Mechanisms of ageing and development
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The strong evidence of metformin use in subjects affected by type 2 diabetes (T2DM) on health outcomes, together with data from pre-clinical studies, has led the gerontological research to study the therapeutic potential of such a drug as a slow-aging strategy. However, despite clinical use for over fifty years as an anti-diabetic drug, the mechanisms of action beyond glycemic control remain unclear. ⋯ Based on the available evidence, we conclude that metformin, as shown in lower organisms and mice, may be effective in humans' longevity. A complete analysis and follow-up of ongoing clinical trials may provide more definitive answers as to whether metformin should be promoted beyond its use to treat T2DM as a drug that enhances both healthspan and lifespan.
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Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease. ⋯ A strong link between vascular risk factors and dementia has been shown, and the association of diet with several vascular and metabolic diseases is well known. Other plausible mechanisms underlying the relationship between diet and cognitive decline, such as inflammation and oxidative stress, have been established. In addition to the traditional etiological pathways, new hypotheses, such as the role of the intestinal microbiome in cognitive function, have been suggested and warrant further investigation.
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Review
What role (if any) does the highly conserved CSB-PGBD3 fusion protein play in Cockayne syndrome?
The PGBD3 piggyBac transposon inserted into CSB intron 5 early in the primate lineage. As a result of alternative splicing, the human CSB gene now encodes three proteins: CSB, a CSB-PGBD3 fusion protein that joins the N-terminal CSB domain to the C-terminal PGBD3 transposase domain, and PGBD3 transposase. The fusion protein is as highly conserved as CSB, suggesting that it is advantageous in health; however, expression of the fusion protein in CSB-null cells induces a constitutive interferon (IFN) response. ⋯ We speculate that the fusion protein interferes with CSB-dependent chromatin remodeling, generating double-stranded RNA (dsRNA) that induces an IFN response through endosomal TLR or cytoplasmic RIG-I and/or MDA5 RNA sensors. We suggest that the fusion protein was fixed in primates because an elevated IFN response may help to fight viral infection. We also speculate that an inappropriate IFN response may contribute to the clinical presentation of CS.
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Selenium (Se) is an essential trace mineral mediating its biological function primarily through selenoproteins. Accumulated lines of evidence indicate important roles of selenoproteins in the maintenance of optimal brain functions via redox regulation. ⋯ Recent advances using genetically manipulated mouse models demonstrate that selenoproteins offer protection against neurodegeneration primarily through redox regulation. Therapies targeting specific selenoproteins influencing redox regulation could delay the onset of neurodisorders, improve quality of life of patients already affected, and perhaps rescue patients with certain diseases by using novel gene therapies.
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Pneumococcal pneumonia is a significant health concern for pediatric, healthy adult, and elderly populations. The newly licensed pneumococcal 7-valent conjugate (diphtheria CRM197 protein) vaccine, Prevnar, and a second generation experimental 9-valent product have demonstrated, for the first time, a clear and significant impact on pneumococcal pneumonia in children. The potential for saccharide-conjugate vaccines to help prevent pneumococcal pneumonia in adult and elderly populations and potential barriers to the introduction of a conjugate vaccine in adults are discussed.