Are zinc-bound metallothionein isoforms (I+II and III) involved in impaired thymulin production and thymic involution during ageing?

BACKGROUND: With advancing age, thymic efficiency shows progressive decline due to thymic involution allowing impaired cell-mediated immunity and the appearance of age-related diseases. The intrinsic cause of thymic involution is still undefined. Chronic inflammation and high glucocorticoids (GCs) may be involved. However, transgenic mice, with increased GC sensitivity and over expression of GC receptors, display delayed age-associated thymic involution. This fact suggests that other substances may affect thymic involution. Among them, both isoforms of metallothioneins (MTs) I+II and III are the major candidates because their increments leads to organ atrophy in constant stress and are induced by IL-6, which increases in ageing. Enhanced MTs in ageing allows constant sequester of zinc ions and no subsequent zinc release leading to low zinc ion bioavailability for thymic efficiency. This sequester is very limited in very old age. Thus, we have investigated the MTmRNA (I+II and III) in the thymus from young, old and very old mice. METHODS: MTmRNA and IL-6mRNA (RT-PCR) in the thymus from different donors were tested. Concomitantly, TECs proliferation, zinc ion bioavailability (ratio total thymulin/active thymulin), thymulin activity and corticosterone were tested from different donors. RESULTS: Both isoforms of MTmRNA and IL-6mRNA increase in old thymus coupled with low zinc ion bioavailability, reduced TECs proliferation, impaired thymulin activity and enhanced plasma corticosterone in comparison with young. Conversely, although the thymus is involuted in very old mice because of no changes in thymus weight in comparison to old mice, reduced MTmRNA, especially MT-I+II isoforms, and low IL6mRNA occur. Concomitantly, good zinc ion bioavailability, maintained TECs proliferation, satisfactory thymulin activity and reduced corticosterone are observed in very old mice. CONCLUSIONS: The concomitant increments by high IL-6 of both MT isoforms in the thymus from old mice may be involved in thymic involution because provoking low zinc ion bioavailability, which is relevant for thymic efficiency. By contrast, the limited increments of MTs by low IL-6 induce good zinc ion bioavailability and satisfactory thymic efficiency in very old mice. Therefore, abnormal increased MTs may provoke complete thymic involution during ageing and the possible appearance of age-related diseases. If their increments are instead limited by low inflammation, healthy ageing and longevity may be reached

Speciation of trace elements in human serum by micro anion exchange chromatography coupled with inductively coupled plasma mass spectrometry

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ЗАСТОСУВАННЯ В СХЕМАХ ЗБАГАЧЕННЯ ТОНКОПОДРІБНЕНОЇ СИРОВИНИ УДОСКОНАЛЕНОГО МАГНІТНОГО ГІДРОЦИКЛОНУ

Проблема та її зв'язок з науковими і практичними задачами. Необхідна ступінь подрібнення руди перед її переробленням визначається характером вкраплення рудних мінералів, використанням різних методів збагачення сиро-вини, вимогами до якості концентратів, послідовністю технологічних процесів, що застосовуються у схемах переробки корисних копалин. Чим тонше кінцева крупність подрібнення руди, тим менше залишається мінеральних зростків і тим більше вірогідність отримання якісних концентратів

Prognosis and Interplay of Cognitive Impairment and Sarcopenia in Older Adults Discharged from Acute Care Hospitals

Sarcopenia and cognitive impairment are associated with an increased risk of negative outcomes, but their prognostic interplay has not been investigated so far. We aimed to investigate the prognostic interaction of sarcopenia and cognitive impairment concerning 12-month mortality among older patients discharged from acute care wards in Italy. Our series consisted of 624 patients (age = 80.1 ± 7.0 years, 56.1% women) enrolled in a prospective observational study. Sarcopenia was defined following the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Cognitive impairment was defined as age- and education-adjusted Mini-Mental State Examination (MMSE) score < 24 or recorded diagnosis of dementia. The study outcome was all-cause mortality during 12-month follow-up. The combination of sarcopenia and cognitive ability was tested against participants with intact cognitive ability and without sarcopenia. Overall, 159 patients (25.5%) were identified as having sarcopenia, and 323 (51.8%) were cognitively impaired. During the follow-up, 79 patients (12.7%) died. After adjusting for potential confounders, the combination of sarcopenia and cognitive impairment has been found associated with increased mortality (HR = 2.12, 95% CI = 1.05-4.13). Such association was also confirmed after excluding patients with dementia (HR = 2.13, 95% CI = 1.06-4.17), underweight (HR = 2.18, 95% CI = 1.03-3.91), high comorbidity burden (HR = 2.63, 95% CI = 1.09-6.32), and severe disability (HR = 2.88, 95% CI = 1.10-5.73). The co-occurrence of sarcopenia and cognitive impairment may predict 1-year mortality in older patients discharged from acute care hospitals

Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry

Cellular senescence is a hallmark of aging and a promising target for therapeutic approaches. The identification of senescent cells requires multiple biomarkers and complex experimental procedures, resulting in increased variability and reduced sensitivity. Here, we propose a simple and broadly applicable imaging flow cytometry (IFC) method. This method is based on measuring autofluorescence and morphological parameters and on applying recent artificial intelligence (AI) and machine learning (ML) tools. We show that the results of this method are superior to those obtained measuring the classical senescence marker, senescence-associated beta-galactosidase (SA-β-Gal). We provide evidence that this method has the potential for diagnostic or prognostic applications as it was able to detect senescence in cardiac pericytes isolated from the hearts of patients affected by end-stage heart failure. We additionally demonstrate that it can be used to quantify senescence “in vivo” and can be used to evaluate the effects of senolytic compounds. We conclude that this method can be used as a simple and fast senescence assay independently of the origin of the cells and the procedure to induce senescence

Zinc-bound metallothioneins and immune plasticity: lessons from very old mice and humans

The capacity of the remodelling immune responses during stress (named immune plasticity) is fundamental to reach successful ageing. We herein report two pivotal experimental models in order to demonstrate the relevance of the immune plasticity in ageing and successful ageing. These two experimental models will be compared with the capacity in remodelling the immune response in human centenarians. With regard to experimental models, one model is represented by the circadian rhythms of immune responses, the other one is the immune responses during partial hepatectomy/liver regeneration (pHx). The latter is suggestive because it mimics the immunosenescence and chronic inflammation 48 h after partial hepatectomy in the young through the continuous production of IL-6, which is the main cause of immune plasticity lack in ageing. The constant production of IL-6 leads to abnormal increments of zinc-bound Metallothionein (MT), which is in turn unable in zinc release in ageing. As a consequence, low zinc ion bioavailability appears for thymic and extrathymic immune efficiency, in particular of liver NKT cells bearing TCR γδ. The remodelling during the circadian cycle and during pHx of zinc-bound MT confers the immune plasticity of liver NKT γδ cells and NK cells in young and very old mice, not in old mice. With regard to human centenarians and their capacity in remodelling the immune response with respect to elderly, these exceptional individuals display low zinc-bound MT associated with: a) satisfactory intracellular zinc ion availability, b) more capacity in zinc release by MT, c) less inflammation due to low gene expression of IL-6 receptor (gp130), d) increased levels of IFN-gamma and number of NKT cell bearing TCR γδ. Moreover, some polymorphisms for MT tested in PBMCs from human donors are related to successful ageing. In conclusion, zinc-bound MT homeostasis is fundamental to confer the immune plasticity that is a condition "sine qua non" to achieve healthy ageing and longevity

Ресурсоэффективные системы в управлении и контроле: взгляд в будущее (т. 2): сборник научных трудов VII Международной конференции школьников, студентов, аспирантов, молодых ученых, 8 -13 октября 2018 г., г. Томск

В сборнике представлены материалы VII Международной конференции школьников, студентов, аспирантов, молодых ученых "Ресурсоэффективные системы в управлении и контроле: взгляд в будущее". Более 500 авторов из 35 вузов, предприятий и научных исследовательских университетов России, ближнего и дальнего зарубежья представили тезисы своих докладов, в которых рассматриваются актуальные проблемы неразрушающего контроля и технической диагностики, внедрения систем менеджмента, качества образования, управления в современной экономике. Материалы предназначены для специалистов, преподавателей, аспирантов и студентов вузов, а также для всех интересующихся проблемами ресурсоэффективных технологий