Age and mating status modulate combined efficacy of α-lipoic acid and climbing to mitigate high-fat diet-induced oxidative stress in Drosophila melanogaster

Jan 23, 2026Experimental gerontology

Age and mating status affect how alpha-lipoic acid and climbing together reduce high-fat diet oxidative stress in fruit flies

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Abstract

Combined treatment with α-lipoic acid and climbing exercise significantly enhanced oxidative stress resistance in Drosophila melanogaster on a high-fat diet.

High-fat diet intake is linked to increased oxidative stress and metabolic dysfunction.
The combination of α-lipoic acid (2 mM or 2.5 mM) and climbing exercise improved stress resistance and reduced peroxide levels in early- and mid-life flies.
Unmated flies showed the most pronounced benefits from the combined treatment, suggesting mating status influences adaptive responses.
While α-lipoic acid alone reduced fecundity, its combination with climbing exercise restored reproductive output, indicating a potential mitigation of resource-allocation issues.
In late-life groups, the interventions led to modest biochemical improvements without extending lifespan, reflecting age-related limitations in physiological adaptability.

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High-fat diet (HFD) intake is a potent inducer of oxidative stress, promoting metabolic dysfunction and accelerated ageing. Identifying interventions capable of mitigating this persistent redox burden is therefore essential. This study investigated the combined efficacy of α-lipoic acid (LA) supplementation and a daily climbing regimen in counteracting HFD-induced oxidative stress across different life stages and mating statuses in Drosophila melanogaster. Flies were maintained on an HFD and subjected to LA (2 mM or 2.5 mM), climbing exercise, or their combination during early, mid, or late life. Oxidative stress resistance was evaluated using hydrogen peroxide challenge assays, and peroxide accumulation was quantified via the FOX method. Combined LA and climbing treatment significantly enhanced stress resistance and reduced peroxide levels in early- and mid-life flies, outperforming either intervention alone. This benefit was most pronounced in unmated flies, indicating that physiological costs associated with mating diminish adaptive responsiveness. Notably, while LA alone reduced fecundity, its combination with climbing restored reproductive output, suggesting exercise-mediated alleviation of resource-allocation trade-offs. In late-life groups, the interventions produced only modest biochemical improvements without corresponding lifespan extension, highlighting age-related loss of physiological plasticity and the limited reversibility of cumulative oxidative damage. Overall, the findings demonstrated that integrating antioxidant supplementation with hormetic exercise elicited superior protection against HFD-induced oxidative stress, but the magnitude of benefit depended strongly on age and reproductive status. These results underscore the importance of early, multifaceted interventions to maintain redox balance and physiological resilience.

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Age and mating status modulate combined efficacy of α-lipoic acid and climbing to mitigate high-fat diet-induced oxidative stress in Drosophila melanogaster

Abstract

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