The Retrotransposon storm and the dangers of a Collyer's genome.

Like the famous Collyer's mansion in NY, our genomes have accumulated vast quantities of sequences that have been referred to as 'junk DNA,' much of which consists of retrotransposons (RTEs). A recent literature establishes the phenomenology that many RTEs become expressed at progressively higher levels during the course of normal aging. This seems to reflect gradual loss of heterochromatin in old age. In addition, RTEs appear to be precociously expressed in brains of younger animals that are experiencing neurodegenerative decline. Although it is difficult to distinguish cause from consequence, several recent studies support the contention that RTE expression, and even perhaps transposition, causally contribute to both the normal deterioration seen with age and to the precipitous decline in some neurodegenerative disorders. This may reflect a two hit model in which normal age-dependent loss of heterochromatin synergizes with a disruption to posttranscriptional silencing of RTEs caused by genetic and environmental stress.