Age
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A third of those over 80 years of age are likely to have dementia, the lack of a cure requires efforts directed at prevention and delaying the age of onset. We argue here for the importance of understanding the cognitive ageing process, seen as the decline in various cognitive functions from adulthood to old age. The impact of age on cognitive function is heterogeneous and the identification of risk factors associated with adverse cognitive ageing profiles would allow well-targeted interventions, behavioural or pharmacological, to delay and reduce the population burden of dementia. A shift away from binary outcomes such as dementia assessed at one point in time in elderly populations to research on cognitive ageing using repeated measures of cognitive function and starting earlier in the life course would allow the sources of variability in ageing to be better understood.
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Comparative Study
Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice.
The cardiovascular complications reported to be associated with cyclooxygenase inhibitor use have shifted our focus toward prostaglandins and their respective receptors. Prostaglandin D(2) and its DP1 receptor have been implicated in various normal and pathologic conditions, but their role in stroke is still poorly defined. Here, we tested whether DP1 deletion aggravates N-methyl-D: -aspartic acid (NMDA)-induced acute toxicity and whether DP1 pharmacologic activation protects mice from acute excitotoxicity and transient cerebral ischemia. ⋯ The lowest tested dose of BW245C also was able to reduce middle cerebral artery occlusion-induced brain infarction size significantly (21.0 +/- 5.7%). Interestingly, the aggravated NMDA-induced brain damage was persistent in older DP1(-/-) mice as well. We conclude that the DP1 receptor plays an important role in attenuating brain damage and that selective targeting of this receptor could be considered as an adjunct therapeutic tool to minimize stroke damage.
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Comparative Study
Alteration of Aβ metabolism-related molecules in predementia induced by AlCl3 and D-galactose.
The purpose of this study was to look for alterations in β-amyloid peptide (Aβ) metabolism-related molecules in predementia, the early stage of Alzheimer’s disease (AD). AlCl3 (Al) and d-galactose (D-gal) were used to induce the mouse model for predementia and AD. Protein expression of β-amyloid (Aβ), β-secretase (BACE1), neprilysin (NEP), insulin degrading enzyme (IDE) and receptor for advanced glycation end products (RAGE) in the brain was measured. ⋯ IDE increased from day 60 to day 75. There was no change in RAGE. The results suggest that the observed changes in BACE1, NEP and Aβ in predementia might relate to a different stage of the AD-like pathology, which may be developed into useful biomarkers for the diagnosis of very early AD.
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Experimentally restricting dietary calories, while maintaining adequate dietary nutrient content, extends lifespan in phylogenetically diverse species; thus suggesting the existence of conserved pathways which can modify lifespan in response to energy intake. However, in some cases the impact on longevity may depend on the quality of the energy source. In Drosophila, restriction of dietary yeast yields considerable lifespan extension whereas isocaloric restriction of dietary sugar yields only modest extension, indicating that other diet-responsive pathways can modify lifespan in this species. ⋯ All these diet-induced changes were highly significant (log-rank p < 0.0001). Notably, all four diets resulted in considerably longer life spans than those typically reported for flies fed conventional yeast and sugar based diets. Such defined diets can be used to identify lifespan-modifying pathways and specific gene-nutrient interactions in Drosophila.