• epigenetic
• autism
• aging

Numerous lines of evidence support the notion that epigenetic changes directly contribute to aging and aging-related diseases. Deciphering the molecular mechanisms underlying the activity of epigenetic regulators in the context of aging represents therefore a crucial step in the comprehension of this important biological process.
SETD5 is a gene highly expressed in the brain encoding for a methyltransferase whose activity on lysine 36 of histone H3 (H3K36) has been recently demonstrated. Setd5 loss-of-function (LoF), which has been associated with intellectual disability and autistic spectrum disorders, leads to a reduction of H3K36me3, an epigenetic change that has been previously correlated with the aging process.
The aim of this study is to address the potential role of setd5 LoF in premature aging by evaluating specific parameters in zebrafish setd5 mutants. We found that mutant zebrafish individuals display an altered expression in selected genes involved in brain aging. Furthermore, setd5 LoF causes several age-related behavioural impairments, which we assessed through specific behavioural tests. In fact, as setd5 mutant fishes grow older, we observed a decline in social interaction and a reduction of interest for social novelty, which are significantly different from the ones we recorded for wild type fishes. Additionally, when compared to wild type fishes, mutant young fishes are less responsive to different types of stimuli and show signs of premature aging when subjected to the T-maze memory test.
Future experiments are aimed at further investigating the role of setd5 inactivation in the aging process, possibly revealing a link between the causes of intellectual disability and aging.