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

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