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Reproductive-Triggered Sterol Competition Exacerbates Age-Related Intestinal Barrier Damage in Drosophila Females
Guixiang Yu1, Kejin Chen1, Mingyao Yang2
1Key Laboratory of Luzhou City for Aging Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.
Aging Cell
|February 8, 2025
Summary
Reproduction accelerates aging and intestinal barrier damage, especially with sterol deficiency. Suppressing reproduction and managing cholesterol can extend female lifespan by protecting the gut.
Area of Science:
- Gerontology and Nutritional Biochemistry
- Molecular and Developmental Biology
Background:
- The trade-off between reproduction and lifespan is a conserved biological phenomenon.
- Nutritional competition driven by reproduction is hypothesized to accelerate aging, but mechanisms are unclear.
- Dietary imbalances, particularly nutrient deficiencies, can impact aging and organismal health.
Purpose of the Study:
- To investigate the mechanisms linking reproduction, nutrition, and aging, focusing on intestinal health.
- To identify specific nutrients whose deficiency exacerbates aging-related intestinal dysfunction.
- To explore the role of sterol metabolism and signaling pathways in the reproduction-aging trade-off.
Main Methods:
- Utilized female *Drosophila melanogaster* (fruit fly) as a model organism.
- Manipulated dietary nutrient composition, including sterol levels.
- Assessed intestinal barrier integrity, reproductive status, and lifespan.
- Employed pharmacological inhibitors (rapamycin, trametinib) targeting mTOR and Ras-Erk signaling pathways.
- Analyzed cholesterol levels and excreta morphology as biomarkers.
Main Results:
- Sterol deficiency, but not other nutrient deficiencies, significantly worsened age-related intestinal barrier deterioration.
- Sterile mutations ameliorated damage in sterol-deprived diets but not under other nutritional conditions.
- Pharmacological inhibition of mTOR/Ras-Erk signaling extended lifespan and improved intestinal barrier function, modulated by cholesterol levels.
- Excreta morphology changes serve as a sensitive biomarker for early intestinal dysfunction.
Conclusions:
- Reproductive-induced sterol competition impairs the intestinal barrier, a key factor limiting female lifespan on nutrient-imbalanced diets.
- Cholesterol metabolism plays a critical role in the interplay between reproduction, diet, and aging.
- This study elucidates the link between reproductive resource allocation and somatic maintenance, impacting our understanding of diet and aging.
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