Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

The impact of fine sediment accumulation on the survival of incubating salmon progeny: Implications for sediment management

This paper draws on results from a recent research programme on the impact of fine sediment transport through catchments to present a case for the development of new approaches to improving the quality of salmonid spawning and incubation habitats. To aid the development of these programmes, this paper summarises the mechanisms by which fine sediment accumulation influences the availability of oxygen (O2) to incubating salmon embryos. The results of the investigation indicate that incubation success is inhibited by: (i) the impact of fine sediment accumulation on gravel permeability and, subsequently, the rate of passage of oxygenated water through the incubation environment; (ii) reduced intragravel O2 concentrations that occur when O2 consuming material infiltrates spawning and incubation gravels; and (iii) the impact of fine particles (clay) on the exchange of O2 across the egg membrane. It is concluded that current granular measures of spawning and incubation habitat quality do not satisfactorily describe the complexity of factors influencing incubation success. Furthermore, an assessment of the trends in fine sediment infiltration indicates that only a small proportion of the total suspended sediment load infiltrates spawning and incubation gravels. This casts doubt over the ability of current catchment-based land use management strategies to adequately reduce fine sediment inputs. <br/

Refinement and re-calibration of a conductiometric standpipe method of assessing interstitial flow velocities

A refinement to the conductiometric standpipe method for determining interstitial flow velocities is described. Three modifications to the original calibration are presented: (i) development of calibration curves for gravels of varying permeability; (ii) statistical validation of a practicable field run time; and (iii) integration of zero velocity flow data to the calibration procedure. These modifications are shown to improve the conductiometric probe’s ability to delineate interstitial flow velocities considered critical to salmonid incubation success. Field deployment of the probe highlighted its practical application for determining interstitial flow velocities in salmonid spawning gravels