -0.54, p = .050) for cognitive function and may lead to faster cognitive decline (b = -0.35, p = .079). CONCLUSIONS: The significant relationship between CMR and cognitive function in the United States suggests the importance of monitoring and controlling CMR factors at older ages. The insignificant relationship in China may be explained by the high CMR among those with high education levels, highlighting the need for improving cardiometabolic health through education and promoting healthy lifestyles.

The embodiment of parental death in early life through accelerated epigenetic aging: Implications for understanding how parental death before 18 shapes age-related health risk among older adults.

Parental death in early life has been linked to various adverse health outcomes in older adulthood. This study extends prior research to evaluate how parental death in early life is tied to accelerated epigenetic aging, a potentially important biological mechanism from which social and environmental exposures impact age-related health. We used data from the 2016 Venous Blood Study (VBS), a component of the Health and Retirement Study (HRS), to examine the association between parental death in early life and accelerated epigenetic aging as measured by three widely used epigenetic clocks (PCPhenoAge, PCGrimAge, and DunedinPACE). We also assessed whether some of the association is explained by differences in educational attainment, depressive symptoms, and smoking behavior. Methods included a series of linear regression models and formal mediation analysis. Findings indicated that parental death in early life is associated with accelerated epigenetic aging for PCPhenoAge and DunedinPACE. The inclusion of educational attainment, depressive symptoms, and smoking behavior attenuated this association, with formal mediation analysis providing additional support for these observations. Parental death in early life may be one of the most difficult experiences an individual may face. The elevated biological risk associated with parental death in early life may operate through immediate changes but also through more downstream risk factors. This study highlights how early life adversity can set in motion biological changes that have lifelong consequences.

Functional limitation among middle age and older adults: Exploring cross-national gender disparities.

OBJECTIVE: Functional limitations are prevalent among aging demographics, especially women. Structural and health factors, which vary worldwide, influence rates of functional limitations. Yet, gender disparities in functional limitation remain unclear in a global context. METHODS: We use 2018 data from the Health and Retirement Study (HRS) international family of studies with respondents ages 50-64 and (n = 87,479) and 65-89 (n = 92,145) to investigate gender disparities in large muscle functional limitation (LMFL) across 10 countries/regions using mixed effects logistic regression, with special attention to structural indicators of inequality and health. RESULTS: Among both women and men, LMFL was generally higher in China, India, Mexico, United States, and Baltic States than in England, Scandinavia, Southern Europe, Eastern Europe, and Western Europe. The gender disparity in LMFL gradually declined at older ages in India, China, Mexico, and United States, while this disparity gradually increased at older ages throughout Europe. Among middle age respondents, the greater risk of LMFL for women in countries/regions with a high GII was no longer observed after accounting for comorbidities. Among older respondents, a lower risk of LMFL for women in countries/regions with a high GII was not observed until accounting for comorbidities. DISCUSSION: Our findings suggest that rates of LMFL are higher in middle-income countries than high-income countries, especially among women, and in countries with a higher GII. In addition, consideration of comorbidities was integral to these relationships. Thus, national/regional contexts inform differential rates of functional limitation, particularly as it relates to gender.

Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk.

In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from  a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.

Association between hearing aid use and mortality in adults with hearing loss in the USA: a mortality follow-up study of a cross-sectional cohort.

BACKGROUND: Hearing loss has been identified as an independent risk factor for negative health outcomes and mortality. However, whether rehabilitation with hearing aid use is associated with lower mortality is currently unknown. This study aimed to examine the associations of hearing loss, hearing aid use, and mortality in the USA. METHODS: In this cross-sectional, follow-up study, we assessed 9885 adults (age 20 years and older) who participated in the National Health and Nutrition Examination Survey between 1999 and 2012 and completed audiometry and hearing aid use questionnaires (1863 adults with hearing loss). Main measures included hearing loss (speech-frequency pure-tone average) and hearing aid use (never users, non-regular users, and regular users). Mortality status of the cohort was linked to the National Death Index up to Dec 31, 2019. Cox proportional regression models were used to examine the association between hearing loss, hearing aid use, and mortality while adjusting for demographics and medical history. FINDINGS: The cohort consisted of 9885 participants, of which 5037 (51·0%) were female and 4848 (49·0%) were male with a mean age of 48·6 years (SD 18·1) at baseline. The weighted prevalence of audiometry-measured hearing loss was 14·7% (95% CI 13·3-16·3%) and the all-cause mortality rate was 13·2% (12·1-14·4) at a median 10·4 years of follow-up (range 0·1-20·8). The rate of regular hearing aid use among adults with hearing loss was 12·7% (95% CI 10·6-15·1). Hearing loss was an independent risk factor associated with higher mortality (adjusted hazard ratio [HR] 1·40 [95% CI 1·21-1·62]). Among individuals with hearing loss, the adjusted mortality risk was lower among regular hearing aid users in comparison with never users (adjusted HR 0·76 [0·60-0·95]) accounting for demographics, hearing levels, and medical history. There was no difference in adjusted mortality between non-regular hearing aid users and never users (adjusted HR 0·93 [0·70-1·24]). INTERPRETATION: Regular hearing aid use was associated with lower risks of mortality than in never users in US adults with hearing loss when accounting for age, hearing loss, and other potential confounders. Future research is needed to investigate the potential protective role of hearing aid use against mortality for adults with hearing loss. FUNDING: None.

Racial and Ethnic Differences in the Population-Attributable Fractions of Alzheimer Disease and Related Dementias.

BACKGROUND AND OBJECTIVES: Previous studies estimated that modifiable risk factors explain up to 40% of the dementia cases in the United States and that this population-attributable fraction (PAF) differs by race and ethnicity-estimates of future impact based on the risk factor prevalence in contemporary surveys. The aim of this study was to determine the race-specific and ethnicity-specific PAF of late-onset Alzheimer disease and related dementias (ADRDs) based on the risk factor prevalence and associations observed on the same individuals within a prospective cohort. METHODS: Data were from Multiethnic Cohort Study participants (African American, Japanese American, Latino, Native Hawaiian, and White) enrolled in Medicare Fee-for-Service. We estimated the PAF based on the prevalence of risk factors at cohort baseline and their mutually adjusted association with subsequent ADRD incidence. Risk factors included low educational attainment and midlife exposures to low neighborhood socioeconomic status, unmarried status, history of hypertension, stroke, diabetes or heart disease, smoking, physical inactivity, short or long sleep duration, obesity, and low-quality diet, as well as APOE ε4 for a subset. RESULTS: Among 91,881 participants (mean age 59.3 at baseline, 55.0% female participants), 16,507 incident ADRD cases were identified from Medicare claims (1999-2016, mean follow-up 9.3 years). The PAF for nongenetic factors combined was similar in men (24.0% [95% CI 21.3-26.6]) and women (22.8% [20.3-25.2]) but varied across Japanese American (14.2% [11.1-17.2]), White (21.9% [19.0-24.7]), African American (27.8% [22.3-33.0]), Native Hawaiian (29.3% [21.0-36.7]), and Latino (33.3% [27.5-38.5]) groups. The combined PAF was attenuated when accounting for competing risk of death, in both men (10.4%) and women (13.9%) and across racial and ethnic groups (4.7%-25.5%). The combined PAF was also different by age at diagnosis and ADRD subtypes, higher for younger (65-74 years: 43.2%) than older (75-84 years: 32.4%; ≥85 years: 11.3%) diagnoses and higher for vascular or unspecified ADRD than for AD or Lewy body dementia. An additional PAF of 11.8% (9.9-13.6) was associated with APOE ε4, which together with nongenetic risk factors accounted for 30.6% (25.8-35.1) of ADRD. DISCUSSION: Known risk factors explained about a third of the ADRD cases but with unequal distributions across racial and ethnic groups.

A naturally occurring variant of SHLP2 is a protective factor in Parkinson's disease.

Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate the functional role of a PD-associated mtSNP that impacts the mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.2158 T > C, a mtSNP associated with reduced PD risk, within the small open reading frame encoding SHLP2. This mtSNP results in an alternative form of SHLP2 (lysine 4 replaced with arginine; K4R). Using targeted mass spectrometry, we detect specific tryptic fragments of SHLP2 in neuronal cells and demonstrate its binding to mitochondrial complex 1. Notably, we observe that the K4R variant, associated with reduced PD risk, exhibits increased stability compared to WT SHLP2. Additionally, both WT and K4R SHLP2 show enhanced protection against mitochondrial dysfunction in in vitro experiments and confer protection against a PD-inducing toxin, a mitochondrial complex 1 inhibitor, in a mouse model. This study sheds light on the functional consequences of the m.2158 T > C mtSNP on SHLP2 and provides insights into the potential mechanisms by which this mtSNP may reduce the risk of PD.

Dried blood spot based biomarkers in the Health and Retirement Study: 2006 to 2016.

INTRODUCTION: The Health and Retirement Study (HRS) has collected biomarker data over multiple waves. Such data can help improve our understanding of health changes in individuals and the causal pathways related to health. There are, however, technical challenges to using the HRS dried blood spots (DBS) biomarker data due to changes over time in assay protocols, platforms, and laboratories. We provide technical and summary information on biological indicators collected as part of the HRS from 2006 to 2016 that should be helpful to users of the data. METHODS: We describe the opportunities and challenges provided by the HRS DBS data as well as insights provided by the data. The HRS collected DBS from its nationally representative sample of respondents 51 years of age or older from 2006 to 2016. DBS-based biomarkers were collected from half the sample in 2006, 2010, and 2014, and from the other half of the sample in 2008, 2012, and 2016. These DBS specimens were used to assay total and HDL cholesterol, glycosylated hemoglobin, C-reactive protein, and cystatin C from 2006 to 2016, and Interleukin 6 was added in 2014/2016. Samples included approximately 6000 individuals at each wave, and completion rates ranged from 81% to 90%. HRS transformed DBS values into venous blood equivalents to make them more comparable to those of the whole blood-based assays collected in most other studies and to facilitate longitudinal analysis. RESULTS: Distribution of changes over time by age shows that total cholesterol levels decreased for each age, while HbA1c levels increased. Cystatin C shows a clear age gradient, but a number of other markers do not. Non-Hispanic Black persons and Hispanic respondents have a higher incidence of risk levels of each biomarker except for CRP among non-Hispanic Black older persons. CONCLUSION: These public-use DBS data provide analysis opportunities that can be used to improve our understanding of health change with age in both populations and among individuals.

Pain, Physical Demands at Work, and Future Work Expectations Among Older Adults in the United States.

Background and Objectives: In the United States, pain is becoming increasingly prevalent among older adults at the same time as policies are incentivizing work longer. Given that pain and physically demanding jobs are both linked to early retirement and they often go hand-in-hand, it is important to assess how the unique effects of pain and physical work demands may interact in predicting future work expectations. Research Design and Methods: Using Health and Retirement Study data (1998, 2004, 2010, and 2016 waves), we assess how pain and physical job demands influence future work expectations of 10,358 adults at midlife (ages 51-56), after accounting for sociodemographic, job, health, and financial characteristics. Results: Compared to men with no pain, activity-interfering pain was associated with low expectations of full-time work past 62 regardless of job demands, while noninterfering pain was associated with 62% higher odds (odds ratio [OR] = 1.62, 95% confidence interval [CI]: 1.35-1.93) of expecting not to work full-time past age 62 only among those with physically demanding jobs. Having both interfering pain and a physically demanding job was associated with increased odds of expecting not to work full-time past age 65 for men (OR = 1.25, 95% CI: 1.06-1.47) and past age 62 for women (OR = 1.18, 95% CI: 1.00-1.39). Discussion and Implications: The co-occurrence of physically demanding work with pain-particularly activity-interfering pain-is associated with low expectations of full-time work past ages 62 and 65 for adults at midlife. Working longer may be feasible for older adults whose pain does not interfere with work, but unrealistic for individuals facing both pain and physically demanding work.

Harmonization of four biomarkers across nine nationally representative studies of older persons.

INTRODUCTION: A growing number of international population surveys have included measurement of biomarkers, but differ in the type of specimens collected, sample processing procedures, shipment protocols, and laboratory assay platforms. The purpose of this study is to harmonize biomarker data from nine nationally representative studies of people 50 years of age and over by adjusting for assay platforms and type of specimens for total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), glycosylated hemoglobin (HbA1c), and C-reactive protein (CRP). METHODS: Sets of 24 identical serum, plasma, whole blood, and dried blood spot harmonization samples with known analyte levels were generated at a reference laboratory, shipped at -80°C to the respective study laboratories, and subsequently assayed following the study laboratory's protocol. Both original and harmonized study data were used to calculate mean values and at-risk prevalence. RESULTS: The correlation coefficients between the biomarker values of the harmonization samples obtained by the study laboratories and the reference laboratory were 0.99 or above for all analytes and laboratories, indicating the high quality of assays at all laboratories. However, using the harmonized data from each study, there were significant differences in the mean values and country ranking of the prevalence of at-risk levels of these four biomarkers. CONCLUSIONS: While the biomarker data from the different study laboratories were highly correlated, indicating very high correlation of rank order of specimens, absolute values did vary significantly. This can have a major impact on assessment of international differences in estimates of risks for chronic morbidity and mortality.

Immune cells are associated with mortality: the Health and Retirement Study.

Introduction: Age-related immunosenescence is characterized by changes in immune cell subsets and is associated with mortality. However, since immunosenescence is associated with other concurrent age-related changes such as inflammation and multi-organ dysfunction, it is unclear whether the association between age-related immunosenescence and mortality is independent of other concurrent age-related changes. To address these limitations, we evaluated the independent association between immune cell subsets and mortality after adjustment for age-related inflammation and biologic age. Methods: Data for this study was obtained from the 2016 interview of the Health and Retirement Study (N=6802). Cox proportional hazards regression models were used to estimate the association between 25 immune cell subsets (11 T-cell subsets, 4 B-cell subsets, 3 monocyte subsets, 3 natural killer cell subsets, 3 dendritic cell subsets, and neutrophils) and 4-year mortality adjusting for covariates such as the Klemera-Doubal algorithm biological age, chronological age, gender, race/ethnicity, BMI, smoking status, comorbidity index, CMV seropositivity, and inflammatory latent variable comprising C-reactive protein, and 4 cytokines (interleukin-10, interleukin-1 receptor antagonist, interleukin-6, and soluble tumor necrosis factor). Results: Four hundred and seventy-six participants died during the study period with an overall median follow up time of 2.5 years. After controlling for covariates and adjustment for sample-weights, total T cells [HR: 0.86, p=0.004], NK CD56LO cells [HR: 0.88, p=0.005], and neutrophils [HR: 1.22, p=0.004] were significantly associated with mortality. Conclusions: These findings support the idea that an aging immune system is associated with short-term mortality independent of age-related inflammation or other age-related measures of physiological dysfunction. If replicated in other external cohorts, these findings could identify novel targets for both monitoring and intervention to reduce the age-related mortality.

Shingles Vaccine Uptake Among Older Adults: Identifying Early, Later, and Nonadopters.

Introduction: There is growing interest in accelerating adoptions of vaccines. This study examined factors that differentiate the acceptance and timing of uptake of the first shingles vaccine, Zostavax, among older adults in the U.S. Methods: Data from Health and Retirement Study respondents who were aged ≥62 years in 2008 were analyzed to determine whether they received a shingles vaccination from 2006 to 2016. Multinomial logistic regression was used to examine the characteristics associated with vaccine uptake and timing. Results: Of those eligible, 15.2% were vaccinated early (between 2006 and 2010), 20.2% were vaccinated later, and 64.6% remained unvaccinated 10 years after the shingles vaccine was introduced. Respondents more likely to be vaccinated were those who had higher education and income, experience with influenza vaccination, more frequent social interaction with friends, or were residing in an area with higher shingles vaccination rates. Conclusions: Shingles vaccination rates vary by social and geographic characteristics. Efforts to improve and expedite vaccination and other new preventive measures should target specific populations and geographic areas.

Exposure to the Indian Ocean Tsunami shapes the HPA-axis resulting in HPA "burnout" 14 years later.

Despite significant research on the effects of stress on the hypothalamic-pituitary-adrenal (HPA) axis, questions remain regarding long-term impacts of large-scale stressors. Leveraging data on exposure to an unanticipated major natural disaster, the 2004 Indian Ocean tsunami, we provide causal evidence of its imprint on hair cortisol levels fourteen years later. Data are drawn from the Study of the Tsunami Aftermath and Recovery, a population-representative longitudinal study of tsunami survivors who were living along the coast of Aceh, Indonesia, when the tsunami hit. Annual rounds of data, collected before, the year after and 2 y after the disaster provide detailed information about tsunami exposures and self-reported symptoms of post-traumatic stress. Hair samples collected 14 y after the tsunami from a sample of adult participants provide measures of cortisol levels, integrated over several months. Hair cortisol concentrations are substantially and significantly lower among females who were living, at the time of the tsunami, in communities directly damaged by the tsunami, in comparison with similar females living in other, nearby communities. Differences among males are small and not significant. Cortisol concentrations are lowest among those females living in damaged communities who reported elevated post-traumatic stress symptoms persistently for two years after the tsunami, indicating that the negative effects of exposure were largest for them. Low cortisol is also associated with contemporaneous reports of poor self-rated general and psychosocial health. Taken together, the evidence points to dysregulation in the HPA axis and "burnout" among these females fourteen years after exposure to the disaster.

Housing and Cardiometabolic Risk Among Older Renters and Homeowners.

Scholars consistently find that renters have poorer health outcomes when compared with homeowners. Health disparities between renters and homeowners likely widen over the life course, yet few studies have examined this link among older adults, and the connection is not fully understood. Homeowners' relative socioeconomic advantage may explain their better health; renters also more commonly experience adverse housing conditions and financial challenges, both of which can harm health. In this paper, we analyze the extent to which socioeconomic advantage, housing conditions, and financial strain explain the relationship between homeownership and health among adults over age 50, using Health and Retirement Study 2010/2012 data to assess cardiometabolic risk levels using biomarkers for inflammation, cardiovascular health, and metabolic function. We find that people living with poor housing conditions and financial strain have higher cardiometabolic risk levels, even taking socioeconomic advantage into account. This analysis sheds light on the housing-related health challenges of older adults, especially older renters.

Social relationships and epigenetic aging in older adulthood: Results from the Health and Retirement Study.

Growing evidence suggests that social relationship quality can influence age-related health outcomes, although how the quality of one's relationships directly relates to the underlying aging process is less clear. We hypothesized that the absence of close relationships as well as lower support and higher strain within existing relationships would be associated with an accelerated epigenetic aging profile among older adults in the Health and Retirement Study. Adults (N = 3,647) aged 50-100 years completed ratings of support and strain in relationships with their spouse, children, other family members, and friends. They also provided a blood sample that was used for DNA methylation profiling to calculate a priori-specified epigenetic aging measures: Horvath, Hannum, PhenoAge, GrimAge, and Dunedin Pace of Aging methylation (DunedinPoAm38). Generalized linear models that adjusted for chronological age, sex, and race/ethnicity and applied a false discovery rate correction revealed that the absence of marital and friend relationships related to an older GrimAge and faster DunedinPoAm38. Among those with existing relationships, lower support from a spouse, child, other family, and friends and higher strain with friends related to an older PhenoAge and GrimAge and faster DunedinPoAm38. In secondary analyses that further adjusted for socioeconomic and lifestyle factors, lower support from other family members and friends was associated with greater epigenetic aging. Findings suggest that the absence of close relationships and lower support within existing relationships-particularly with family members and friends-relate to accelerated epigenetic aging in older adulthood, offering one mechanism through which social relationships might influence risk for age-related declines and disease.

Cohabitation as a determinant of adaptive and innate immune cell profiles: Findings from the Health and Retirement Study.

Introduction: Non-genetic factors are important but poorly understood determinants of immune profiles. Age and Cytomegalovirus (CMV) infection remain two well documented non-genetic determinants of the immune profile. Recently, one study identified cohabitation in the same household as an important determinant of immune profiles. Methods: We used immunophenotyping data from the Health and Retirement Study (HRS) to evaluate the association between cohabitation and the adaptive (subsets of T-cells, B-cells) and innate immune profiles (subsets of monocytes, natural killer cells and neutrophils). We compared adaptive and innate immune cell profiles using immunophenotyping data from 1184 same-household pairs (cohabitating partners) to 1184 non-household pairs to evaluate the association between cohabitation and adaptive immune cell profiles. We used data from 1737 same-household pairs and 1737 non-household pairs to evaluate the association between cohabitation and innate cell profiles. Household and non-household pairs were matched on age (±2years), educational background and race/ethnicity to minimize confounding due to these factors. The adaptive immune cells and innate immune cell profiles were compressed to two coordinates using multidimensional scaling (MDS). The Euclidean distances between same-household pairs were compared to the distances between non-household pairs for the adaptive and innate cell profiles separately using two sample independent t-tests. We also performed additional adjustment for age and BMI differences, CMV serostatus and smoking concordance/discordance status among household members. Results: For adaptive immune cell profiles, the mean Euclidean distance between same-household pairs was 4% lower than the non-household pairs (p = 0.03). When stratified by concordance for CMV serostatus among household pairs, the Euclidean distance was significantly lower by 8% in the same-household pairs as compared to non-household pairs among those who were discordant for CMV serostatus (p = 0.01) and among same-household pairs who were CMV seronegative (p = 0.02) after covariate adjustment. The mean Euclidian distance between same-household pairs was also 8% lower than non-household pairs for the innate immune cell profiles (p-value <0.0001) and this difference remained consistent across all strata of CMV infection. Discussion: This study confirms that cohabitation is associated with similarity in immune cell profiles. The differential effects of cohabitation on the adaptive and innate immune profiles suggest that further studies into the common environmental factors that influence individual immune cell subsets need to be evaluated in greater detail.

Short sleep and insomnia are associated with accelerated epigenetic age.

OBJECTIVE: Short sleep and insomnia are each associated with greater risk for age-related disease, which suggests that insufficient sleep may accelerate biological aging. We examine whether short sleep and insomnia alone or together relate to epigenetic age among older adults. METHODS: A total of 3,795 men (46.3%) and women aged 56-100 years from the Health and Retirement Study were included. Insomnia was defined as reporting at least one insomnia symptom (difficulty falling asleep, waking up at night, or waking up too early in the morning) and feeling unrested when waking up most of the time. Those reporting <6 hours of bedtime were categorized as short sleepers. Three second- or third-generation epigenetic age acceleration clocks were derived from the 2016 HRS Venous Blood Study. The linear regression analysis was adjusted for age, sex, race/ethnicity, education, and obesity status. RESULTS: Insomnia and short sleep were associated with an 0.49 (95%CI:0.03-0.94; P:0.04) and 1.29 (95%CI:0.52-2.07; P:0.002) years acceleration of GrimAge, respectively, as well as a faster pace of aging (DunedinPACE; 0.018 (95%CI:0.004-0.033; P:0.02); 0.022(95%CI:-0.004-0.048; P:0.11)). Compared to healthy sleepers, individuals with the combination of short sleep and insomnia had an accelerated GrimAge (0.97 years; 95%CI:0.07-1.87; P:0.04) and a greater DunedinPACE (0.032; 95%CI:0.003-0.060; P:0.04). CONCLUSION: Our findings indicate short sleep, insomnia, and the combination of the two, are linked to epigenetic age acceleration, suggesting that these individuals have an older biological age that may contribute to risk for comorbidity and mortality.

Associations Between Change in Kidney Functioning, Age, Race/Ethnicity, and Health Indicators in the Health and Retirement Study.

BACKGROUND: The aging process is accompanied by decline in kidney functioning. It remains unknown to what extent age-related decline in kidney functioning can be attributed to health indicators, and whether rate of decline differs across sociodemographic groups. METHODS: Using data from the Health and Retirement Study from 2006/2008 through 2014/2016, we estimated kidney functioning trajectories, determined by cystatin C, among adults aged over 51 over 8 years. We evaluated the role of age, health conditions/behaviors, and genetics in the decline and also examined sociodemographic differentials. RESULTS: Kidney function declined with age and accelerated at older ages, even after adjusting for health conditions/behaviors and genetic differences (eg, 0.019 mg/L annual increase in cystatin C among 70-79 compared to 0.007 mg/L among 52-59 at baseline). Decline occurred faster among those with uncontrolled diabetes (0.008, p = .009), heart conditions (0.007, p < .000), and obesity (0.005, p = .033).Hispanic participants (0.007, p = .039) declined faster than non-Hispanic White persons due to diabetes, heart conditions, and obesity; non-Hispanic Black participants had worse baseline kidney functioning (0.099, p < .000), but only one fourth of this Black-White difference was explained by investigated risk factors. People with higher education experienced slower decline (-0.009, p = .004). CONCLUSIONS: Age was a significant predictor of decline in kidney functioning, and its association was not fully explained by health conditions/behaviors, or genetics. Better management of diabetes, heart conditions, and obesity is effective in slowing this decline. Baseline differences in kidney functioning (eg, between non-Hispanic White and Black persons; those with and without hypertension) suggest disparities occur early in the life course and require early interventions.

Pre-Analytical Variables Influencing Stability of Blood-Based Biomarkers of Neuropathology.

BACKGROUND: Sample collection and preanalytical protocols may significantly impact the results of large-scale epidemiological studies incorporating blood-based biomarkers of neuropathology. OBJECTIVE: To evaluate the stability and assay variability of several blood-based biomarkers of neuropathology for common preanalytical conditions. METHODS: We collected serum and plasma samples from 41 participants and evaluated the effect of processing delay of up to 72 h when stored at 4∘C, three freeze-thaw cycles, and a combination of 48-h processing delay when stored at 4∘C and three freeze-thaw cycles on biomarker stability. Using the Simoa assay (Quanterix Inc.), we measured amyloid-ß 40 (Aß40), amyloid-ß 42 (Aß42), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (p-tau-181). RESULTS: We found that Aß40 and Aß42 levels significantly decreased after a 24-h processing delay in both plasma and serum samples, and a single freeze-thaw cycle (p < 0.0001). Nevertheless, serum Aß42/40 ratio remained stable with a processing delay up to 48 h while plasma Aß42/40 ratio showed only small but significant increase with a delay up to 72 h. Both plasma and serum GFAP and NfL levels were only modestly affected by processing delay and freeze-thaw cycles. Plasma p-tau-181 levels notably increased with a 24-, 48-, and 72-h processing delay, but remained stable in serum. Intra-individual variation over two weeks was minimal for all biomarkers and their levels were substantially lower in serum when compared with plasma. CONCLUSION: These results suggest that standardizing preanalytical variables will allow robust measurements of biomarkers of neuropathology in population studies.

Systems Age: A single blood methylation test to quantify aging heterogeneity across 11 physiological systems.

Individuals, organs, tissues, and cells age in diverse ways throughout the lifespan. Epigenetic clocks attempt to quantify differential aging between individuals, but they typically summarize aging as a single measure, ignoring within-person heterogeneity. Our aim was to develop novel systems-based methylation clocks that, when assessed in blood, capture aging in distinct physiological systems. We combined supervised and unsupervised machine learning methods to link DNA methylation, system-specific clinical chemistry and functional measures, and mortality risk. This yielded a panel of 11 system-specific scores- Heart, Lung, Kidney, Liver, Brain, Immune, Inflammatory, Blood, Musculoskeletal, Hormone, and Metabolic. Each system score predicted a wide variety of outcomes, aging phenotypes, and conditions specific to the respective system, and often did so more strongly than existing epigenetic clocks that report single global measures. We also combined the system scores into a composite Systems Age clock that is predictive of aging across physiological systems in an unbiased manner. Finally, we showed that the system scores clustered individuals into unique aging subtypes that had different patterns of age-related disease and decline. Overall, our biological systems based epigenetic framework captures aging in multiple physiological systems using a single blood draw and assay and may inform the development of more personalized clinical approaches for improving age-related quality of life.