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Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

Journal of Biosciences and Medicines 2016年第5期4卷 1-20页

作者： Joaquín Lasierra-Cirujeda María José aza Pascual-Salcedo Alicia Lasierra-Ibañez carmen lasala aza María Mercedes aza Pascual-Salcedo Centro Médico Hematológico Logrono Spain Pharmaceutical Act Ministry of Health La Rioja Regional Government Logrono Spain Aragon Health Service Zaragoza Spain

Aging can be interpreted as an unavoidable process whose end point is the death. Aging entails, in the hemostasis field, some changes that favour blood hypercoagulability. Both the plasminogen activator inhibitor (PAI-1), specific inhibitor of the tissue plasminogen activator (t-PA), accompanied by the oxidative stress and the marked decrease of the main antioxidant—glutathione are fundamental in the bases of elderly pathologies which can cause death. There is some scientific evidence of the relationship between aging, neuro-degenerative diseases, an excessive production of reactive oxygen species and the decrease of proteolysis in brain. The cerebral plasminogen/plasmin system represents the essential proteolytic mechanism that degrades amyloid peptides (β-amyloidosis) for action of plasmin with effectiveness. This physiologic process is being considered as a preventive neurodegenerative mechanism. At the same time, the decrease of glutathione levels in aging entails a decrease of cerebral plasmin activity and a progressive descent of t-PA activity due to a descent in t-PA expression and an increase in PAI production. All of them entail an increment of amyloid beta peptides (Aβ) production and a lower level of their clearance. Both mechanisms, oxidative stress, direct consequence of the oxygenate metabolism of aerobics cells, and changes in the systemic fibrinolysis and cerebral b-amyloidolytic activity, play a very important role in thromboembolic disease, metabolic syndrome—obesity, insulin resistance, hyperglycemia—, type 2 Diabetes Mellitus and Alzheimer’s disease, clinical processes that accompany the aging. In this revision we show the importance of the interaction between glutathione, proteolytic t-PA/plasminogen/plasmin system, and the inhibitor PAI-1 in aging physiopathology, whose results suggest the hypothesis of the importance of a therapeutic strategy using the inhibition of PAI-1 as a goal, because it is increased in the different aging pathologic pro

关键词： Aging Alzheimer’s Disease T2DM PAI-1 Glutathione

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The Physiopathological Crossroads of Aging

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Journal of Biosciences and Medicines 2019年第6期7卷 102-128页

作者： J.Lasierra-Cirujeda P.Coronel M.J.aza pascual-salcedo M.Gimeno M.M.aza Pascual Salcedo A.Lasierra-Ibanez C.lasala-aza logrono(la rioja) spain tedec-meji farma saalcala de henaresmadridspain pharmacy service la rioja health departmentla riojaspain pharmacy service aragon health servicezaragozaspain sciences faculty grade biochemistryuniversity of navarranavarraspain pharmacy faculty university of valenciavalenciaspain

Stress, inflammation and Plasminogen activator inhibitor 1 (PAI-1) are key mechanisms throughout the development of aging, constituting a crossroad in the most frequent pathologies that accompany it. Among metabolic processes, obesity, metabolic syndrome and type 2 diabetes mellitus are included and Alzheimer’s disease among the neurodegenerative processes. Stress is a mechanism of defense of the organism against exogenous and endogenous actions called stressors. In the case of low intensity stimuli, the organism responds with actions aimed at a physiological adaptation (Homeostasis). On the other hand, when a high intensity (experimental level) or chronic stimulus (oxidative stress) is repeated, structural and functional changes are observed in different organs with activation of the hypothalamus-pituitary-adrenal axis, the renin angiotensin system and the sympathetic nervous system, stimulating the production of hormones that release cytokines with proin-flammatory/antiinflammatory properties that play an important role in the previously mentioned pathologies, as well as a marked increase in PAI-1, a gene regulated by stress and by cytokines, with manifest action at the origin of thromboembolic disease, so frequent in aging. The objective of this review is to highlight the importance of the binomial stress and PAI-1 in aging and in the pathologies that accompany it. Because PAI-1 is part of the pathology and complications in aging, some authors suggest the study of PAI-1 inhibitors to achieve its physiological levels, as part of the treatment of these diseases.

关键词： Aging. Oxidative Stress Plasminogen Activator Inhibitor 1 Transforming Growth Factor Beta 1 Glutathione Alzheimer’s Disease

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