Ageing, Drosophila melanogaster and Epigenetics

Halim, Mardani Abdul; Tan, Florence Hui Ping; Azlan, Azali; Rasyid, Ian Ilham; Rosli, Nurlina; Shamsuddin, Shaharum; Azzam, Ghows

doi:10.21315/mjms2020.27.3.2

Cited by 9 publications

(2 citation statements)

References 88 publications

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“…Additionally, the model organism should enable researchers to interconnect multiple layers of genetic alterations with phenotypic changes to determine the role of these genes in fundamental biochemical processes [ 17–19 ]. Among animal models, Drosophila and mice are the most chosen model organisms for histone modification studies because of their well-studied genetic frameworks and the conserved molecular pathways that are relevant to human diseases [ 20 , 21 ]. However, there are challenges that impede a broader inspection of the histone modifications using these animal models.…”

Section: Introductionmentioning

confidence: 99%

Arabidopsis thaliana: a powerful model organism to explore histone modifications and their upstream regulations

Wang

et al. 2023

Epigenetics

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Histones are subjected to extensive covalent modifications that affect inter-nucleosomal interactions as well as alter chromatin structure and DNA accessibility. Through switching the corresponding histone modifications, the level of transcription and diverse downstream biological processes can be regulated. Although animal systems are widely used in studying histone modifications, the signalling processes that occur outside the nucleus prior to histone modifications have not been well understood due to the limitations including non viable mutants, partial lethality, and infertility of survivors. Here, we review the benefits of using Arabidopsis thaliana as the model organism to study histone modifications and their upstream regulations. Similarities among histones and key histone modifiers such as the Polycomb group (PcG) and Trithorax group (TrxG) in Drosophila, Human, and Arabidopsis are examined. Furthermore, prolonged cold-induced vernalization system has been well-studied and revealed the relationship between the controllable environment input (duration of vernalization), its chromatin modifications of FLOWERING LOCUS C ( FLC ), following gene expression, and the corresponding phenotypes. Such evidence suggests that research on Arabidopsis can bring insights into incomplete signalling pathways outside of the histone box, which can be achieved through viable reverse genetic screenings based on the phenotypes instead of direct monitoring of histone modifications among individual mutants. The potential upstream regulators in Arabidopsis can provide cues or directions for animal research based on the similarities between them.

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Section: Introductionmentioning

confidence: 99%

Arabidopsis thaliana: a powerful model organism to explore histone modifications and their upstream regulations

Wang

et al. 2023

Epigenetics

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“…The aging process is a physiological event commonly associated with neuronal loss, motor disabilities, metabolism alterations, cellular senescence, augmented reactive oxygen species (ROS) levels, lipid peroxidation, fragility, and increased susceptibility to diseases [1][2][3]. Harman and his theory of free radicals (1950) described the basal mechanism of aging as a result of the accumulation of ROS, produced as by-products of cellular metabolism and decreasing lifespan [4,5].…”

Section: Introductionmentioning

confidence: 99%

Increased Iron Levels and Oxidative Stress Mediate Age-Related Impairments in Male and Female Drosophila melanogaster

Gomes

Santos

Anjos

et al. 2023

Oxidative Medicine and Cellular Longevity

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Aging is characterized by a functional decline in the physiological functions and organic systems, causing frailty, illness, and death. Ferroptosis is an iron- (Fe-) dependent regulated cell death, which has been implicated in the pathogenesis of several disorders, such as cardiovascular and neurological diseases. The present study investigated behavioral and oxidative stress parameters over the aging of Drosophila melanogaster that, together with augmented Fe levels, indicate the occurrence of ferroptosis. Our work demonstrated that older flies (30-day-old) of both sexes presented impaired locomotion and balance when compared with younger flies (5-day-old). Older flies also produced higher reactive oxygen species (ROS) levels, decreased glutathione levels (GSH), and increased lipid peroxidation. In parallel, Fe levels were augmented in the fly’s hemolymph. The GSH depletion with diethyl maleate potentiated the behavioral damage associated with age. Our data demonstrated biochemical effects that characterize the occurrence of ferroptosis over the age of D. melanogaster and reports the involvement of GSH in the age-associated damages, which could be in part attributed to the augmented levels of Fe.

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Behavioural Effects and RNA-seq Analysis of Aβ42-Mediated Toxicity in a Drosophila Alzheimer’s Disease Model

et al. 2023

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Alzheimer's disease (AD) is the most common neurological ailment worldwide. Its process comprises the unique aggregation of extracellular senile plaques composed of amyloid-beta (Aβ) in the brain. Aβ42 is the most neurotoxic and aggressive of the Aβ42 isomers released in the brain. Despite much research on AD, the complete pathophysiology of this disease remains unknown. Technical and ethical constraints place limits on experiments utilizing human subjects. Thus, animal models were used to replicate human diseases as a result. The Drosophila melanogaster is an excellent model for studying both physiological and behavioural aspects of human neurodegenerative illnesses. Here, the negative effects of Aβ42-expression on a Drosophila AD model were investigated through three behavioural assays followed by RNA-seq. The RNA-seq data was veri ed using qPCR. AD Drosophila expressing human Aβ42 exhibited degenerated eye structures, shortened lifespan and declined mobility function compared to the wild-type Control. RNAseq revealed 1496 genes that were differentially expressed from the Aβ42-expressing samples against the Control. Among the pathways that were identi ed from the differentially expressed genes include carbon metabolism, oxidative phosphorylation, antimicrobial peptides and longevity regulating pathways. While AD is a complicated neurological condition whose aetiology is in uenced by a number of factors, it is hoped that the current data will be su cient to give a general picture of how Aβ42 in uences the disease pathology. The discovery of molecular connections from the current Drosophila AD model offers fresh perspectives on the usage of this Drosophila which could aid in the discovery of new anti-AD medications. HighlightsAβ42 expression in the Drosophila eye resulted in severe rough eye phenotype.Drosophila melanogaster expressing Aβ42 exhibited shortened lifespan.Aβ42-expressing Drosophila melanogaster had impaired climbing abilities.From the RNA-seq analysis, AD samples showed 1496 DEGs compared to Control.

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Ageing, Drosophila melanogaster and Epigenetics

Cited by 9 publications

References 88 publications

Arabidopsis thaliana: a powerful model organism to explore histone modifications and their upstream regulations

Arabidopsis thaliana: a powerful model organism to explore histone modifications and their upstream regulations

Increased Iron Levels and Oxidative Stress Mediate Age-Related Impairments in Male and Female Drosophila melanogaster

Behavioural Effects and RNA-seq Analysis of Aβ42-Mediated Toxicity in a Drosophila Alzheimer’s Disease Model

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