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  1. Article ; Online: Interconnections between Inflammageing and Immunosenescence during Ageing

    Thibault Teissier / Eric Boulanger / Lynne S. Cox

    Cells, Vol 11, Iss 359, p

    2022  Volume 359

    Abstract: Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately lead to the recruitment of immune cells to clear invading pathogens and heal wounds. However, chronic inflammation arising from the continued ... ...

    Abstract Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately lead to the recruitment of immune cells to clear invading pathogens and heal wounds. However, chronic inflammation arising from the continued presence of the initial trigger, or the dysfunction of signalling and/or effector pathways, is harmful to health. While successful ageing in older adults, including centenarians, is associated with low levels of inflammation, elevated inflammation increases the risk of poor health and death. Hence inflammation has been described as one of seven pillars of ageing. Age-associated sterile, chronic, and low-grade inflammation is commonly termed inflammageing—it is not simply a consequence of increasing chronological age, but is also a marker of biological ageing, multimorbidity, and mortality risk. While inflammageing was initially thought to be caused by “continuous antigenic load and stress”, reports from the last two decades describe a much more complex phenomenon also involving cellular senescence and the ageing of the immune system. In this review, we explore some of the main sources and consequences of inflammageing in the context of immunosenescence and highlight potential interventions. In particular, we assess the contribution of cellular senescence to age-associated inflammation, identify patterns of pro- and anti-inflammatory markers characteristic of inflammageing, describe alterations in the ageing immune system that lead to elevated inflammation, and finally assess the ways that diet, exercise, and pharmacological interventions can reduce inflammageing and thus, improve later life health.
    Keywords ageing ; inflammation ; cytokines ; inflammageing ; immunosenescence ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Structural basis of the anti-ageing effects of polyphenolics

    Adam Rolt / Lynne S. Cox

    BMC Chemistry, Vol 14, Iss 1, Pp 1-

    mitigation of oxidative stress

    2020  Volume 13

    Abstract: Abstract Ageing, and particularly the onset of age-related diseases, is associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Polyphenolic natural products such as stilbenoids, ... ...

    Abstract Abstract Ageing, and particularly the onset of age-related diseases, is associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Polyphenolic natural products such as stilbenoids, flavonoids and chalcones have been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis and cellular senescence, both in vitro and in vivo. Here we aim to identify the structural basis underlying the pharmacology of polyphenols towards ROS and related biochemical pathways involved in age-related disease. We compile and describe SAR trends across different polyphenol chemotypes including stilbenoids, flavonoids and chalcones, review their different molecular targets and indications, and identify common structural ground between chemotypes and mechanisms of action. In particular, we focus on the structural requirements for the direct scavenging of reactive oxygen/nitrogen species such as radicals as well as coordination of a broader antioxidant response. We further suggest that it is important to consider multiple (rather than single) biological activities when identifying and developing new medicinal chemistry entities with utility in modulating complex biological properties such as cell ageing.
    Keywords Ageing ; Aging ; Oxidative stress ; Inflammation ; Antioxidants ; Polyphenols ; Chemistry ; QD1-999
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  3. Article ; Online: mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases

    Hannah E. Walters / Lynne S. Cox

    International Journal of Molecular Sciences, Vol 19, Iss 8, p

    2018  Volume 2325

    Abstract: Chronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual ... ...

    Abstract Chronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing, and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR (mechanistic target of rapamycin) is a regulatory nexus that is heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.
    Keywords mTOR ; mTORC1 ; mTORC2 ; rapamycin ; rapalogues ; rapalogs ; mTOR inhibitors ; senescence ; ageing ; aging ; cancer ; neurodegeneration ; immunosenescence ; senolytics ; biomarkers ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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