Biological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of eight DNA-methylation and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the 2016 wave of the United States Health and Retirement Study (HRS; n=9005). We quantified biological aging from four DNA-methylation “clocks” (Horvath, Hannum, PhenoAge, and GrimAge), a DNA-methylation Pace of Aging (DunedinPoAm), and three blood-chemistry measures (PhenoAge, Klemera-Doubal method Biological Age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical-performance tests, self-reported activities of daily living (ADL) limitations and physician-diagnosed chronic diseases, self-rated health, and survival. DNA-methylation and blood-chemistry quantifications of biological aging were moderately correlated (Pearson-r range 0.1-0.4). GrimAge, DunedinPoAm and all three blood-chemistry measures were associated with healthspan characteristics (e.g. mortality effect-size range HR=1.71-2.32 per SD of biological aging) and showed evidence of more advanced/faster biological aging in Black compared with White participants (Cohen’s d=.4-.5). These measures accounted for 13-95% of Black-White differences in healthspan-related characteristics. Findings suggest that reducing disparities in biological aging can contribute to building health equity.

Background Loneliness and social isolation are emerging public health challenges for aging populations. Methods We followed N=11,302 US Health and Retirement Study (HRS) participants aged 50-95 from 2006-2014 to measure persistence of experiences of loneliness and exposure to social isolation. We tested associations of longitudinal loneliness and social isolation phenotypes with disability, morbidity, mortality, and biological aging through 2018. Results During follow-up, 18% of older adults met criteria for loneliness, with 6% meeting criteria at two or more follow-up assessments. For social isolation, these fractions were 21% and 8%. HRS participants who experienced loneliness and were exposed to social isolation were at increased risk for disease, disability, and mortality. Those experiencing persistent loneliness were at a 57% increased hazard of mortality compared to those who never experienced loneliness. For social isolation, the increase was 28%. Effect-sizes were somewhat larger for counts of prevalent activity limitations and somewhat smaller for counts of prevalent chronic diseases. Covariate adjustment for socioeconomic and psychological risks attenuated but did not fully explain associations. Older adults who experienced loneliness and were exposed to social isolation also exhibited physiological indications of advanced biological aging (Cohen’s-d for persistent loneliness and social isolation=0.26 and 0.21, respectively). For loneliness, but not social isolation, persistence was associated with increased risk. Conclusion Deficits in social connectedness prevalent in a national sample of US older adults were associated with morbidity, disability, and mortality and with more advanced biological aging. Bolstering social connectedness to interrupt experiences of loneliness may promote healthy aging.

Background Treatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED). Aim The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE; composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality. Methods A retrospective observational cohort study was conducted in a large US claims database in men with ≥1 diagnosis of ED without prior MACE within 1 year, from January 1, 2006, to October 31, 2020. The exposed group had ≥1 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 1:4 on baseline risk variables. Outcome The primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling. Results Matched plus multivariable analyses showed that MACE was lower by 13% in men exposed (n = 23 816) to PDE-5is (hazard ratio [HR] 0.87; 95% CI 0.79-0.95; P = .001) vs nonexposure (n = 48 682) over mean follow-up periods of 37 and 29 months, respectively, with lower incidence of coronary revascularization (HR 0.85; 95% CI 0.73-0.98; P = .029), heart failure (HR 0.83; 95% CI 0.72-0.97; P = .016), unstable angina (HR 0.78; 95% CI 0.64-0.96; P = .021), and CV death (HR 0.61; 95% CI 0.41-0.90; P = .014) with PDE-5i exposure. Phosphodiesterase type 5 inhibitor–exposed men had a 25% lower incidence of overall mortality (HR 0.75; 95% CI 0.65-0.87; P < .001). Men without coronary artery disease (CAD) but with CV risk factors at baseline showed a similar pattern. In the main study cohort, men in the highest quartile of PDE-5i exposure had the lowest incidence of MACE (HR 0.45; 95% CI 0.37-0.54; P < .001) and overall mortality (HR 0.51; 95% CI 0.37-0.71; P < .001) vs the lowest exposure quartile. In a subgroup with baseline type 2 diabetes (n = 6503), PDE-5i exposure was associated with a lower MACE risk (HR 0.79; 95% CI 0.64-0.97; P = .022). Clinical Implications PDE-5is may have cardioprotective effects. Strengths and Limitations Strengths are the large numbers of participants and consistency of the data; limitations include the retrospective nature of the study and unknown confounders. Conclusions In a large population of US men with ED, PDE-5i exposure was associated with lower incidence of MACE, CV death, and overall mortality risk compared to non-exposure. Risk reduction correlated with PDE-5i exposure level.

Background and Objectives Balancing both driver mobility and safety is important for the well-being of older adults. However, research on the association of physical function with these 2 driving outcomes has yielded inconsistent findings. This study examined whether physical functioning of older drivers, as measured by the Short Physical Performance Battery (SPPB), is associated with either driving space or crash involvement. Methods Using cross-sectional data of active drivers aged 65–79 years from the AAA Longitudinal Research on Aging Drivers (LongROAD) study (n = 2,990), we used multivariate log-binomial and logistic regressions to estimate the associations of the SPPB with either self-reported restricted driving space in the prior 3 months or any crashes in the past year. Interaction with gender was assessed using likelihood ratio tests. Results After adjustment, older drivers with higher SPPB scores (higher physical functioning) had lower prevalence of restricted driving space (8–10 vs. 0–7, prevalence ratio [PR] = 0.88, 95% confidence interval [CI]: 0.78–0.99; 11–12 vs. 0–7, PR = 0.78, 95% CI: 0.61–0.99). Fair (8–10), but not good (11–12), scores were significantly associated with reduced crash involvement (8–10 vs. 0–7, odds ratio [OR] = 0.71, 95% CI: 0.60–0.84). Gender was not a significant effect modifier. Discussion and Implications This study provides evidence that higher physical functioning is associated with better driving mobility and safety and that the SPPB may be useful for identifying at-risk drivers. Further research is needed to understand physical functioning’s longitudinal effects and the SPPB’s role in older driver intervention programs.

The US older adult population is projected to considerably increase in the future, and continued driving mobility is important for health aspects in populations with fewer transportation alternatives. This study evaluated whether frailty is associated with low-mileage driving (<1865 miles per year) and driving cessation among older adults. Baseline demographics and health data were collected for 2990 older drivers via in-person assessments and questionnaires, with 2964 reporting baseline frailty data. Multivariable log-binomial regression models were used to evaluate the association between baseline frailty status and low-mileage driving. Multivariable Cox proportional hazards regression were used to evaluate the association between baseline frailty status and driving cessation. For every unit increase in frailty, the estimated adjusted risk of driving fewer than 1865 miles/year increased by 138% (adjusted risk ratio: 2.38, 95% CI: 1.63-3.46). Relative to older drivers who were not frail, the adjusted hazard ratios of driving cessation were 4.15 (95% CI: 1.89-9.10) for those classified as prefrail and 6.08 (95% CI: 1.36-27.26) for those classified as frail. Frailty is positively associated with low-mileage driving status and driving cessation in a dose-response fashion. Public health interventions that reduce frailty, such as physical activity, may help older drivers maintain safe and independent mobility.