Study

Curated
Gabrawy et al., 2019
Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster
[10.1093/gerona/glz152][FBrf0244035]

Description

Virgin males of three DGRP lines were kept on control food or with 1 mM of the ACE inhibitor Lisinopril, and their life span and climbing speed, endurance and strength at 1, 3 and 5 weeks were measured. Lisinopril extended life span in all three lines, with genotype-specific effects on performance.

Comments from curator

Only the authors' per-line sensitivity indices (Table 1) are available for this study.

The authors studied virgin males of three DGRP lines (DGRP_073, DGRP_229 and DGRP_304, chosen for their different life spans in Durham et al., 2014), kept on control food or on food containing 1 mM of the ACE inhibitor Lisinopril. They measured:
- Climbing speed: time for a single fly to climb 9 cm in an inverted 25-mL serological pipette (plotted in cm/s).
- Endurance: distance climbed in the same pipette in 15 s, or time to reach 27 cm (plotted in cm).
- Strength: time for a fly, chilled 60 s at -20 °C and placed dorsal side down on double-sided tape, to escape (maximum 3 min; plotted as the inverse of the time, in 1/s).
These were measured on 30 flies per line, treatment, age (1, 3 and 5 weeks) and assay, with new flies at each age (540 flies per line).
- Life span: one population cage of 250-270 males per line and treatment, deaths scored every other day.
- Feeding rate (capillary feeder assay), protein aggregation in the indirect flight muscles at 1 and 5 weeks, and the transcriptome (RNA-seq) of DGRP_073 and DGRP_229 at 1 and 5 weeks.
The Ance RNAi experiments used Gal4/UAS stocks, not DGRP lines.

Per-line values of these traits are only shown as plots in Figures 1, 2 and 4 and Supplementary Figures 2 and 3 of the paper (PMC version). Following DGRPool rules, they were not digitised. The single supplementary file (glz152_suppl_supplementary_materials.docx) contains:
- Table S1: the ANCOVA/ANOVA tables for climbing speed, endurance and strength.
- Tables S2-S5: RNA-seq differentially expressed genes and gene ontology clusters.
- Supplementary Figures 1-5.
None of them has per-line values. No repository is cited for the phenotype data, and no accession was found for the RNA-seq data.

Summary dataset: the 9 values per line of Table 1 (Sensitivity to Effects of Aging in DGRP Genotypes), copied as published, males (sex M), 3 lines. Each value is Falconer's sensitivity index of climbing speed (AgeSensSpeed), endurance (AgeSensEndur) or strength (AgeSensStrength) to age, between weeks 1 and 3 (_w1_3), 3 and 5 (_w3_5) or 1 and 5 (_w1_5). The paper defines it as the mean of the line at the earlier age minus its mean at the later age, divided by the average change across all lines. A higher value means a steeper age-related decline. Since the average is taken over these three lines, the index is relative to them: each index sums to 3 over the three lines (checked, within rounding).

Caveats:
- The paper does not say whether the indices were computed on control flies, Lisinopril-treated flies or both.
- The text states that climbing speed and endurance of DGRP_073 were much more sensitive to age than those of the other lines, but in Table 1 the week 1-5 endurance index is highest for DGRP_229 (1.447, vs 0.967 for DGRP_073).
- In Figure 1, the control climbing speed of DGRP_304 does not decrease between weeks 1 and 3, whereas its week 1-3 index is 0.857.
- The Results and Discussion disagree on which line's physical performance responded to Lisinopril (DGRP_073 or DGRP_229), and the Results cite Figure 1 panels that do not match the figure legend.
These issues only affect the interpretation. The values are uploaded as published.

The same three lines were also used in Ederer et al., 2018 (Int J Mol Sci 19:3351), which measured the effects of Lisinopril on mitochondrial and metabolic parameters. That paper is not in DGRPool.

3 DGRP lines 3 genotyped

DGRP_073 DGRP_229 DGRP_304

Datasets

Dataset Phenotypes DGRP lines
Summary dataset 9 phenotypes
AgeSensEndur_w1_3 AgeSensEndur_w1_5 AgeSensEndur_w3_5 AgeSensSpeed_w1_3 AgeSensSpeed_w1_5 AgeSensSpeed_w3_5 AgeSensStrength_w1_3 AgeSensStrength_w1_5 AgeSensStrength_w3_5
3 DGRP lines
DGRP_073
DGRP_229
DGRP_304
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