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Genetic of Cytokines: a Tool for Understanding Age-Related Diseases. Results of case-control studies performed on Alzheimer’s Disease, Atherosclerosis, Colorectal Carcinoma, Breast Cancer, Gastric Cancer

The ageing of our populations is a direct consequence of a constant and rapid increase of life expectancy in our countries. Epidemiological data estimate for the future an epidemic development of most chronicdegenerative age-related diseases as cardiovascular, neurodegenerative and metabolic disorders and cancers. There is a strong interaction between ageing, age-related diseases and inflammation. Ageing is characterized by a chronic, low-grade inflammatory status, which is under genetic control and appears to be the consequence of lifelong antigenic load. This is responsible for the chronic immune system activation and proinflammatory cytokine production, peculiar of senescence, the process of somatic deterioration at older age. Low-grade elevations in levels of circulating pro-inflammatory cytokines and their receptors, such as TNF-a“, IL-6, IL-1, IL-1Ra and soluble TNF receptors, are strong independent risk factors of morbidity and mortality in the elderly. The cytokines represent an optimum target to study for understanding of correlation between inflammation and age-related diseases. These messengers of inflammation are under genetic control and a huge amount of studies has investigated their genetic variability in pathological conditions, including AD, Atherosclerosis and Cancers.

Mostra/Nascondi contenuto.
5 1. GENERAL INTRODUCTION 1.1 Ageing and Inflammation Relationship between ageing and inflammation is nowadays largely accepted, it is confirmed by involvement of cells and molecules inflammatory in pathogenesis of the main age-related diseases including Atherosclerosis, Alzheimer Disease (AD), Parkinson Disease, Osteoporosis. Indeed, ageing is associated with chronic, low-grade inflammatory activity leading to long-term tissue damage (Bruunsgaard H et al., 2001). This inflammatory status has been defined by the term of “Inflamm- aging”, coined by Franceschi et al., (2000). This is more evident in men than in women. Inflamm-aging, i.e. the up-regulation of a variety of anti- stress responses at the cellular and molecular level is the consequence of the ability of the body to adapt to and counteract the effects of a variety of stressors, which causes the accumulation of molecular and cellular scars (Franceschi & Bonafè, 2003). Reciprocally, controlling inflammatory status may allow successful ageing to be better attained, as is evident in centenarians (Pawelec G et al., 2002; Candore G et al., 2003). They are the best example of successful ageing, because they have escaped all the common age-related disease, including cancer (Franceschi C et al., 1995). As ageing proceeds, mortality forces select the most robust people, who are indeed capable of reaching the extreme limits of the human life span. It has been suggested that up to 25% of the variation in human lifespan is heritable (Herskind AM et al., 1996; Mitchell BD et al., 2001); the rest is due to environmental exposures, accidents and injuries, and

Tesi di Dottorato

Dipartimento: Dipartimento di Biopatologia e Metodol Biomediche

Autore: Antonino Crivello Contatta »

Composta da 119 pagine.

 

Questa tesi ha raggiunto 153 click dal 24/06/2009.

Disponibile in PDF, la consultazione è esclusivamente in formato digitale.