Linking RAGE Variations to Longevity
Advanced glycation end-products (AGEs) build up with age in our tissues, gumming together protein machinery and causing chronic inflammation and other bad behavior on the part of cells through the receptor for AGEs, or RAGE. Thus we should probably not be completely surprised to see associations between variations in RAGE and natural variations in longevity. This reinforces the need for AGE-breakers: treatments that can effectively break down and wash out AGEs, removing the harm that they do. Unfortunately few groups are working on this, despite the fact that there is apparently only one important type of AGE in human tissue.
Demographic and social changes in the last decades have resulted in improvements in health and longevity. The survival of elderly people has improved significantly and thus centenarians are becoming the fastest growing population group. Environmental, genetic, and accidental factors have influenced the human life span. Researchers have gained substantial evidence that advanced glycation end products may play an important role in the processes of physiological aging. The aim of the present study was to investigate any differences in the frequencies of -374T/A polymorphism [of the RAGE gene] in subjects aged 90 years or older and in middle-aged individuals.We observed association between the A allele and genotype homozygous for this allele (AA) with a longer life expectancy in the male population. In particular, there was a prevalence of AA genotype and A allele in long-living subjects and a prevalence of the allele T in middle-aged subjects, indicating a possible protective role of the allele A to aging. In conclusion, our results support the hypothesis that longevity is the result of a good functioning of the immune system and a presumable hyper-expression of variants of anti-inflammatory genes of immunity. The differences in the genetic regulation of inflammatory processes may influence the presence of age-related disorders.