# Short lifespan under dietary cholesterol depletion is associated with gut dysfunction in Drosophila melanogaster females

**Authors:** Brooke Zanco, Christen K. Mirth, Carla M. Sgrò, Matthew D. W. Piper

PMC · DOI: 10.1038/s41514-026-00341-5 · 2026-02-19

## TL;DR

Reducing dietary cholesterol shortens lifespan in fruit flies by causing gut problems, suggesting gut health is important for longevity.

## Contribution

The study shows that gut dysfunction is a key factor in lifespan reduction under cholesterol-limited diets in female fruit flies.

## Key findings

- Low-cholesterol diets increased intestinal permeability in Drosophila females.
- Cholesterol limitation was associated with reduced lifespan and gut dysfunction.
- Not all flies lost gut barrier function before death, suggesting variability in aging processes.

## Abstract

Dietary restriction may extend lifespan by improving late-life gut health. Because micronutrients mediate the effects of macronutrient ratios on longevity, we examined how cholesterol limitation affects gut health in female Drosophila melanogaster. Low-cholesterol diets increased intestinal permeability and reduced lifespan, however, not all flies lost barrier function before dying. This indicates gut dysfunction is either a marker of ageing, or contributes to death, but predominantly during dietary cholesterol limitation.

## Linked entities

- **Chemicals:** cholesterol (PubChem CID 5997)
- **Species:** Drosophila melanogaster (taxon 7227)

## Full-text entities

- **Diseases:** gut dysfunction (MESH:C535334), death (MESH:D003643)
- **Chemicals:** cholesterol (MESH:D002784)
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13031265/full.md

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Source: https://tomesphere.com/paper/PMC13031265