Before getting into the question of core architecture and genetic instability, I'd like to take a few moments to look back at the end of last week's lecture, which I rushed through for lack of time.
Let me remind you (DIA IV.2) that in Drosophila, aging is accompanied by the induction of retrotransposon expression, whether LTR retrotransposons (like gypsy) or more classical retrotransposons like LINEs, and that this expression is accompanied by a drop in behavioral performance and an increase in mortality, especially when Argonaute is inactivated, which reduces the repressive activity of piRNAs (DIA IV.3).
But obviously these are just flies, and I'll close this section with work from the same group on humans and mice (Li et al., PLOS One 7, 9, e4409, 2012). Starting from the finding that the expression of specific transposable elements (TEs) has been observed in several neurodegenerative-type disorders, the authors demonstrated that many of the transposable element transcripts bind to an RNA-binding protein called TAR DNA-binding protein 43 (TDP-43) which plays a role in amyotrophic lateral sclerosis (ALS) and fronto-temporal degeneration (FTLD). Hence the following experiments and hypothesis on the role of TEs and their repression in the regulation of neurodegeneration and aging in mammals.
