舍曲林可促进秀丽隐杆线虫的健康和长寿。

IF 3.1 3区 医学 Q3 GERIATRICS & GERONTOLOGY Gerontology Pub Date : 2024-01-01 Epub Date: 2024-01-16 DOI:10.1159/000536227
Yu Liang, Yiming Zhou, Can Zhou, Xinqi Cai, Li Liu, Fang Wei, Guolin Li
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引用次数: 0

摘要

简介:虽然有几种抗抑郁药被认为是潜在的老年保护剂,但舍曲林对健康寿命的影响和机制仍有待阐明。在此,我们探讨了舍曲林在秀丽隐杆线虫(C. elegans)寿命和健康寿命中的作用:方法:首先在热胁迫条件下对野生型N2蠕虫筛选舍曲林的最佳作用浓度。然后,我们考察了舍曲林对寿命、繁殖、脂褐素积累、移动性和抗应激能力的影响。最后,研究了5-HT信号转导和衰老相关基因的表达以探索其潜在机制,并在ser-7 RNAi株、daf-2、daf-16和aak-2突变体中进行了寿命测定:结果:舍曲林延长了秀丽隐杆线虫的寿命,同时延长了健康寿命,这表现在增加了活动能力、降低了生育力和脂褐质积累,以及增强了对不同非生物胁迫的抵抗力。从机理上讲,ser-7通过调控胰岛素和AMPK通路协调了舍曲林诱导的长寿,在ser-7 RNAi株、daf-2、daf-16和aak-2突变体中,舍曲林诱导的线虫寿命延长被取消:结论:舍曲林通过ser-7-胰岛素/AMPK通路促进秀丽隐杆线虫的健康和长寿。
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Sertraline Promotes Health and Longevity in Caenorhabditis elegans.

Introduction: While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans.

Methods: The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants.

Results: Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants.

Conclusion: Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.

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来源期刊
Gerontology
Gerontology 医学-老年医学
CiteScore
6.00
自引率
0.00%
发文量
94
审稿时长
6-12 weeks
期刊介绍: In view of the ever-increasing fraction of elderly people, understanding the mechanisms of aging and age-related diseases has become a matter of urgent necessity. ''Gerontology'', the oldest journal in the field, responds to this need by drawing topical contributions from multiple disciplines to support the fundamental goals of extending active life and enhancing its quality. The range of papers is classified into four sections. In the Clinical Section, the aetiology, pathogenesis, prevention and treatment of agerelated diseases are discussed from a gerontological rather than a geriatric viewpoint. The Experimental Section contains up-to-date contributions from basic gerontological research. Papers dealing with behavioural development and related topics are placed in the Behavioural Science Section. Basic aspects of regeneration in different experimental biological systems as well as in the context of medical applications are dealt with in a special section that also contains information on technological advances for the elderly. Providing a primary source of high-quality papers covering all aspects of aging in humans and animals, ''Gerontology'' serves as an ideal information tool for all readers interested in the topic of aging from a broad perspective.
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