Knockout of Hsp70 Genes Modulates Age-Related Transcriptomic Changes in Leg Muscles and Reduces the Locomotion Speed and Lifespan of Drosophila melanogasterстатьяИсследовательская статья
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Аннотация:This study investigated the effect of knockout of six Hsp70 genes (orthologues of the mammaliangenes Hspa1a, Hspa1b, Hspa2, and Hspa8) on age-related changes in gene expression in the legs of Drosophilamelanogaster, which contain predominantly skeletal muscle bundles. For this, the leg transcriptomic profilewas examined in males of the w1118 control strain and the Hsp70– strain on the 7th, 23rd and 47th days of life.In w1118 flies, an age-related decrease in the locomotion (climbing) speed (a marker of functional state andendurance) was accompanied by a pronounced change in the transcriptomic profile of the leg skeletal muscles, which is conservative in nature. In Hsp70– flies, the median lifespan was shorter and the locomotionspeed was significantly lower compared to the control; at the same time, complex changes in the age-relateddynamics of the skeletal muscle transcriptome were observed. Mass spectrometry-based quantitative proteomics showed that 47-day-old Hsp70– flies, compared with w1118 flies, demonstrated multidirectionalchanges in the contents of key enzymes of glucose metabolism and fat oxidation (glycolysis, pentose phosphate pathway, Krebs cycle, beta-oxidation, and oxidative phosphorylation). Such dysregulation may beassociated with a compensatory increase in the expression of other genes encoding chaperones (small Hsp,Hsp40, 60, and 70), which regulate specific sets of target proteins. Taken together, our data show that knockout of six Hsp70 genes slightly reduced the median lifespan of flies, but significantly reduced the locomotionspeed, which may be associated with complex changes in the transcriptome of the leg skeletal muscles andwith multidirectional changes in the contents of key enzymes of energy metabolism.