Gadd45 expression correlates with age dependent neurodegeneration in Drosophila melanogaster

Abstract

The neurodegeneration is one of the features of aging and age-related disorders. Yet, only several antiaging interventions are known to affect the processes of neurodegeneration. Here we show that overexpression of the pro-longevity gene D-GADD45 in Drosophila neurons leads to a postponed manifestation of histological and ultrastructural features of age-dependent neurodegeneration, such as decrease in the packing density of neurons, increasing the degree of neuron cytoplasmic vacuolization, and morphological defects of mitochondrial cristae. Thus, the previously observed (Plyusnina, Biogerontology 12: 211-226, 2011) life extending effect of D-GADD45 overexpression in the nervous system is associated with delayed neurodegeneration.

Lifespan and Stress Resistance in Drosophila with Overexpressed DNA Repair Genes

“…Indeed, the loss of heterochromatin and subsequent accumulation of DNA damage in the Drosophila brain have been shown to promote neurodegeneration 52 . Moreover, other experiments involving overexpression of Ku70 and D-GADD45 confirm that DNA repair genes are important for maintaining the normal functions of neurons and the prevention of age-related neurodegeneration 51 53 .…”

“…Evidence suggests that that the nervous system plays a critical role in longevity and the aging process 51 . The results of the current study lend support for this view by demonstrating that lifespan in Drosophila can be increased by overexpression of DNA repair genes in the adult nervous system alone (under the control of the neurospecific driver Elav-GS ).…”

LncRNA mediated regulation of aging pathways in Drosophila melanogaster during dietary restriction

“…Especially in FoxO signaling pathway, three ( Gadd45, Pepck, Egfr ) of seven differentially expressed coding genes were found to be up-regulated at the 42 day of DR when compared to fully fed flies as the targets of novel lncRNA ( XLOC_000246, XLOC_076307, XLOC_000043, XLOC_221562 and XLOC_001163 ). Gadd45 and Egfr had been reported to be involved in Drosophila senescence [ 27 , 28 ]. Adipose tissue is a major source of energy, which declines in old age [ 23 , 29 ].…”

Drosophila nervous system as a target of aging and anti-aging interventions

“…At the initial 30 day of age Gompertz curve is close to the linear dependence with the R slope, at later 60 day of age the curve decrease exponentially. Our study of normal expression of D-GADD45 gene during aging showed that D-GADD45 brain expression is vanishing at critical point of 30 day old (Bgatova et al, 2015). …”

“…The brain from old flies demonstrates the ultrastructural neurodegenerative changes such as reduction in the number of synapses, defects in mitochondria, and increase in neuronal apoptosis (Haddadi et al, 2014). However, anti-aging interventions may postpone the neurodegeneration (Bgatova et al, 2015). …”