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- Erusalimsky, JD, et al.
(författare)
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In Search of 'Omics'-Based Biomarkers to Predict Risk of Frailty and Its Consequences in Older Individuals: The FRAILOMIC Initiative
- 2016
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Ingår i: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 62:2, s. 182-190
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Tidskriftsartikel (refereegranskat)abstract
- An increase in the number of older people experiencing disability and dependence is a critical aspect of the demographic change that will emerge within Europe due to the rise in life expectancy. In this scenario, prevention of these conditions is crucial for the well-being of older citizens and for the sustainability of our healthcare systems. Thus, the diagnosis and management of conditions like frailty, which identifies the people at the highest risk for developing those adverse outcomes, is of critical relevance. Currently, assessment of frailty relies primarily on measuring functional parameters, which have limited clinical utility. In this viewpoint article, we describe the FRAILOMIC Initiative, an international, large-scale, multi-endpoint, community- and clinic-based research study funded by the European Commission. The aim of the study is to develop validated measures, comprising both classic and ‘omics-based' laboratory biomarkers, which can predict the risk of frailty, improve the accuracy of its diagnosis in clinical practice and provide a prognostic forecast on the evolution from frailty to disability. The initiative includes eight established cohorts of older adults, encompassing >75,000 subjects, most of whom (∼70%) are aged >65 years. Data on function, nutritional status and exercise habits have been collected, and cardiovascular health has been evaluated at baseline. Subjects will be stratified as ‘non-frail' or ‘frail' using Fried's definition, all adverse outcomes of interest will be recorded and differentially expressed biomarkers associated with the risk of frailty will be identified. Genomic, proteomic and transcriptomic investigations will be carried out using array-based systems. As circulating microRNAs in plasma have been identified in the context of senescence, ageing and age-associated diseases, a miRNome-wide analysis will also be undertaken to identify a miRNA-based signature of frailty. Blood concentrations of secreted proteins known to be upregulated significantly in senescent endothelial cells and other hypothesis-driven biomarkers will be measured using ELISAs. The FRAILOMIC Initiative aims to issue a series of interim scientific reports as key results emerge. Ultimately, it is hoped that this study will contribute to the development of new clinical tools, which may help individuals to enjoy an old age that is healthier and free from disability.
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- Rozengurt, E., et al.
(författare)
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Signal transduction in mitogenesis : further evidence for multiple pathways
- 1988
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Ingår i: Cold Spring Harbor Symposia on Quantitative Biology. - : Cold Spring Harbor Laboratory Press (CSHL). - 0091-7451 .- 1943-4456. ; 53, s. 945-954
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Tidskriftsartikel (refereegranskat)abstract
- This extract was created in the absence of an abstract.ExcerptGrowth factors are implicated in a wide variety of physiological and pathological processes, including embryogenesis, hematopoiesis, wound healing, immune responses, atherosclerosis, and neoplasis (Evered et al. 1985; Sporn and Roberts 1986). An important link between growth factors and their receptors and oncogene products has also been established (Heldin and Westermark 1984; Weinstein 1987). Thus, the elucidation of the mechanism of action of growth factors has emerged as one of the fundamental problems in biology and may prove crucial for understanding the unrestrained proliferation of cancer cells.Many studis of growth factors have used cultured fibroblasts, such as 3T3 cells, as a model system. These cells cease to proliferate when they deplete the medium of its growth-promoting activity. Such quiescent cells can be stimulated to reinitiate DNA synthesis and cell division either by replenishing the medium with fresh serum or by the addition of growth factors or pharmacological agents in serum-free...
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