DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function

Background The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E−03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang’s 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β =  − 0.12, 95% CI = [− 0.16, − 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E−08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E−06). The “first-generation” clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease

Environmentally Just Futures: A Collection of Community-Driven African Environmental Education and Improvement Initiatives

Advocating for healthy environments is a matter of justice. Changes in environments have tremendous impacts on the health of communities, and oftentimes, individuals are unable to safeguard themselves through individual actions alone. Efforts frequently require collective action and are often most effective when led by the communities most impacted. In this spirit, we launched &ldquo;Vibrations&rdquo;, an African environment photo essay contest. Through funding and publicity, we aimed to support community-led environmental improvement and education initiatives presently taking place on the continent. We received nearly two dozen submissions and selected eight winners. The winners come from five countries (Ghana, Kenya, Mozambique, Nigeria, and South Africa) and have taken on a range of projects aimed at improving environments across a variety of African regions. Projects included efforts to combat pollution, create environmentally conscious school curricula, utilize clean energy sources, and spread awareness about environmental justice concerns in local communities. It is our hope that this report highlights these transformative community-driven efforts, promotes continued conversations on environmental justice in Africa, and encourages meaningful action via policy changes and collaborations throughout the African continent and beyond

Polypharmacy Exposure, Aging Populations, and COVID-19: Considerations for Healthcare Providers and Public Health Practitioners in Africa

Given the continent’s growing aging population and expanding prevalence of multimorbidity, polypharmacy is an increasingly dire threat to the health of persons living in Africa. The COVID-19 pandemic has only exacerbated these issues. Widespread misinformation, lack of vaccine access, and attempts to avoid being infected have resulted in increases in Africans’ willingness to take multiple prescription and nonprescription medications and supplements. Issues with counterfeit pharmaceuticals and the relatively new recognition of emergency medicine as a specialty across the continent also create unique challenges for addressing this urgent public health need. Experts have called for more robust pharmaceutical regulation and healthcare/public health infrastructure investments across the continent. However, these changes take time, and more near-term strategies are needed to mitigate current health needs. In this commentary, we present a nonexhaustive set of immediately implementable recommendations that can serve as local strategies to address current polypharmacy-related health needs of Africans. Importantly, our recommendations take into consideration that not all healthcare providers are emergency medicine trained and that local trends related to polypharmacy will change over time and require ever-evolving public health initiatives. Still, by bolstering training to safeguard against provider availability biases, practicing evidence-based prescribing and shared decision making, and tracking and sharing local trends related to polypharmacy, African healthcare providers and public health practitioners can better position themselves to meet population needs. Furthermore, although these recommendations are tailored to Africans, they may also prove useful to providers and practitioners in other regions facing similar challenges

A Longitudinal Epigenetic Aging and Leukocyte Analysis of Simulated Space Travel: The Mars-500 Mission.

Astronauts undertaking long-duration space missions may be vulnerable to unique stressors that can impact human aging. Nevertheless, few studies have examined the relationship of mission duration with DNA-methylation-based biomarkers of aging in astronauts. Using data from the six participants of the Mars-500 mission, a high-fidelity 520-day ground simulation experiment, we tested relationships of mission duration with five longitudinally measured blood DNA-methylation-based metrics: DNAmGrimAge, DNAmPhenoAge, DNA-methylation-based estimator of telomere length (DNAmTL), mitotic divisions (epigenetic mitotic clock [epiTOC2]), and pace of aging (PoA). We provide evidence that, relative to baseline, mission duration was associated with significant decreases in epigenetic aging. However, only decreases in DNAmPhenoAge remained significant 7&nbsp;days post-mission. We also observed significant changes in estimated proportions of plasmablasts, CD4T, CD8 naive, and natural killer (NK) cells. Only decreases in NK cells remained significant post-mission. If confirmed more broadly, these findings contribute insights to improve the understanding of the biological aging implications for individuals experiencing long-duration space travel