Immunogenetics of ageing

The ageing process is very complex. Human longevity is a multifactorial trait which is determined by genetic and environmental factors. Twin and family studies imply that up to 25% of human lifespan is heritable. The longevity gene candidates have generally fallen into the following categories: inflammatory and immune‐related factors, stress response elements, mediators of glucose and lipid metabolism, components of DNA repair and cellular proliferation and mitochondrial DNA haplogroups. Because of the central role of HLA molecules in the development of protective immunity and the extraordinary degree of polymorphism of HLA genes, many studies have addressed the possible impact of these genes on human longevity. Most of the data available so far demonstrated a possible role of HLA class II specificities in human longevity but definitive evidence has remained elusive. Although the data are limited and controversial, it has been hypothesized that longevity could be associated with cytokine gene polymorphisms correlating with different levels of cytokine production, thereby modulating immune responses in health and disease. Because of the essential role of cytokines in immune responses, the regulation of cytokine gene expression and their polymorphic nature, the genetic variations of these loci with functional significance could be appropriate immunogenetic candidate markers implicated in the mechanism of successful ageing and longevity. In addition, several other genes such as Toll‐like receptor genes, Cycloxygenases (COX)/Lipoxygenases (LOX), CCR5, NK receptor genes and MBL2 have been assessed as a possible biomarkers associated with ageing. This review will summarize the data on the role of these immune genes in human longevity.

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