The Genetics of Innate Immunity and Inflammation in Ageing, Age-Related Diseases and Longevity

Abstract

Inflammation is a key component of age-related diseases such as atherosclerosis and Alzheimers disease (AD) and genes coding for inflammatory or anti-inflammatory molecules are, therefore, good candidates for influencing the risk of developing these pathologies. Findings discussed in this chapter suggest that different alleles of genes coding for pro-or anti-inflammatory genes may affect individual life-span expectancy by influencing the type and intensity of immune-inflammatory responses against environmental stressors involved in the development of age-related disease. Our immune system has evolved to control pathogens and so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections in earlier life. However, this may have a deleterious effect on cardiovascular and other inflammatory diseases in later life, such that cardiovascular diseases are a late consequence of an evolutionary beneficial pro-inflammatory response programmed to resist infections in earlier life. Genetic polymorphisms responsible for a low inflammatory response might result in an increased chance of a long life-span in an environment with a reduced antigen (i.e., pathogens) load, such as a modern day healthy environment and may also permit a lower grade survivable inflammatory response to atherogenesis and atherosclerosis-related disease. Here, we review the available data in the literature on inflammatory gene polymorphisms in successful and unsuccessful ageing.