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Sökning: WFRF:(Finkel D)

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  • Aad, G, et al. (författare)
  • 2015
  • swepub:Mat__t
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  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Zammit, A. R., et al. (författare)
  • A Coordinated Multi-study Analysis of the Longitudinal Association Between Handgrip Strength and Cognitive Function in Older Adults
  • 2021
  • Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press (OUP). - 1758-5368 .- 1079-5014. ; 76:2, s. 229-241
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Handgrip strength, an indicator of overall muscle strength, has been found to be associated with slower rate of cognitive decline and decreased risk for cognitive impairment and dementia. However, evaluating the replicability of associations between aging-related changes in physical and cognitive functioning is challenging due to differences in study designs and analytical models. A multiple-study coordinated analysis approach was used to generate new longitudinal results based on comparable construct-level measurements and identical statistical models and to facilitate replication and research synthesis. METHODS: We performed coordinated analysis on 9 cohort studies affiliated with the Integrative Analysis of Longitudinal Studies of Aging and Dementia (IALSA) research network. Bivariate linear mixed models were used to examine associations among individual differences in baseline level, rate of change, and occasion-specific variation across grip strength and indicators of cognitive function, including mental status, processing speed, attention and working memory, perceptual reasoning, verbal ability, and learning and memory. Results were summarized using meta-analysis. RESULTS: After adjustment for covariates, we found an overall moderate association between change in grip strength and change in each cognitive domain for both males and females: Average correlation coefficient was 0.55 (95% CI = 0.44-0.56). We also found a high level of heterogeneity in this association across studies. DISCUSSION: Meta-analytic results from nine longitudinal studies showed consistently positive associations between linear rates of change in grip strength and changes in cognitive functioning. Future work will benefit from the examination of individual patterns of change to understand the heterogeneity in rates of aging and health-related changes across physical and cognitive biomarkers. Published by Oxford University Press on behalf of The Gerontological Society of America 2019.
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  • Duggan, E. C., et al. (författare)
  • A Multi-study Coordinated Meta-analysis of Pulmonary Function and Cognition in Aging
  • 2019
  • Ingår i: Journals of Gerontology Series a-Biological Sciences and Medical Sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 74:11, s. 1793-1804
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Substantial research is dedicated to understanding the aging-related dynamics among Methods: We performed coordinated analysis of bivariate growth models in data from 20,586 Results: We found consistent but weak baseline and longitudinal associations in levels of pulmonary Conclusions: Results provide limited evidence for a consistent link between simultaneous changes in
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