Ageing research reviews
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Ageing research reviews · Jan 2017
ReviewHutchinson-Gilford Progeria Syndrome: A premature aging disease caused by LMNA gene mutations.
Products of the LMNA gene, primarily lamin A and C, are key components of the nuclear lamina, a proteinaceous meshwork that underlies the inner nuclear membrane and is essential for proper nuclear architecture. Alterations in lamin A and C that disrupt the integrity of the nuclear lamina affect a whole repertoire of nuclear functions, causing cellular decline. In humans, hundreds of mutations in the LMNA gene have been identified and correlated with over a dozen degenerative disorders, referred to as laminopathies. ⋯ In patients harboring this mutation, a severe premature aging disease develops during childhood. Interestingly, progerin is also produced in senescent cells and cells from old individuals, suggesting that progerin accumulation might be a factor in physiological aging. Deciphering the molecular mechanisms whereby progerin expression leads to HGPS is an emergent area of research, which could bring us closer to understanding the pathology of aging.
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Hypertension is a highly prevalent condition with numerous health risks, and the incidence of hypertension is greatest among older adults. Traditional discussions of hypertension have largely focused on the risks for cardiovascular disease and associated events. ⋯ Several key mechanisms--including inflammation, oxidative stress, and endothelial dysfunction--are common to biologic aging and hypertension development and appear to have key mechanistic roles in the development of the cardiovascular and collateral risks of late-life hypertension. The objective of the present review is to highlight the multi-dimensional risks of hypertension among older adults and discuss potential strategies for treatment and future areas of research for improving overall care for older adults with hypertension.
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Ageing research reviews · Jan 2016
Review Meta AnalysisDoes transcranial direct current stimulation enhance cognitive and motor functions in the ageing brain? A systematic review and meta- analysis.
The use of transcranial direct current stimulation (tDCS) to enhance cognitive and motor functions has enjoyed a massive increase in popularity. Modifying neuroplasticity via non-invasive cortical stimulation has enormous potential to slow or even reverse declines in functions associated with ageing. The current meta-analysis evaluated the effects of tDCS on cognitive and motor performance in healthy older adults. ⋯ A random effects model meta-analysis revealed a significant overall standardized mean difference equal to 0.53 (SE=0.09; medium heterogeneity: I(2)=57.08%; and high fail-safe: N=448). Five analyses on moderator variables indicated significant tDCS beneficial effects: (a) on both cognitive and motor task performances, (b) across a wide-range of cognitive tasks, (c) on specific brain areas, (d) stimulation offline (before) or online (during) the cognitive and motor tasks. Although the meta-analysis revealed robust support for enhancing both cognitive and motor performance, we outline a number of caveats on the use of tDCS.
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Sepsis refers to the deleterious and non-resolving systemic inflammatory response of the host to microbial infection and is the leading cause of death in intensive care units. The pathogenesis of sepsis is highly complex. ⋯ In the present review, we highlight emerging evidence that supports the notion that extracellular DAMPs act as crucial proinflammatory danger signals. Furthermore, we discuss the potential of a wide array of DAMPs as therapeutic targets in sepsis.
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Ageing research reviews · Nov 2015
ReviewPluripotent stem cells to model Hutchinson-Gilford progeria syndrome (HGPS): Current trends and future perspectives for drug discovery.
Progeria, or Hutchinson-Gilford progeria syndrome (HGPS), is a rare, fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (p. ⋯ In HGPS, progerin accumulates in cells causing progressive molecular defects, including nuclear shape abnormalities, chromatin disorganization, damage to DNA and delays in cell proliferation. Here we report how, over the past five years, pluripotent stem cells have provided new insights into the study of HGPS and opened new original therapeutic perspectives to treat the disease.