Apolipoprotein E is a Longevity-Associated Gene

It remains unclear as to why apolipoprotein E (APOE) variants are associated with longevity in humans. The gene has a well-studied role in Alzheimer's disease, but the reasons why APOE variants are associated with aging remain to be determined. The most likely mechanisms involve (a) interactions with age-related disruptions of lipid metabolism, both in the brain and elsewhere, and (b) indirect effects on the inflammatory behavior of innate immune cells such as microglia. There are plenty of other interactions to further study, however, such as in bone tissue, or effects on the gut microbiome. As is often the case, a great deal of data exists, but making sense of that data lags far behind the ability to generate more of it. The APOE variants, respectively ε2 ε3, ε4, and ε3r, are determined by four haplotypes at the APOE locus (19q13.32). These four APOE alleles are probably the most investigated variants in the human genome. Remarkably, the APOE exon 4 region, encompassing the ε2/ε3/ε4 allele variants, is a well-defined CpG islands-rich area. Moreover, the two common SNPs rs429358 and rs7412 are CpG-altering and modify the CpG content of this area. This APOE CpG island-rich area is a transcriptional enhancer with a specificity linked to the ε4 allele and cell-type. A genetic association of APOE with both human longevity and Alzheimer's disease (AD) was found, but the mechanistic contribution of APOE in aging and long life is largely under investigation....
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs