Demographic Research

Background: Associations between individual socioeconomic indicators and biological aging leave open whether the pattern extends across social origin, attained education, and economic resources. I examined these aspects of socioeconomic position and educational mobility in relation to Klemera-Doubal method (KDM) age acceleration across 12 countries in the Survey of Health, Ageing and Retirement in Europe (SHARE), and whether cross-country variation in these associations followed a welfare-state or economic-development pattern. Methods: Using SHARE Wave 6 (2015), I constructed three sex-specific KDM measures from overlapping biomarker panels in 10,043-14,015 adults aged 50-75 years and followed outcomes through Wave 9. Predictive validity was assessed for ADL/IADL limitations, cognition, and mortality. Survey-weighted models estimated pooled SES associations and tested country heterogeneity; exploratory analyses summarized multidimensional country profiles and examined six national indicators. Results: All three KDM measures were prospectively associated with incident functional limitation, lower cognition, and mortality; ADL/IADL odds ratios ranged from 1.29-1.61 and mortality hazard ratios from 1.44-1.92. Across all 21 pooled coefficients, greater socioeconomic advantage was associated with lower KDM age acceleration; each of the six specification-level tests had a false-discovery-rate-adjusted P<0.05 for every KDM outcome. KDM age acceleration was 0.076-0.107 SD lower per 1-SD higher respondent education and 0.060-0.076 SD lower per 10-percentile higher wealth or income rank. In joint origin-destination models, higher respondent-destination rank was consistently associated with lower KDM acceleration, whereas conditional parental-origin coefficients were smaller and compatible with zero. 11 of 18 country-heterogeneity tests had adjusted P<0.05; KDM9 respondent-education slopes ranged from -0.213 to 0.054 SD, with negative point estimates in 11 of 12 countries. Ordered country profiles showed no obvious welfare-state or economic-development hierarchy, and none of six contemporaneous national indicators robustly accounted for the variation after multiplicity adjustment. Conclusions: Across indicators of social origin, attained education, and current and accumulated economic resources, greater socioeconomic advantage was consistently associated with lower KDM age acceleration. The magnitudes of these associations also varied materially across affluent national settings and did not reduce to a welfare-state or economic-development ordering. Thus, pooled estimates capture a common pattern of socioeconomic stratification while potentially obscuring meaningful national variation in its strength; the absence of a simple contextual ordering adds a biological-aging dimension to the broader welfare-state puzzle.

Early life adversity is a recognised risk factor for poor health in later life, but its relationship with allostatic load (AL; a measure of cumulative physiological stress) remains underexplored across populations around the world. This study builds evidence to test a life course approach to AL using harmonised data from six longitudinal ageing cohorts: Health and Retirement Study (US, N=2,427), English Longitudinal Study of Ageing (England, N=2,038), The Irish Longitudinal Study on Ageing (Ireland, N=8,184), Survey of Health Ageing and Retirement in Europe (Europe, N=4,079), China Health and Retirement Longitudinal Study (China, N=5,220), and Indonesia Family Life Survey (Indonesia, N=1,243). Childhood information at aged ten to sixteen was collected retrospectively from adults aged 65 on average. An AL score is constructed using biomarker data and a latent construct of early life adversity constructed to address recall bias. Results show that early life poverty is significantly associated with raised AL in Ireland, China, and Indonesia, supporting the impact of early life experiences on older adulthood. However, studies from other countries do not confirm statistical significance. These findings document that experiencing poverty during development phase in some settings is associated with higher AL in later life, however further analyses are required to explore possible variations across different populations and their social and economic context. These results add further evidence that social determinants of health, including child poverty, in some settings, contribute to cumulative physiological stress across the life course, and that policies and actions to reduce child poverty can have beneficial effects not only as children, but also as older adults.

The COVID-19 pandemic and pandemic response may have long-term consequences. The cumulative impact may be better appraised when post-pandemic years are also considered. For 38 populations with reliable death registration data, we estimated excess deaths for 2020-2025 with 4 models and granular age stratification. The Fa model compared deaths against the mean of 2017-2019. Three other trend models considered changes in mortality rates after 2003 (or after a country reached $20,000 per capita income) factoring trend-of-trends (TTa), including shrinkage (STTa), and factoring also the 2024-2025 data for trend-of-trends calculation (STTa). Slopes (weighted mean -0.58%/year in 2019) and slopes-of-slopes (weighted mean +0.106%/year-squared) for age-stratified mortality rates were highly heterogeneous across populations. On model average, 6 populations (Luxembourg, Ireland, Sweden, New Zealand, Denmark, Korea) had cumulative death deficits during 2020-2025, while another 6 (Chile, Bulgaria, Japan, Greece, USA, Italy) had >4% excess deaths. Differences across populations were more prominent during 2020-2023, while 33/38 countries had estimated death deficits in 2024-2025. Total 2020-2025 excess deaths were 1.16-2.63 million (2020-2023: 2.19-3.03 million; 2024-2025: -1.03 to -0.40 million deficit). Lack of age stratification and use of unchanged linear trends for the baseline grossly biased excess death estimates upwards. Socioeconomically more vulnerable populations had higher pandemic deaths, but a more pronounced post-pandemic death deficit. Excess death estimates require careful consideration of changing population age structure and long-term mortality trajectories. Post-pandemic death deficits, especially in more vulnerable populations, may reflect deaths of people with modest life expectancy during the pandemic with respective pay off in 2024-2025

Background: Retirement is a major life transition that may influence cognitive aging. Retirement pathways are becoming increasingly diversified, yet evidence on how heterogeneous retirement trajectories relate to dementia risk remains limited. This study used sequence and cluster analysis to characterize thousands of transition-to-retirement trajectories, including retirement timing and work intensity, to estimate associations with dementia risk. Methods: We used data from 13,879 participants in the U.S. Health and Retirement Study. Our exposure was transition-to-retirement trajectories between ages 51 and 75 identified using sequence and cluster analysis. Our outcome was a validated algorithmically derived dementia probability measure. We estimated associations between trajectory clusters and dementia risk beginning at age 76 using generalized estimating equations, adjusting for sociodemographic characteristics. Inverse probability weights were used to account for attrition. Results: We identified ten distinct transition-to-retirement trajectories characterized by differences in timing of retirement, part-time work, disability, and labor force attachment. Compared with individuals retiring after full-time work in their early-to-mid 60s, dementia risk was similar among those retiring earlier or later from full-time work. In contrast, individuals with sustained part-time employment between ages 51 and 75 had lower odds of dementia (OR: 0.62, 95% CI: 0.48, 0.80), while trajectories characterized by prolonged disability were associated with higher odds of dementia (OR: 1.53, 95% CI: 1.22, 1.91). Conclusions: Retirement timing alone showed limited association with later-life dementia risk, whereas sustained part-time employment and disability-related trajectories were more strongly associated with dementia risk. These findings suggest that employment intensity and health-related exit from the labor force may be more relevant for dementia risk than retirement timing, and that gradual and flexible work-to-retirement transitions may benefit brain health. Background: Retirement is a major life transition that may influence cognitive aging. Retirement pathways are becoming increasingly diversified, yet evidence on how heterogeneous retirement trajectories relate to dementia risk remains limited. This study used sequence and cluster analysis to characterize thousands of transition-to-retirement trajectories, including retirement timing and work intensity, to estimate associations with dementia risk. Methods: We used data from 13,879 participants in the U.S. Health and Retirement Study. Our exposure was transition-to-retirement trajectories between ages 51 and 75 identified using sequence and cluster analysis. Our outcome was a validated algorithmically derived dementia probability measure. We estimated associations between trajectory clusters and dementia risk beginning at age 76 using generalized estimating equations, adjusting for sociodemographic characteristics. Inverse probability weights were used to account for attrition. Results: We identified ten distinct transition-to-retirement trajectories characterized by differences in timing of retirement, part-time work, disability, and labor force attachment. Compared with individuals retiring after full-time work in their early-to-mid 60s, dementia risk was similar among those retiring earlier or later from full-time work. In contrast, individuals with sustained part-time employment between ages 51 and 75 had lower odds of dementia (OR: 0.62, 95% CI: 0.48, 0.80), while trajectories characterized by prolonged disability were associated with higher odds of dementia (OR: 1.53, 95% CI: 1.22, 1.91). Conclusions: Retirement timing alone showed limited association with later-life dementia risk, whereas sustained part-time employment and disability-related trajectories were more strongly associated with dementia risk. These findings suggest that employment intensity and health-related exit from the labor force may be more relevant for dementia risk than retirement timing, and that gradual and flexible work-to-retirement transitions may benefit brain health.

This cross-sectional study examined the associations of education and body mass index (BMI) with handgrip strength among older adults from the United States, China, and Europe, and quantified education-related inequalities across these populations. We used data from the National Health and Nutrition Examination Survey (NHANES, 2011-2014, n=5,267), the China Health and Retirement Longitudinal Study (CHARLS, 2015, n=16,631), and the Survey of Health, Ageing and Retirement in Europe (SHARE, Wave 6, 2015, n=21,997). Participants were community-dwelling adults aged 50-80 years. Handgrip strength was measured using handheld dynamometers, with maximum values used for analysis. Education was harmonized into three categories (Low, Middle, High). Multivariable linear regression, the Slope Index of Inequality (SII), and association decomposition were employed. European older adults exhibited the highest crude grip strength (mean 34.3 kg), followed by Chinese (31.0 kg) and American (28.8 kg) counterparts. Higher education was significantly associated with greater grip strength in all cohorts. Education-related inequality was greatest in China (SII=4.22, 95% CI: 3.91-4.52) and smallest in the United States (SII=1.67, 95% CI: 1.26-2.08). The educational effect was strongest among European males (3.48 kg) and weakest among Chinese females (0.79 kg). BMI exhibited a suppression pattern rather than mediation, with negative proportional contributions in NHANES (-7.4%) and SHARE (-4.8%). Sensitivity analyses confirmed the robustness of these findings. Considerable cross-national heterogeneity exists in education-related grip strength disparities, with the educational advantage most pronounced in Europe and least effective in China, particularly among women.

Features of urbanicity have been linked to poor psychiatric health in adulthood, but little is known about their relationship with biological age and cognition earlier in life. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we tested associations between the built environment and epigenetic ages (EpiAgeAltum, EpiAgeHorvath, EpiAgePACE) (n=2,452), brain age (n=751), and cognition (n=12,199). Analyses were replicated in Generation R and triangulated in the Millennium Cohort Study. The built environment was not associated with epigenetic ages ({beta}Altum range = 0.013-0.015, p range = .466-.689; {beta}Horvath range = -0.011-0.023, p range = .182-.728; {beta}PACE range = -0.045-0.013, p range = .131-.524) or brain age ({beta} range = 0.022-0.028, p range = .337-.429). A negative association with cognition was observed in Generation R. We provide no consistent evidence that childhood built environment exposure relates to biological age and cognition in adolescence, suggesting these relationships may emerge in later life.

Background: Hearing loss (HL) may be a risk factor for poor psychosocial outcomes among older adults, but evidence remains mixed. We assessed associations of self-reported and objective HL with and without hearing aid use with social contact, loneliness, and depression pooled across 6 years of follow-up. Methods: We studied 2049 Black and White adults from the Health, Aging, and Body Composition study aged 70-79 at recruitment. Self-reported HL and audiometric HL with and without hearing aid use were assessed at analytic baseline (Year 5, 2001-2002). Outcomes were frequency of contact with family and friends (<weekly vs. at least weekly), depressive symptoms (CESD-10), and loneliness (CESD-10 item "I felt lonely") measured across 6 annual visits. Adjusted for demographic and clinical variables, we used generalized linear regression with generalized estimating equations to assess associations with outcomes pooled across six follow-up waves. Results: Self-reported HL (16%) was associated with more depressive symptoms ({beta}=0.13 SD; 95%CI:0.03,0.24), but no other outcome. Objective HL without hearing aid use (11%) was associated with infrequent contact with friends (OR=1.38; 95%CI:1.07,1.78) and more depressive symptoms ({beta}=0.19 SD; 95%CI:0.07,0.31); objective HL with hearing aid use (9%) was not associated with these outcomes. Objective HL, regardless of hearing aid use, was borderline associated with more frequent feelings of loneliness. Discussion: Objective HL without hearing aid use may be an important risk factor for isolation from friendship networks and depressive symptoms among older adults. Self-reported HL and objective HL with hearing aid use may also be linked to some adverse psychosocial outcomes.

Background Attentional control declines with normal aging, yet the role of modifiable lifestyle factors in accelerating this decline remains incompletely characterised in large, diverse populations. We examined associations between four modifiable risk factors (smoking intensity, alcohol binge drinking, social satisfaction and blood pressure) and sustained attention performance in 13,866 adults drawn from the All of Us Research Program. Methods Cognitive performance was assessed using the Gradual-Onset Continuous Performance Task (GradCPT). A composite cognitive efficiency score was derived via principal component analysis of four GradCPT metrics: d' (perceptual sensitivity), response criterion, median reaction time and reaction time variability. Associations between cognitive efficiency and each risk factor were examined using multiple linear regression adjusted for age, sex and race/ethnicity. Effect sizes were expressed as age-equivalent years of cognitive aging (age-equivalent years = regression coefficient for the risk factor divided by the regression coefficient for age) to aid clinical interpretation. Results GradCPT performance declined progressively with age (p < 0.001). Social satisfaction emerged as the strongest lifestyle predictor: low social satisfaction was associated with approximately 5.8 additional age-equivalent years of cognitive aging relative to high social satisfaction. Smoking showed a dose-response pattern, with heavy smokers (> 20 cigarettes/day) exhibiting an approximately 5-year age-equivalent deficit versus never-smokers. Stage 2 hypertension showed a modest, non-significant negative association. Binge drinking showed limited significant associations, likely complicated by survivor and abstainer biases. Bootstrapped analyses of combined exposures showed that combinations of risk factors, particularly those involving low social satisfaction, produced larger cognitive deficits than expected under an additive model. Conclusions These findings support an interactive rather than a purely additive model of lifestyle-related cognitive vulnerability and highlight the GradCPT as a subclinical measure of attention-based cognitive risk in non-clinical populations. Keywords Cognitive aging, Sustained attention, GradCPT, Modifiable risk factors, Social isolation, Smoking, Hypertension, All of Us Research Program

Objective This study evaluated how well subjective life expectancy (SLE) predicts mortality and actual life expectancy (ALE), along with factors associated with inaccurate expectations. Methods Using panel data on approximately 2,000 individuals with up to 28 years of follow-up from a nationally representative sample of older Japanese adults, we examined relationships among SLE, actual mortality, and ALE by survival analysis. We also evaluated health and socioeconomic disparities using concentration indices and investigated factors influencing SLE and ALE discrepancies and focal-point (i.e. rounded or anchored estimates) and do-not-know responses. SLE was measured as a self-reported point estimate, whereas ALE mainly came from official records and family reports. Results SLE was significantly associated with both actual mortality and ALE, even after accounting for demographic and socioeconomic variables. Nonetheless, significant inaccuracies remain: approximately 59% of individuals surpassed their expected lifespan. SLE was positively associated with ALE; however, the association was inelastic. Women and those with higher education levels were more likely to outlive their SLE, whereas those in poorer health were less likely to do so. Higher education correlated with fewer focal point responses to the SLE question. Discussion SLE effectively predicts ALE; however, gaps are non-negligible and differ across gender and socioeconomic groups. Offering more precise data, such as sex- and age-specific remaining life expectancy, can enhance SLE formation and lead to more informed economic choices.

Importance: Long-term exposure to higher average air pollutant concentrations is associated with poorer cognitive health, but annual averages can obscure substantial differences in day-to-day exposure. Whether recurrent high pollution days are associated with long-term cognitive aging trajectories among people with similar overall air pollution exposure is unclear. Objective: To determine whether the annual number of days exceeding World Health Organization daily guideline values for nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) is associated with subsequent cognitive decline after accounting for annual mean air pollutant exposure. Design: Prospective cohort study using data from waves 1-10 (2002-03 to 2021-23) of the English Longitudinal Study of Ageing. Setting: Population-based cohort of community-dwelling adults in England. Participants: 12,235 adults aged 50+ years at analytic baseline. Exposures: Number of days exceeding World Health Organization daily guideline values ('exceedance days') for NO2, PM2.5, and PM10, derived from residence-linked environmental estimates during the calendar year preceding the analytic baseline. Main Outcomes and Measures: Baseline cognitive performance and model-estimated 14-year cognitive decline (corresponding to the 75th percentile of follow-up duration) in episodic memory and verbal fluency. Results: Exceedance days were not associated with baseline memory or verbal fluency after adjustment for annual mean air pollutant exposure. More NO2 exceedance days were associated with faster cognitive decline: comparing the 75th percentile with the median of NO2 exceedance days, the difference in 14-year decline was -0.09 SD (95% CI, -0.17 to -0.01; p = 0.02) for memory and -0.10 SD (95% CI, -0.19 to 0.00; p = 0.04) for fluency. PM2.5 and PM10 exceedance days were not associated with cognitive decline. Conclusions and Relevance: In this cohort study of older adults, a higher number of NO2 exceedance days was associated with faster subsequent cognitive decline after adjustment for annual mean air pollutant exposure. This suggests that daily exposure to high NO2 concentrations may be related to accelerated cognitive aging even when offset by lower exposure on other days, potentially providing a new rationale for identifying and prioritizing areas with recurrent high NO2 exposure and the local emission sources contributing to it.

Chronic social deficits (persistent feelings of being lonely or isolated) have been linked to premature mortality, yet the underlying physical and mental pathways remain unclear. This study used data from 4,090 older adults in the English Longitudinal Study of Ageing, a longitudinal panel study. Using outcome-wide analyses, we assessed how the chronicity of social deficits was associated with 17 health outcomes across physical, mental, cognitive and behavioural health domains. Regression models showed that chronic loneliness was longitudinally associated with increased risks of worse general health, functional capacity, and mental wellbeing, and more unhealthy behaviours. Chronic isolation and onset of isolation were associated with lower quality of life, whereas isolation remission was positively related to enhanced mental wellbeing and cognition compared to no isolation. Findings suggest an association between chronicity of loneliness and adverse health outcomes, highlighting chronic social deficits as an important correlate of healthy ageing.

Background: Lebanon is undergoing substantial demographic and social change, with older adults comprising approximately 10% of the population. The Late Life Learning, Cognition, and Aging (3LC) study was established around the University for Seniors (UfS), a longstanding late-life learning program at the American University of Beirut. The cohort was designed to leverage variation in late-life learning exposure by including both UfS participants and community-dwelling adults without prior participation in the program. This provides a unique opportunity to investigate how late-life learning, lifecourse social and biological factors, and health behaviors relate to cognitive aging, dementia risk, mental health, and resilience in Lebanon. Methods: Participants aged 50 years and older are recruited from the UfS program and the surrounding community in Lebanon. Baseline assessments include an interviewer-administered questionnaire, standardized anthropometric and sensory assessments, and blood collection for biomarker measurement and biobanking. The questionnaire captures health, psychosocial, cognitive, social engagement, and lifecourse factors, including exposure to war, conflict, and socioeconomic adversity. Longitudinal follow-up includes planned phone-based and in-person assessments at approximately two-year intervals. Results: The cohort comprised 1,871 participants, including 536 UfS participants (350 previously enrolled and 186 newly enrolled) and 1,335 community participants, of whom 1,041 were age-, sex-, and education-matched to UfS participants and 294 were additionally recruited without matching. The mean age was 65.6 years (SD=9.0), and 70.1% of participants were women. Blood samples were obtained from 1,541 participants (82.3%). Conclusion: The 3LC study provides a unique platform to examine how late-life learning and lifecourse factors shape cognitive aging, well-being, and dementia risk in Lebanon. By integrating social, psychosocial, health, and biological measures, the cohort offers opportunities to identify modifiable determinants of cognitive aging and inform dementia prevention in Lebanon and other under-resourced settings.

Financial well-being (FWB) encompasses objective and subjective financial status and may influence health. We developed and validated a parsimonious FWB index using data from 23,006 Health and Retirement Study (HRS) participants aged 50 years and older from 2006 to 2022. The FWB-5 Index was derived using correlated two-factor confirmatory factor analysis accounting for household clustering. Indicators included household wealth, household income-to-poverty ratio, monthly financial strain, satisfaction with one's financial situation, and perceived financial mastery. We assessed convergent and discriminant validity using the Consumer Financial Protection Bureau Financial Well-Being (CFPB-FWB) Scale and Satisfaction with Life Scale, respectively. Associations with pre-baseline socioeconomic factors and subsequent depressive symptoms and health conditions were examined to assess construct and predictive validity. Model fit indices supported the two-factor structure (robust comparative fit index = 0.99; robust root mean square error of approximation = 0.05). Correlations were stronger with the CFPB-FWB Scale (Spearman P = 0.80) than with life satisfaction (Spearman P = 0.43). Associations with socioeconomic factors and subsequent health outcomes were in the hypothesized directions. These findings support the FWB-5 Index as a parsimonious measure for examining financial well-being and its associations with health across HRS waves, including those predating the CFPB-FWB Scale.

Background: Suicide rates are highest among older adults. Yet, little is known regarding differences in suicide risk of older adults in Austria. This nationwide, retrospective cohort study aimed to characterize suicides among older adults in Austria during 2014-2023 and examine differences those who were young-old (65-74), middle-old (75-84), and oldest-old (85 +). Methods: We applied a cohort design to individual-level linkage data on all residents in Austria aged 65 years and older during 2014-2022 (N = 2,442,939). We compared characteristics of individuals who died by suicide and other causes of death, as well as by age group (i.e., young-old, middle-old, oldest-old) using trend tests and odds ratios. We calculated crude incidence rates of suicide per age group and sex. Results: During 2014-2023, 4,724 older adults died by suicide in Austria. The overall suicide rate was 23.4 per 100,000 person-years, while males had higher rates than females. Suicide rates increased with age and peaked among the oldest-old (33.2/100,000). Hanging, firearms, and jumping were the predominant methods, and the prevalence of hanging increased relative with increasing age. With increasing age, also widowhood and cardiovascular and genitourinary disorders were more prevalent among those who died by suicide. Conclusions: In Austria, oldest-old adults have the highest suicide rates, especially for males. whereas rates were considerably lower and did not change throughout old age for females. Distinct differences in suicide rates with respect to marital status, health conditions, and suicide methods. This emphasizes the need for preventive strategies to target older adults at different stages of life.

Introduction. Perceived neighborhood problems (PNP), such as safety concerns and limited resources, have been linked to elevated hypertension risk through chronic stress pathways. The Identity Vitality Pathology (IVP) framework captures the extent to which individuals experience threats to identity, belonging, and psychosocial vitality in the face of structural disadvantage, and may modify these pathways. Methods. We conducted logistic regression analyses to estimate the association between PNP and hypertension. Models were stratified by race and gender groups (Black women, Black men, White women, White men). Both main effects models and adjusted models included an interaction term between PNP and Identity Vitality Pathology score (IVPS) to assess effect modification. Adjusted models controlled for age, education, perceived support, financial strain, physical activity, diabetes, smoking status, and self-rated health. Interaction terms were used to evaluate whether the association between PNP and hypertension varied by levels of IVPS within each race/gender group. Results. Higher PNP was associated with increased odds of hypertension among White women and men, but not consistently among Black women and men. Identity state moderated this association only among Black women, such that each 1-SD increase in IVPS score was associated with 59% lower odds of hypertension at the highest level of PNP (aOR-0.41; 95% CI: 0.19, 0.88), with no meaningful moderation observed in other groups. Conclusion. Identity state may moderate the association between subjective neighborhood disadvantage and hypertension, particularly among Black women, representing a potentially novel, modifiable protective factor among multiply marginalized persons living in communities with increased risk for hypertension.

Health inequalities are often examined through single axes such as class or ethnicity, obscuring how these dimensions interlock. This study applies a longitudinal intersectional approach to examine physical and mental health trajectories across five generations in the UK. We analysed 14 waves of the UK Household Longitudinal Study (2009-2024) using longitudinal Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA). We modelled SF-12 physical and mental health trajectories for 398 intersectional strata defined by gender, ethnicity, occupational class, and generation. Physical health inequalities widened with age, consistent with cumulative disadvantage, while mental health inequalities were more evident among later-born cohorts. The 'Boomer' generation exhibited a relatively flat mental health trajectory across its observed age range. In contrast, 'Generation Z' had lower predicted mental health, particularly among White British women with no work history - a group with poorer predicted trajectories than their South Asian peers. Our study shows how health inequalities are structurally differentiated by cohort and intersectional position. Policy responses should support proportionate universalism, combining broad population-level support with intensified action for groups showing poorer health.

Introduction Guatemala is the most populous country in Central America and a setting with unique opportunities for aging research. Approximately 40% of Guatemala's population is Indigenous Maya, who together speak 22 Mayan languages. Currently, there is no population-based aging study in Guatemala and few aging studies in Latin America among Indigenous populations. The Longitudinal Study of Aging in Guatemala (ELEGUA) aims to address these gaps by developing a nationally representative, population-based, longitudinal aging study modeled on the Health and Retirement Study and the Harmonized Cognitive Assessment Protocol, adapted to the cultural and linguistic context of Guatemala. The objective of this protocol is to describe the rationale and design of the ELEGUA pilot survey. Methods and analysis The ELEGUA pilot was a cross-sectional household survey of adults aged 40 years or older in Tecpan, Guatemala. Tecpan was chosen because its diverse population facilitated testing of study procedures in both Spanish and Kaqchikel, a common Mayan language. The survey included up to 600 households sampled using a multistage stratified cluster design. Within each household, one individual aged 40 years or older was selected, with oversampling of adults aged 55 years or older. This respondent completed a comprehensive questionnaire, including detailed cognitive tests, and provided physical measurements and a venous blood sample. Household respondents provided information on household economics and family structure, and an informant reported on the individual respondent's cognitive function. Data were collected using a computer-assisted personal interviewing system. Planned analyses include survey-weighted descriptive statistics and psychometric evaluation of the cognitive assessments. Ethics and dissemination Ethics approval was obtained from the ethics committees of the Institute of Nutrition of Central America and Panama, Maya Health Alliance, and the University of Michigan. Results will be disseminated through publications in peer-reviewed journals and presentations to local, national, and international audiences.

Background: Associations of sleep duration and insomnia symptoms with cognitive decline are inconsistent, and whether they represent modifiable risk factors or early manifestations of neurodegeneration may depend on life stage. We examined how sleep-cognition associations vary with age (44 to >90 years). Methods: We studied 16,884 participants from three cohorts with harmonised measures. In the English Longitudinal Study of Ageing (ELSA: n=9,473, median age 64, range 50 to >=90), linear mixed-effects models examined age-specific differences in cognitive change (recall and fluency) associated with sleep duration, difficulty falling asleep, nocturnal awakenings, incorporating sleep-by-age-by-time interactions, with initial adjustment for sociodemographic factors and further adjustment for health and lifestyle factors. Sleep characteristics showing consistent age-dependent associations in ELSA were further evaluated in Whitehall II (n=5,580, median age 55, range 44 to 68) and the Rush Memory and Aging Project (MAP: n=1,831, median age 80, range 53 to 102). Findings: In ELSA, difficulty falling asleep >=1 time/week (vs <1 time/week) was associated with less favourable 5-year change in recall at age 50 (difference -0.12 SD, 95% CI -0.20 to -0.04), with the association attenuating and reversing towards more favourable change at older ages (p-interaction=0.009 [linear], 0.016 [quadratic]). These persisted after further adjustment for health and lifestyle factors. Short sleep (<=6 h) showed similar patterns that attenuated after further adjustment. Similar age gradients were observed for difficulty falling asleep in Whitehall II and MAP. There was no evidence of age modification on long sleep and nocturnal awakenings. Interpretation: The cognitive implications of sleep disturbances vary by life stage. In midlife, difficulty falling asleep was associated with faster cognitive decline, supporting its role as a modifiable risk factor. In advanced age, the reversal is consistent with diminished arousal capacity accompanying prodromal dementia. Funding: US National Institute on Aging

Recent lifespan frameworks of aging theorize that pubertal development and cellular aging are governed by overlapping pathways, but the time lag between adolescence and older adulthood complicates the study of shared molecular mechanisms. Here we compare a DNA-methylation-based epigenetic index of pubertal development to epigenetic clocks, which were designed to measure biological aging, as a putative biomarker of adult aging and health in two adult cohorts: 3,642 older Americans in the Health and Retirement Study (HRS; age range, 56 to 100 years; 2,106 females) and 18,676 adults from Generation Scotland (GS; age range, 18 to 98 years; 10,974 females). Epigenetic puberty was correlated with chronological age in both cohorts, moderately in the older HRS sample (r = 0.51 in females, r = 0.51 in males) and strongly across the wider adult age range of GS (r = 0.82 in females, r = 0.86 in males). In both cohorts, age-residualized epigenetic puberty was associated with accelerated biological aging as measured by epigenetic clocks and other aging biomarkers (standardized coefficients: HRS, 0.13 to 0.47, all P < 0.005; GS, 0.05 to 0.40, all P < 0.001). Epigenetic puberty was linked with multiple health outcomes: mortality in HRS in both sexes (ORs, 1.39 and 1.46, both P [&le;] 0.001) and in GS among females (HR, 1.12, P = 0.003); 10-year onset of diabetes, any cancer and lung disease in GS (HRs, 1.12 to 1.19, all P < 0.005); and with multimorbidity, functional limitations and BMI in females in HRS (standardized coefficients, 0.10 to 0.16, all P < 0.001). It also accounted for a unique, albeit smaller, proportion of variance in aging-related outcomes beyond that explained by epigenetic clocks. These findings indicate that the epigenetic puberty index reflects pro-aging underlying biology, showing overlapping molecular pathways between pubertal development and cellular aging, and support a lifespan-based approach to studying biological aging.

Despite recent evidence of the ability of systemic and organ-specific proteomic aging clocks to predict a large range of age-related diseases, their utility in cancer research remains largely underexplored. In this study, we evaluated the predictive ability of systemic and organ-specific proteomic aging clocks for (i) all-cause mortality, (ii) cancer-related mortality, and (iii) cancer incidence in a sample of Finnish twins (N = 401, mean age at baseline 62.3 years) with Olink proteomic data. Participants were followed for a mean of 10.6 years (SD +- 1.6), with estimates from four systemic and 18 organ-specific proteomic aging clocks calculated at baseline. Cox proportional hazards regression models adjusted for sex and age at baseline identified 15 proteomic aging clocks as significant predictors of all-cause mortality (Ncases = 28) after multiple testing correction (FDR < 0.05), with 11 remaining significant after lifestyle adjustment (Ncases = 27). For several clocks, effect sizes were large, with hazard ratios (HR) approximately doubling per one standard deviation (SD) increase in clock estimates. In predicting cancer-related deaths among participants without a prior cancer diagnosis at baseline (Ncases = 9), only the Immune clock showed a significant positive association after multiple testing correction in basic (HR = 2.94, 95% CI: 1.88-4.59) and lifestyle-adjusted models (HR = 3.31, 95% CI: 1.78-6.17). No associations with cancer incidence (Ncases = 34 basic, Ncases = 31 adjusted) survived multiple testing correction, although several nominal associations were observed. In conclusion, our findings suggest that proteomic aging clocks are strong predictors of all-cause and cancer-specific mortality, independent of lifestyle factors. Proteomic aging clocks may further serve as valuable tools for stratifying cancers by mortality risk.