Evidence map›Paper›PMID 41534066›Full record

ArticleAging cell2026

Selection for Postponed Senescence in Drosophila melanogaster Reveals Distinct Metabolic Aging Trajectories Modifiable by the Angiotensin-Converting Enzyme Inhibitor Lisinopril.

Denise Vecchié, Robert R H Anholt, Trudy F C Mackay, Maria De Luca

Abstract read
In one paragraph

Article in Aging cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Denise VecchiéDepartment of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Robert R H AnholtInstitute for Human Genetics and Department of Genetics and Biochemistry, Clemson University, Greenwood, South Carolina, USA.
Trudy F C MackayInstitute for Human Genetics and Department of Genetics and Biochemistry, Clemson University, Greenwood, South Carolina, USA.
Maria De LucaDepartment of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.ORCID 0000-0001-6345-7508

Funding

University of Washington Nathan Shock Center of Excellence in the Basic Biology of AgingP30AG013280 · NIA · UNIVERSITY OF WASHINGTON · PI Maitreya J Dunham · 1995 to 2026
$27.1M
Sex hormones and arthritis in a long lived animal modelP30AG050886 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Jianhua Zhang · 2015 to 2026
$11.3M
Genetic Basis of Lifespan and Healthspan Extension by ACE Inhibition in DrosophilaR01AG073181 · NIA · CLEMSON UNIVERSITY · PI Robert R. H Anholt, MARIA DE LUCA · 2022 to 2026
$2.4M
Systems Genetics of Drosophila Life SpanR01AG043490 · NIA · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI ANHOLT, ROBERT R. H, CARBONE, MARY ANNA · 2013 to 2017
$1.9M
Genetic Basis of Lifespan and Healthspan Extension by ACE Inhibition in DrosophilaR56AG073181 · NIA · CLEMSON UNIVERSITY · PI ANHOLT, ROBERT R. H, DE LUCA, MARIA ANTONIETTA · 2021 to 2021
$271k
NIA NIH HHS AG043490NIA NIH HHS AG050886NIA NIH HHS AG073181NIA NIH HHS P30 AG013280NIA NIH HHS P30 AG050886NIA NIH HHS R01 AG043490NIA NIH HHS R01 AG073181NIA NIH HHS R56 AG073181
6 · The paper itself

Abstract

Aging is accompanied by profound changes in energy metabolism, yet the underlying drivers and modulators of these shifts remain incompletely understood. Here, we investigated how life-history evolution shapes metabolic aging and pharmacological responsiveness by leveraging Drosophila melanogaster lines divergently selected for reproductive timing. We measured organismal oxygen consumption rate and performed untargeted metabolomics in young and old flies of both sexes from long-lived "O" lines (selected for female late-life reproduction) and unselected "B" control lines. Males and females from the O lines maintained stable metabolic rates and largely preserved metabolite profiles with age, whereas B line flies showed age-related increases in oxygen consumption, citrate accumulation, and elevated levels of medium- and long-chain fatty acids, hallmarks of mitochondrial inefficiency and impaired lipid oxidation. Aged B flies also displayed elevated S-adenosylmethionine, reduced sarcosine, and diminished heme levels, indicating dysregulation of one-carbon metabolism and impaired heme biosynthesis. Furthermore, Vitamin B6 metabolites, pyridoxamine, pyridoxal, and 4-pyridoxate, increased with aging only in B line females. Motivated by evidence implicating the renin-angiotensin system in metabolic aging, we treated flies with the angiotensin-converting enzyme (ACE) inhibitor lisinopril. Lisinopril prevented the age-related rise in metabolic rate in B line females, aligning their metabolic phenotype with that of O line flies. This suggests that ACE inhibition may buffer against age-associated increases in metabolic rate and contribute to enhanced metabolic stability. Our results show that selection for delayed reproduction and increased lifespan modifies age-related metabolic trajectories and modulates physiological responses to pharmacological intervention.

Indexed as

AgingAngiotensin-Converting Enzyme InhibitorsDrosophila melanogasterLisinoprilAnimalsEnergy MetabolismFemaleMaleOxygen ConsumptionAngiotensin-Converting Enzyme InhibitorsLisinoprilenergy metabolismlongevitymetabolomicspostponed reproductive senescencerenin‐angiotensin system blockade

Identifiers

PMID41534066
PMCPMC12803505

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.