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      A possible effect of montelukast on neurological aging examined by the use of register data

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          Abstract

          Background The leukotriene receptor antagonist montelukast has been shown to rejuvenate aged brains in rats; however, data on humans are still scarce. Objective To investigate if montelukast may alleviate degenerative neurological changes using a register data. Setting Norwegian registry data analyses. Method The present observational study was based on data from the Norwegian Prescription Database and the Tromsø Study. The former has information regarding the use of prescription medicine; the latter includes tests for brain function such as subjective memory and finger-tapping. Multivariate linear regression analyses were performed to see how the use of various medications correlated with the test results, correcting for likely confounders. Main outcome measure Results on seven different tests considered relevant for neurological health were used as outcome. Results Previous use of montelukast correlated with improved scores on cognitive or neurological functioning (F = 2.20, p = 0.03 in a multivariate test). A range of other medications were tested with the same algorithm, including drugs acting on the immune system, but none of them correlated with (overall) significantly improved test results. Conclusion The present data suggest that montelukast may alleviate degenerative neurological changes associated with human aging.

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          Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

          Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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            Inflammaging: a new immune–metabolic viewpoint for age-related diseases

            Ageing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation - called inflammaging - develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases.
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              Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.

              Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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                Author and article information

                Contributors
                bjgr@fhi.no
                Journal
                Int J Clin Pharm
                Int J Clin Pharm
                International Journal of Clinical Pharmacy
                Springer International Publishing (Cham )
                2210-7703
                2210-7711
                9 October 2020
                9 October 2020
                2021
                : 43
                : 3
                : 541-548
                Affiliations
                [1 ]GRID grid.418193.6, ISNI 0000 0001 1541 4204, Division of Mental and Physical Health, , Norwegian Institute of Public Health, ; Oslo, Norway
                [2 ]GRID grid.10919.30, ISNI 0000000122595234, Department of Clinical Medicine, , UiT The Arctic University of Norway, ; Tromsø, Norway
                [3 ]GRID grid.412244.5, ISNI 0000 0004 4689 5540, Department of Cardiology, , University Hospital North Norway, ; Tromsø, Norway
                [4 ]GRID grid.10919.30, ISNI 0000000122595234, Department of Community Medicine, , UiT The Arctic University of Norway, ; Tromsø, Norway
                [5 ]GRID grid.21604.31, ISNI 0000 0004 0523 5263, Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, , Paracelsus Medical University, ; Salzburg, Austria
                Author information
                http://orcid.org/0000-0003-1216-2851
                Article
                1160
                10.1007/s11096-020-01160-8
                8214582
                33034810
                044163da-f88c-47d2-a5c3-97e7fb32f5f1
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 April 2020
                : 17 September 2020
                Funding
                Funded by: Norwegian Institute of Public Health (FHI)
                Categories
                Research Article
                Custom metadata
                © Springer Nature Switzerland AG 2021

                Pharmacology & Pharmaceutical medicine
                anti-inflammatory medication,dementia,leukotriene,montelukast,neurological decline,prescription database

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