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Research Article | Open Access

Novel human milk-derived probiotics delays senescence and improves antioxidant capacity in Caenorhabditis elegans by affecting the insulin signaling pathway

Yu Zhanga,b,c,1Bin Liub,c,1Yuying Yuana,b,cXueping Yuana,b,c,dShujuan Dia,b,cJunying Zhaob,cWeicang Qiaob,cXianping Lib,cLu Liub,cZonghan Zhoua,b,cJuncai Houa,e( )Lijun Chena,b,c ( )
Key Laboratory of Dairy Science, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin 150030, China
National Engineering Research Center of Dairy Health for Maternal and Child, Beijing Sanyuan Foods Co., Ltd., Beijing 100163, China
Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co., Ltd., Beijing 100163, China
School of Biological Engineering, Dalian Polytechnic University, Dalian 116034, China
College of Food Science and Engineering, Guiyang University, Guiyang 550005, China

1 These authors contributed equally to this article.

Peer review under responsibility of Beijing Academy of Food Sciences.

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Highlights

• Human milk-derived probiotics extended lifespan in Caenorhabditis elegans.

• Reduced lipofuscin and ROS accumulation observed with novel probiotics.

• Probiotics enhanced antioxidant enzyme via insulin signaling and DAF-16 regulation.

• Probiotics promote DAF-16 nuclear localization and do not daf-16 mutant strain lifespan.

Abstract

Probiotics have received considerable attention owing to their potential benefits in maintaining intestinal health, modulating immune function, and antioxidant activity. The antioxidant capacity of recently isolated and screened probiotics have not been characterized. Therefore, the present study used Caenorhabditis elegans as a model to investigate the effects of three novel probiotics (Limosilactobacillus reuteri B1-10, Lactobacillus paragasseri B1-26, and Lacticaseibacillus rhamnosus B2-1) and their probiotic complexes, isolated from breast milk, on the ability to delay aging and antioxidant capacity. Probiotics significantly prolonged the lifespan of nematodes by reducing lipofuscin accumulation, and their average lifespan was prolonged by 19.40% (B1-10), 7.72% (B1-26), 19.72% (B2-1) and 20.30% (complex probiotic), respectively. The probiotics reduce nematode fecundity and retard their growth and development, possibly due to dietary restriction. Additionally, the probiotics reduced the accumulation of reactive oxygen species and malondialdehyde content, the reductions were 9.7%–44.5% and 18.69%–46.99%, respectively, and increased the activity of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione, the increases were 26.22% to 41.72%, 30.33% to 83.20% and 77.13% to 171.85%, respectively. The complex probiotic was the most effective in improving the C. elegans resistance to hydrogen peroxide stressors. Furthermore, the probiotics acts on the insulin/insulin-like pathway to regulate the expression of daf-16, which in turn upregulates the expression of sod-3, ctl-1, sod-1, down-regulated the expression of age-1, and promoted the nuclear localization of DAF-16::GFP nematodes to prolong the lifespan and antioxidant capacity of C. elegans. These results provide a new basis and research direction for further analyses of the role of probiotics in maintaining the health, improving stress resistance, and prolonging the lifespan of the host. They also provide potential insights into the development of functional food to facilitate anti-aging management in humans.

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Food Science and Human Wellness
Article number: 9250547

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Cite this article:
Zhang Y, Liu B, Yuan Y, et al. Novel human milk-derived probiotics delays senescence and improves antioxidant capacity in Caenorhabditis elegans by affecting the insulin signaling pathway. Food Science and Human Wellness, 2026, 15(6): 9250547. https://doi.org/10.26599/FSHW.2025.9250547

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Received: 02 December 2024
Revised: 23 December 2024
Accepted: 13 February 2025
Published: 14 July 2026
© 2026 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).