Background: Despite a clear link between aging and cancer, there has been inconclusive evidence on how biological age (BA) may be associated with cancer incidence. Methods: We studied 308,156 UK Biobank participants with no history of cancer at enrolment. Using 18 age-associated clinical biomarkers, we computed three BA measures (Klemera-Doubal method [KDM], PhenoAge, homeostatic dysregulation [HD]) and assessed their associations with incidence of any cancer and five common cancers (breast, prostate, lung, colorectal, and melanoma) using Cox proportional-hazards models. Results: A total of 35,426 incident cancers were documented during a median follow-up of 10.9 years. Adjusting for common cancer risk factors, 1-standard deviation (SD) increment in the age-adjusted KDM (hazard ratio = 1.04, 95% confidence interval = 1.03–1.05), age-adjusted PhenoAge (1.09, 1.07–1.10), and HD (1.02, 1.01–1.03) was significantly associated with a higher risk of any cancer. All BA measures were also associated with increased risks of lung and colorectal cancers, but only PhenoAge was associated with breast cancer risk. Furthermore, we observed an inverse association between BA measures and prostate cancer, although it was attenuated after removing glycated hemoglobin and serum glucose from the BA algorithms. Conclusions: Advanced BA quantified by clinical biomarkers is associated with increased risks of any cancer, lung cancer, and colorectal cancer.

Background: We examined the association of housing affordability with physical and mental health in Hong Kong, where there is a lack of related research despite having the worst housing affordability problem in the world, considering potential mediating effect of deprivation. Methods: A stratified random sample of 1978 Hong Kong adults were surveyed. Housing affordability was defined using the residual-income (after housing costs) approach. Health-related quality of life was assessed by the Short-Form Health Survey version 2 (SF-12v2), from which the physical component summary (PCS) and mental component summary (MCS) measures were derived. Multivariable linear regressions were performed to assess associations of housing affordability with PCS and MCS scores, adjusting for sociodemographic, socioeconomic and lifestyle factors. Mediation analyses were also conducted to assess the mediating role of deprivation on the effect of housing affordability on PCS or MCS. Results: Dose–response relationships were observed between housing affordability and mean PCS score (β (95% CI) compared with the highest affordable fourth quartile: −2.53 (−4.05 to −1.01), −2.23 (−3.54 to −0.92), −0.64 (−1.80 to 0.51) for the first, second and third quartiles, respectively) and mean MCS score (β (95% CI): −3.87 (−5.30 to –2.45), −2.35 (−3.59 to −1.11), −1.28 (−2.40 to –0.17) for the first, second and third quartiles, respectively). Deprivation mediated 34.3% of the impact of housing unaffordability on PCS and 15.8% of that on MCS. Conclusions: Housing affordability affects physical and mental health, partially through deprivation, suggesting that housing policies targeting deprived individuals may help reduce health inequality in addition to targeting the housing affordability problem.

There has been a rising trend of labor migration globally. Given their alien status within the legal framework of the host countries, migrant domestic workers (MDWs) are especially vulnerable to poor employment conditions that may affect their health status, yet there is still a lack of quantitative evidence in this population hitherto. Using randomly sampled data from a cross-sectional survey of 2,017 live-in female MDWs in Hong Kong, a setting with a high concentration of MDWs, this study examined the association of employment conditions with physical and mental health among the MDWs. We observed poorer physical and mental health status among the MDWs when compared with the general population in Hong Kong. Our findings suggest that employment conditions, including household size, working on the rest day, and housing type, and age were associated with physical health, while employment conditions, including not ever receiving wages on time, frequency of financial remittances, paying the employment agency, having a private room, fulfillment of work-related needs, physical abuse, and discrimination, and sociodemographic characteristics, including age and duration of migration, were associated with mental health. Social support in general did not confound these associations, but religious activities and daily contact with friends were also associated with mental health. Our findings have important implications in designing interventions and policies to improve the physical and mental well-being of this vulnerable migrant population.

The comparative effectiveness of glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas on the risk of dementia in older individuals with type 2 diabetes mellitus (T2DM) is unknown. We conducted a sequential trial emulation from 1st January 2010 to 30th June 2020 using data from Swedish national registers. Swedish residents who were aged 65 or older, had type 2 diabetes (T2DM), and initiated GLP-1 agonists, DPP-4 inhibitors, or sulfonylureas were followed for up to 10 years to assess the risk of dementia. Participants who had dementia, used the three drug classes, or had contraindications were excluded from enrollment. The characteristics between arms were balanced through the application of propensity scores estimated from predefined covariates. Intention-to-treat effects were analysed with all enrolled participants, while the per-protocol effects were analysed with participants who adhered to the assigned treatment. The pooled trial included 88,381 participants who received prescriptions for GLP-1 agonists (n = 12,351), DPP-4 inhibitors (n = 43,850), or sulfonylureas (n = 32,216) at baseline and were followed for an average of 4.3 years. A total of 4607 dementia cases developed during follow-up: 278 for the GLP-1 agonist initiators (incidence rate: 6.7 per 1000 person years), 1849 for DPP-4 inhibitor initiators (IR: 11.8), and 2480 for sulfonylurea initiators (IR: 13.7). In an intention-to-treat analysis, GLP-1 agonist initiation was associated with a reduced risk of dementia compared to sulfonylureas (hazard ratio: 0.69, 95% CI: 0.60–0.79, p < 0.0001) and DPP-4 inhibitors (HR: 0.77, 95% CI: 0.68–0.88, p < 0.0001), after adjusting for age, enrollment year, sex, socioeconomic factors, health conditions, and past medication uses. These findings were consistent in several sensitivity analyses, including a per-protocol analysis (HR for sulfonylureas: 0.41, 95% CI: 0.32–0.53, p < 0.0001; HR for DPP-4 inhibitors: 0.38, 95% CI: 0.30–0.49, p < 0.0001). Our research suggested that GLP-1 agonists were associated with a lower risk of dementia compared to sulfonylureas and DPP-4 inhibitors in older individuals with T2DM. Further clinical trials are needed to validate these findings. 10.13039/501100004359 Swedish Research Council , 10.13039/501100004047 Karolinska Institutet , the 10.13039/100000049 National Institute on Aging , the 10.13039/100000002 National Institutes of Health , and 10.13039/501100004472 Riksbankens Jubileumsfond .

Background/Objectives: Frailty has been linked to increased risk of COVID‐19 mortality, but evidence is mainly limited to hospitalized older individuals. This study aimed to assess and compare predictive abilities of different frailty and comorbidity measures for COVID‐19 mortality in a community sample and COVID‐19 inpatients. Design: Population‐based cohort study. Setting: Community. Participants: We analyzed (i) the full sample of 410,199 U.K. Biobank participants in England, aged 49–86 years, and (ii) a subsample of 2812 COVID‐19 inpatients with COVID‐19 data from March 1 to November 30, 2020. Measurements: Frailty was defined using the physical frailty phenotype (PFP), frailty index (FI), and Hospital Frailty Risk Score (HFRS), and comorbidity using the Charlson Comorbidity Index (CCI). PFP and FI were available at baseline, whereas HFRS and CCI were assessed both at baseline and concurrently with the start of the pandemic. Inpatient COVID‐19 cases were confirmed by PCR and/or hospital records. COVID‐19 mortality was ascertained from death registers. Results: Overall, 514 individuals died of COVID‐19. In the full sample, all frailty and comorbidity measures were associated with higher COVID‐19 mortality risk after adjusting for age and sex. However, the associations were stronger for the concurrent versus baseline HFRS and CCI, with odds ratios of 20.40 (95% confidence interval = 16.24–25.63) comparing high (>15) to low (0.8. When restricting analyses to COVID‐19 inpatients, similar improvement in AUC was not observed. Conclusion: HFRS and CCI constructed from medical records concurrent with the start of the pandemic can be used in COVID‐19 mortality risk stratification at the population level, but they show limited added value in COVID‐19 inpatients.

Background: DNA methylation-derived epigenetic clocks and frailty are well-established biological age measures capturing different aging processes. However, whether they are dynamically linked to each other across chronological age remains poorly understood. Methods: This analysis included 1 309 repeated measurements in 524 individuals aged 50–90 years from the Swedish Adoption/Twin Study of Aging. Frailty was measured using a validated 42-item frailty index (FI). Five epigenetic clocks were calculated, including 4 principal component (PC)-based clocks trained on chronological age (PCHorvathAge and PCHannumAge) and aging-related physiological conditions (PCPhenoAge and PCGrimAge), and a pace of aging clock (DunedinPACE). Using dual change score models, we examined the dynamic, bidirectional associations between each of the epigenetic clocks and the FI over age to test for potential causal associations. Results: The FI exhibited a nonlinear, accelerated increase across the older adulthood, whereas the epigenetic clocks mostly increased linearly with age. For PCHorvathAge, PCHannumAge, PCPhenoAge, and PCGrimAge, their associations with the FI were primarily due to correlated levels at age 50 but with no evidence of a dynamic longitudinal association. In contrast, we observed a unidirectional association between DunedinPACE and the FI, where a higher DunedinPACE predicted a subsequent increase in the FI, but not vice versa. Conclusions: Our results highlight a temporal order between epigenetic aging and frailty such that changes in DunedinPACE precede changes in the FI. This potentially suggests that the pace of aging clock can be used as an early marker of the overall physiological decline at system level.