Selection for Postponed Senescence in Drosophila melanogaster Reveals Distinct Metabolic Aging Trajectories Modifiable by the Angiotensin-Converting Enzyme Inhibitor Lisinopril.
Level 5 - mechanism / opinion, no new human data
Bench and animal research using Drosophila melanogaster.
PubMed 41534066 · doi:10.1111/acel.70375
What was done
Researchers compared whole-organism oxygen consumption rates and untargeted metabolomic profiles in young and old male and female Drosophila melanogaster. They contrasted long-lived "O" lines (selected for postponed senescence via late-life female reproduction) against standard unselected control "B" lines. They also tested whether pharmacological treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril altered age-associated metabolic shifts.
What was found
The abstract reports directional metabolic changes without exact numerical values, percentages, or effect sizes. Long-lived O line flies maintained stable metabolic rates and preserved metabolite profiles with age. In contrast, aging B line control flies demonstrated increased oxygen consumption, citrate accumulation, elevated medium- and long-chain fatty acids, increased S-adenosylmethionine, reduced sarcosine, and decreased heme levels. In B line females specifically, vitamin B6 metabolites (pyridoxamine, pyridoxal, and 4-pyridoxate) increased with age. Treatment with lisinopril prevented the age-associated rise in metabolic rate in B line females, shifting their metabolic phenotype toward that of the long-lived O line.
Why it matters
This study links genetic selection for delayed senescence to the preservation of mitochondrial and one-carbon metabolic pathways in an insect model. It also indicates that pharmacological targeting of the renin-angiotensin-aldosterone system with an established clinical drug can modulate metabolic aging trajectories.
Limits
The study was conducted entirely in Drosophila melanogaster; findings regarding invertebrate metabolism and ACE homologues cannot be directly extrapolated to human physiology without mammalian and clinical validation. Sample sizes, drug dosages, and exact quantitative effect sizes were not reported in the abstract.
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