2023  1,500
2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 58(2024) N 2 p. 233-245; DOI 10.1134/S0026893324020109 Full Text

I.V. Kukushkina1,2, P.A. Makhnovskii1, V.G. Zgoda3, N.S. Kurochkina1, D.V. Popov1*

Knockout of Hsp70 Genes Modulates Age-Related Transcriptomic Changes in Leg Muscles and Reduces the Locomotion Speed and Lifespan of Drosophila melanogaster

1Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, 123007 Russia
2Moscow State University, Moscow, 119234 Russia
3Orekhovich Research Institute of Biomedical Chemistry, Moscow, 119121 Russia

Received - 2023-08-23; Revised - 2023-10-05; Accepted - 2023-10-13

This study investigated the effect of knockout of six Hsp70 genes (orthologues of the mammalian genes Hspa1a, Hspa1b, Hspa2, and Hspa8) on age-related changes in gene expression in the legs of Drosophila melanogaster, which contain predominantly skeletal muscle bundles. For this, the leg transcriptomic profile was 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 and endurance) 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 locomotion speed was significantly lower compared to the control; at the same time, complex changes in the age-related dynamics of the skeletal muscle transcriptome were observed. Mass spectrometry-based quantitative proteomics showed that 47-day-old Hsp70- flies, compared with w1118 flies, demonstrated multidirectional changes 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 be associated 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 locomotion speed, which may be associated with complex changes in the transcriptome of the leg skeletal muscles and with multidirectional changes in the contents of key enzymes of energy metabolism.

skeletal muscle, aging, heat shock proteins, transcriptome, proteome