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Abstract
Some effects of aging in animals are tissue-specific. In D. melanogaster neuronal overexpression of Gclc increases lifespan and improves certain physiological parameters associated with health benefits such as locomotor activity, circadian rhythmicity, and stress resistance. Our previous transcriptomic analyses of Drosophila heads, primarily composed of neuronal tissue, revealed significant changes in expression levels of genes involved in aging-related signaling pathways (Jak-STAT, MAPK, FOXO, Notch, mTOR, TGF-beta), translation, protein processing in endoplasmic reticulum, proteasomal degradation, glycolysis, oxidative phosphorylation, apoptosis, regulation of circadian rhythms, differentiation of neurons, synaptic plasticity, and transmission. Considering that various tissues age differently and age-related gene expression changes are tissue-specific, we investigated the effects of neuronal Gclc overexpression on gene expression levels in the imago thorax, which is primarily composed of muscles. A total of 58 genes were found to be differentially expressed between thoraces of control and Gclc overexpressing flies. The Gclc level demonstrated associations with expression of genes involved in the circadian rhythmicity, the genes in categories related to the muscle system process and the downregulation of genes involved in proteolysis. Most of the functional categories altered by Gclc overexpression related to metabolism including Drug metabolism, Metabolism of xenobiotics by cytochrome P450, Glutathione metabolism, Starch and sucrose metabolism, Citrate cycle (TCA cycle), One carbon pool by folate. Thus, the transcriptomic changes caused by neuron-specific Gclc overexpression in the thorax were less pronounced than in the head and affected pathways also differed from previous results. Although these pathways don't belong to the canonical longevity pathways, we suggest that they could participate in the delay of aging of Gclc overexpressing flies.
Highlights
The aging process is determined by the impairment functioning of tissues and systems of an organism
Our data demonstrate that the neuronal Glutamate-cysteine ligase catalytic subunit (Gclc) overexpression resulted in less pronounced effects on the gene expression, the key signaling pathways involved in the aging process in the thorax than in the head
The differential expression (DE) analysis revealed that only 58 genes (|LogFC|>1, p < 0.05) were differentially expressed in the thorax, while in the head, the neuronal Gclc overexpression altered the expression level of 188 genes
Summary
The aging process is determined by the impairment functioning of tissues and systems of an organism. The progressive loss of skeletal muscle function and mass, known as sarcopenia, is one of the useful conditions accompanied the aging process in human and underlied the critical mobility reducing and life quality decline (Herndon et al, 2002; Demontis et al, 2013; Larsson et al, 2019). It must be noted, that the aging-related muscle degeneration are determined by the progressive loss of motoneurons (Larsson et al, 2019). Interventions that contribute to the slowing down of aging of nervous tissue (including overexpression of pro-longevity genes) can have a positive effect on the state of muscle tissue and prevent dangerous structural and cellular changes
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