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Retrotransposition and Ageing-associated Neuronal Function Decline
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Resumo(s)
The world population is progressively ageing. It is estimated that by 2050, almost onefifth
of the world population will be aged 65 years or more. Despite the significant increases
in life expectancy observed in the last century, health span remained unchanged. Therefore,
people live longer but in suboptimal conditions, which frequently lead to the development
of age-related diseases, like neurodegenerative diseases. Understanding the molecular and
cellular mechanisms underlying ageing and neurodegeneration is crucial and could provide
the means to delay, mitigate or even revert the deteriorating e↵ects associated with age-related
neurodegeneration. Recent studies have correlated increased expression of retrotransposable
elements (REs) with age, which is likely due to the tendency of RE silencing mechanisms to fail
with age. Furthermore, it was reported in flies that young individuals with a neurodegenerative
decline had premature expression of REs in their brain. However, it remains unclear whether
RE expression and mobilization are the cause or a consequence of the age-associated neuron
functional decline.
The aim of this dissertation is to determine if RE expression in the central nervous system
causes an age-associated neuronal function decline. To answer this, we developed a heterologous
and naïve inducible RE system that allows specific expression of a human long interspersed
nuclear element 1 (LINE-1 or L1) in Drosophila melanogaster neurons. Negative geotaxis assays
were performed in flies aged 2, 20, and 40 days after eclosion to assess the age-associated
neurofunctional decline.
Results revealed that the forced expression of L1 in neurons throughout lifespan does not
a↵ect neuronal function. However, both in vivo and in vitro experiments failed to demonstrate
retrotransposition events in the fly. These findings suggest that additional human factors are
required in L1 retrotransposition. Future studies will focus on determining retrotransposition capacity of L1 in the fly genome.
Descrição
Palavras-chave
Ageing Neurodegeneration Genomic instability Retrotransposons L1 Drosophila melanogaster