The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up

The VLA Nascent Disk And Multiplicity (VANDAM) Survey of Perseus Protostars. Resolving the Sub-Arcsecond Binary System in NGC 1333 IRAS2A

We are conducting a Jansky VLA Ka-band (8 mm and 1 cm) and C-band (4 cm and 6.4 cm) survey of all known protostars in the Perseus Molecular Cloud, providing resolution down to $\sim$0.06'' and $\sim$0.35" in Ka-band and C-band, respectively. Here we present first results from this survey that enable us to examine the source NGC 1333 IRAS2A in unprecedented detail and resolve it into a proto-binary system separated by 0.621"$\pm$0.006" ($\sim$143 AU) at 8 mm, 1 cm, and 4 cm. These 2 sources (IRAS2A VLA1 and VLA2) are likely driving the two orthogonal outflows known to originate from IRAS2A. The brighter source IRAS2A VLA1 is extended perpendicular to its outflow in the VLA data, with a deconvolved size of 0.055" ($\sim$13 AU), possibly tracing a protostellar disk. The recently reported candidate companions (IRAS2A MM2 and MM3) are not detected in either our VLA data, CARMA 1.3 mm data, or SMA 850 $\mu$m data. SMA CO ($J=3\rightarrow2$), CARMA CO ($J=2\rightarrow1$), and lower resolution CARMA CO ($J=1\rightarrow0$) observations are used to examine the outflow origins and the nature of the candidate companions to IRAS2A VLA1. The CO ($J=3\rightarrow2$) and ($J=2\rightarrow1$) data show that IRAS2A MM2 is coincident with a bright CO emission spot in the east-west outflow, and IRAS2A MM3 is within the north-south outflow. In contrast, IRAS2A VLA2 lies at the east-west outflow symmetry point. We propose that IRAS2A VLA2 is the driving source of the East-West outflow and a true companion to IRAS2A VLA1, whereas IRAS2A MM2 and MM3 may not be protostellar.Comment: Accepted to ApJ, 27 pages, 6 Figures, 2 Table

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regulatory associations with cortical substrates of cognition. We find that the region-to-region variation in cortical expression profiles of 8235 genes covaries across two major principal components: gene ontology analysis suggests these dimensions are characterised by downregulation and upregulation of cell-signalling/modification and transcription factors. We validate these patterns out-of-sample and across different data processing choices. Brain regions more strongly implicated in general cognitive functioning (g; 3 cohorts, total meta-analytic N = 39,519) tend to be more balanced between downregulation and upregulation of both major components (indicated by regional component scores). We then identify a further 29 genes as candidate cortical spatial correlates of g, beyond the patterning of the two major components (|β| range = 0.18 to 0.53). Many of these genes have been previously associated with clinical neurodegenerative and psychiatric disorders, or with other health-related phenotypes. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regulatory associations with cortical substrates of cognition. We find that the region-to-region variation in cortical expression profiles of 8235 genes covaries across two major principal components: gene ontology analysis suggests these dimensions are characterised by downregulation and upregulation of cell-signalling/modification and transcription factors. We validate these patterns out-of-sample and across different data processing choices. Brain regions more strongly implicated in general cognitive functioning (g; 3 cohorts, total meta-analytic N = 39,519) tend to be more balanced between downregulation and upregulation of both major components (indicated by regional component scores). We then identify a further 29 genes as candidate cortical spatial correlates of g, beyond the patterning of the two major components (|β| range = 0.18 to 0.53). Many of these genes have been previously associated with clinical neurodegenerative and psychiatric disorders, or with other health-related phenotypes. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning

We thank the participants of the three cohorts (UKB, Generation Scotland (STRADL) and LBC1936) for their participation and the research teams for their work in collecting, processing and giving access to these data for analysis. We are also thankful to the brain donors to the Allen Human Brain Atlas, BrainSpan Atlas and Human Brain Transcriptome Project, and to the people who collected and processed the data and made it openly available For the purpose of open access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewe