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.

CONTEXT: Given the wide-ranging health impacts of justice system involvement, we examined evidence for the association between adverse childhood experiences (ACEs) and justice system contact in the United States. OBJECTIVE: To synthesize epidemiological evidence for the association between ACEs and justice system contact. DATA SOURCES: We searched 5 databases for studies conducted through January 2020. The search term used for each database was as follows: (“aces” OR “childhood adversities”) AND (“delinquency” OR “crime” OR “juvenile” OR criminal* OR offend*). STUDY SELECTION: We included all observational studies assessing the association between ACEs and justice system contact conducted in the United States. DATA EXTRACTION: Data extracted from each eligible study included information about the study design, study population, sample size, exposure and outcome measures, and key findings. Study quality was assessed by using the Newcastle-Ottawa Scale for nonrandomized trials. RESULTS: In total, 10 of 11 studies reviewed were conducted in juvenile population groups. Elevated ACE scores were associated with increased risk of juvenile justice system contact. Estimates of the adjusted odds ratio of justice system contact per 1-point increase in ACE score ranged from 0.91 to 1.68. Results were consistent across multiple types of justice system contact and across geographic regions. LIMITATIONS: Most studies reviewed were conducted in juvenile justice-involved populations with follow-up limited to adolescence or early adulthood. CONCLUSIONS: ACEs are positively associated with juvenile justice system contact in a dose-response fashion. ACE prevention programs may help reduce juvenile justice system contacts and improve child and adolescent health.

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.

The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan1–3. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm)5–7, and is established to increase healthy lifespan in multiple species8,9. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health11–13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14–16 and contrasting with reports that biological aging may not be modifiable17. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality18–20.

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 United States Health and Retirement Study (HRS; n=8231). 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 tests of physical-performance, self-reported limitations to activities of daily living (ADLs), and physician-diagnosed chronic diseases. 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 (10-25% increase in risk per SD of biological aging) and showed evidence of more advanced/faster biological aging in Black compared with White participants (Cohen's d=.3-.5). In mediation analysis, these measures accounted for 19-48% of Black-White differences in healthspan-related characteristics. Evidence that Black Americans are both biologically older and aging more rapidly than White Americans of the same chronological age suggests that differences in aging may represent a novel pathway to understand and eliminate health disparities.

Lower socioeconomic status is associated with faster biological aging, the gradual and progressive decline in system integrity that accumulates with advancing age. Efforts to promote upward social mobility may therefore extend healthy lifespan. However, recent studies suggest that upward mobility may also have biological costs related to the stresses of crossing social boundaries. We tested associations of life-course social mobility with biological aging using data from participants in the 2016 Health and Retirement Study (HRS) Venous Blood Study who provided blood-chemistry (n = 9,255) and/or DNA methylation (DNAm) data (n = 3,976). We quantified social mobility from childhood to later-life using data on childhood family characteristics, educational attainment, and wealth accumulation. We quantified biological aging using three DNA methylation “clocks” and three blood-chemistry algorithms. We observed substantial social mobility among study participants. Those who achieved upward mobility exhibited less-advanced and slower biological aging. Associations of upward mobility with less-advanced and slower aging were consistent for blood-chemistry and DNAm measures of biological aging and were similar for men and women and for Black and White Americans (Pearson-r effect-sizes ∼0.2 for blood-chemistry measures and the DNAm GrimAge clock and DunedinPoAm pace-of-aging measures; effect-sizes were smaller for the DNAm PhenoAge clock). Analysis restricted to educational mobility suggested differential effects by racial identity; mediating links between educational mobility and healthy aging may be disrupted by structural racism. In contrast, mobility producing accumulation of wealth appeared to benefit White and Black Americans equally, suggesting economic intervention to reduce wealth inequality may have potential to heal disparities in healthy aging.

Adverse childhood experiences (ACEs) can affect development in ways that disrupt the formation of human capital and contribute to later-life morbidity and mortality. Theories of development predict that the timing of adversity will affect its outcomes. However, empirical evidence for timing-specific effects remains scant. In this issue of JAMA Network Open, Andersen 1 reports an analysis of population-register data from Denmark that suggests timing-specific associations of household dysfunction ACEs with young people's successful transition to adulthood. Andersen's study 1 linked data from several Danish registers to compose records tracking children born between 1987 and 1995 and their families from the child's birth until they reached age 19 years. The analysis tested how exposure to household dysfunction ACEs during ages 0 to 2, 3 to 5, 6 to 12, and 13 to 17 years were associated with disruptions in children's transition to adulthood. Children's ACE exposure was measured from records of parental unemployment, incarceration, psychiatric diagnoses, and divorce as well as children's placement in foster care. Disruption to the transition to adulthood was measured from records of education, employment, criminal charges, and psychiatric diagnoses. Andersen's

Lower socioeconomic status is associated with faster biological aging, the gradual and progressive decline in system integrity that accumulates with advancing age. Efforts to promote upward social mobility may therefore extend healthy lifespan. However, recent studies suggest that upward mobility may also have biological costs related to the stresses of crossing social boundaries. We analyzed blood-chemistry and DNA methylation (DNAm) data from n=9286 participants in the 2016 Health and Retirement Study (HRS) Venous Blood Study to test associations of life-course social mobility with biological aging. We quantified social mobility from childhood to later-life using data on childhood family characteristics, educational attainment, and wealth accumulation. We quantified biological aging using three DNA methylation "clocks" and three blood-chemistry algorithms. We observed substantial social mobility among study participants. Those who achieved upward mobility exhibited less-advanced and slower biological aging. Associations of upward mobility with less-advanced and slower aging were consistent for blood-chemistry and DNAm measures of biological aging and were similar for men and women and for Black and White Americans (Pearson-r effect-sizes ~0.2 for blood-chemistry measures and the DNAm GrimAge clock and DunedinPoAm pace-of-aging measures; effect-sizes were smaller for the DNAm PhenoAge clock). Analysis restricted to educational mobility revealed differential effects by racial identity, suggesting that mediating links between educational mobility and healthy aging may be disrupted by structural racism. In contrast, mobility producing accumulation of wealth appeared to benefit White and Black Americans equally, suggesting economic intervention to reduce wealth inequality may have potential to heal disparities in healthy aging.