Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al. 2020). Here we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).Methods: We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

The electronic band structure of a semiconductor photocatalyst intrinsically controls its level of conduction band (CB) and valence band (VB) and, thus, influences its activity for different photocatalytic reactions. Here, we report a simple bottom-up strategy to rationally tune the band structure of graphitic carbon nitride (g-C3N4). By incorporating electron-deficient pyromellitic dianhydride (PMDA) monomer into the network of g-C3N4, the VB position can be largely decreased and, thus, gives a strong photooxidation capability. Consequently, the modified photocatalyst shows preferential activity for water oxidation over water reduction in comparison with g-C3N4. More strikingly, the active species involved in the photodegradation of methyl orange switches from photogenerated electrons to holes after band structure engineering. This work may provide guidance on designing efficient polymer photocatalysts with the desirable electronic structure for specific photoreactions.

The current study investigated the cognitive deficit profiles among individuals with mathematics difficulties (MD) and potential moderators and mechanism for these profiles. Seventy-five cognitive profiling studies on MD were included, representing a total of 13,001 individuals and 126 independent samples. Results showed that compared with typically developing individuals, individuals with MD showed deficits (from most severe to less severe) in phonological processing, processing speed, working memory, attention, short-term memory, executive functions, and visuospatial skills. Moderation analyses indicated that comorbidity (with reading disabilities) and types of MD screening affected the cognitive deficits. Severity of MD was related to processing speed deficits. Deficits in phonological processing and attention were more severe in younger individuals with MD. Deficits in processing speed and working memory were most severe in the numerical domain. Deficits in low-level cognitive skills (i.e., processing speed and short-term memory) could not completely explain the deficits in high-level skills (i.e., working memory, attention, and executive functions), partially supporting the bottleneck theory. These findings, taken together, suggest that (a) deficits in processing speed and working memory are most salient and stable cognitive markers of MD, (b) numerical-processing deficit and the cognitive deficits of MD are relatively independent from each other, and (c) MD may be a discrete construct with heterogeneity reflected by MD subtypes and age. Implications for incorporating cognition in the diagnosis and the interventions for MD are discussed.