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

Cost Functions From Cross-Section Data—Fact or Fantasy?

Production and cost functions have long been recognized as vital components of economic analyses relating to the individual firm. The U.S. Department of Agriculture, beginning with the pioneering work of T V. J. Spillman, has been a continuing participant in their empiric and theoretical development. Whereas early work emphasized farm production and cost functions, much attention has centered lately on the marketing firm. This attention has brought into sharper focus certain organizational and operating characteristics of plants. With growing interest in the marketing area, the work in the Department expanded to include cooperative research with several State experiment stations. A major such effort has involved the Marketing Economics Division, Economic Research Service, and the California Agricultural Experiment Station. This is the first of three papers prepared for publication in Agricultural Economics Research to reflect some aspects of theoretical and methodological developments in these studies. The following paper comments on, and extends the results of, a statistical analysis of costs in the operation of feed mills developed in a cooperative study with the Iowa Agricultural Experiment Station, and reported in this journal by Richard Phillips in 1956. In a second paper the authors will deal with the possibilities of developing production and cost functions from more detailed analysis of accounting records of individual firms. A third paper will discuss the technique of plant cost synthesis. This report grew out of research in plant cost and efficiency carried on cooperatively by the Marketing Economics Division, Economic Research Service, and the Giannini Foundation of Agricultural E conomics,University of California at Berkeley. The authors are indebted to L. L. Sammet, B. C. French, and D. B. DeLoach of the University of California, and W. F. Finner and V. J. Brensike of the Economic Research Service, U.S. Department of Agriculture, for their helpful suggestions during the preparation of this paper

Negotiating Gender Role Expectations: Rhetorical Leadership and Women in the US Senate

The historical paucity of US women senators has provided little opportunity to study women at one of the highest and most prestigious leadership levels. Through a content analysis of 12 months of public discourse in a variety of media, we explore the rhetorical leadership of women senators as they carry out their elected roles. Results indicate that women senators use significantly less aggressive and more ambivalent speech when compared to political norms, and are less likely to use terms denoting accomplishment, praise and human interest. Overall, our results suggest that women continue to feel the effects of gender stereotypes and expectations in higher levels of political office, and these effects may have important negative implications for perceptions of their leadership and effectiveness

Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities

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