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      Ageing gender-specific "Biomarkers of Homeostasis", to protect ourselves against the diseases of the old age

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          Abstract

          Low-grade inflammatory state causes the development of the principal chronic-degenerative pathologies related with ageing. Consequently, it is required a better comprehension of the physiologic origins and the consequences of the low-grade inflammatory state for the identification of 1) the basic mechanisms that lead to the chronic inflammatory state and, after that, to the progression toward the pathologies and 2) the parallel identification of the prognostic biomarkers typical of these passages. These biomarkers could bring to several improvements in the health quality, allowing an early diagnosis and more effective treatments for: a) the prevention strategies on the healthy population, to assure a healthy longevity and b) the identification of personalized treatment in patients, to assure the benefit of the therapy. For the identification of these biomarkers it is necessary to consider that the ageing processes produce alterations of the physiologic systems and that these modifications compromise the communications between these networks: this state constitutes an obstacle for an appropriate physiologic homeostasis, that plays a fundamental role for the safeguard of the health. It is also to be considered that immune senescence affects both men and women, but it does it in different ways: a sexual dimorphism of immune pathways in the setting of immune response homeostasis is normally present, as we previously underlined. Therefore we hypothesize that, in order to prevent the development of the chronic-degenerative pathologies related with ageing, it is important to identify "Biomarkers of Homeostasis " specific for each gender: these are biologic molecules that should be measurable in a practical and no-invasive way and whose variations can quantify the male and female risk of losing the physiologic system homeostatic capacity. This competence is not only critical in the control of inflammation, but it is also prognostic for the passages from low-grade inflammatory state to the chronic inflammation and to the progression toward the degenerative pathologies. Beginning from the actual results, our intent is 1) to discuss and underline the importance of these new research perspectives in the definition of ageing gender-specific clinical "Biomarkers of Homeostasis" and 2) to propose homeostasis biomarkers, already present in the research results.

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          Most cited references69

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          Aging, Cellular Senescence, and Cancer

          For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action.
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            Sex differences in autoimmune disease.

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              Inflammatory mediators in the elderly.

              Ageing is accompanied by 2-4-fold increases in plasma/serum levels of inflammatory mediators such as cytokines and acute phase proteins. A wide range of factors seems to contribute to this low-grade inflammation, including an increased amount of fat tissue, decreased production of sex steroids, smoking, subclinical infections (e.g. asymptomatic bacteriuria), and chronic disorders such as cardiovascular diseases and Alzheimer's disease. Furthermore, there is some evidence that ageing is associated with a dysregulated cytokine response following stimulation. Several inflammatory mediators such as tumour necrosis factor-alpha and interleukin-6 have the potential to induce/aggravate risk factors in age-associated pathology, providing a positive feedback mechanism. Thus, it is possible that inflammatory mediators constitute a link between life style factors, infections and physiological changes in the process of ageing on the one hand and risk factors for age-associated diseases on the other. Consistent with this, inflammatory mediators are strong predictors of mortality independently of other known risk factors and co-morbidity in elderly cohorts. A direct pathogenetic role of inflammatory mediators would be highly likely if longevity was shown to be associated with cytokine polymorphisms regulating cytokine production. Several studies support indeed this hypothesis but, unfortunately, findings in this area are conflicting, which probably reflects the complexity of the effect of cytokine polymorphisms and their interaction with the lifestyle and sex.
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                Author and article information

                Journal
                Immun Ageing
                Immun Ageing
                Immunity & Ageing : I & A
                BioMed Central
                1742-4933
                2014
                6 February 2014
                : 11
                : 3
                Affiliations
                [1 ]Istituto di Farmacologia Traslazionale (IFT), Consiglio Nazionale delle Ricerche (CNR), Unità Operativa di Supporto (UOS), via G. Carducci, 32 - Rotilio Center, 67100 L'Aquila, Italy
                [2 ]Poliambulatorio “Casa della Salute” Nucleo San Gregorio, Azienda Sanitaria Locale (ASL) di Avezzano-Sulmona-L’Aquila, San Gregorio, AQ, Italy
                [3 ]Facoltà di Medicina, Università Degli Studi G. D’Annunzio, Chieti-Pescara, Italy
                Article
                1742-4933-11-3
                10.1186/1742-4933-11-3
                3923003
                24498974
                8320df29-8279-485c-a04c-4c2d4290ff3a
                Copyright © 2014 Berghella et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 28 April 2013
                : 9 December 2013
                Categories
                Hypothesis

                Immunology
                pathology risk indices,clinical homeostatic biomarkers,gender immune pathways,personalized therapies,immunosenescence,age-related pathologies,prevention programs,inflammation

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