{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T21:42:39Z","timestamp":1777326159222,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073951"],"award-info":[{"award-number":["82073951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["171036"],"award-info":[{"award-number":["171036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fok Ying Tung Education Foundation","award":["82073951"],"award-info":[{"award-number":["82073951"]}]},{"name":"Fok Ying Tung Education Foundation","award":["171036"],"award-info":[{"award-number":["171036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>27-Hydroxymangiferolic acid (27-HMA) is a naturally occurring compound in mango fruits that exhibits diverse biological functions. Here, we show that 27-HMA activates the transcriptional activity of farnesoid X receptor (FXR), a nuclear receptor transcription factor, extending the lifespan and healthspan in Caenorhabditis elegans (C. elegans). Meanwhile, the longevity-promoting effect of 27-HMA was attenuated in the mutants of nhr-8 and daf-12, the FXR homologs, indicating that the longevity effects of 27-HMA in C. elegans may depend on nuclear hormone receptors (NHRs). Further analysis revealed potential associations between the longevity effects of 27-HMA and the insulin\/insulin-like growth factor-1 signaling (IIS)\/TORC1 pathway. Moreover, 27-HMA increased the toxin resistance of nematodes and activated the expression of detoxification genes, which rely on NHRs. Finally, 27-HMA improved the age-related neurodegeneration in Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD) C. elegans models. Taken together, our findings suggest that 27-HMA is a novel FXR agonist and may prolong lifespan and healthspan via activating NHRs.<\/jats:p>","DOI":"10.3390\/molecules30051010","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:22:31Z","timestamp":1740140551000},"page":"1010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["27-Hydroxymangiferolic Acid Extends Lifespan and Improves Neurodegeneration in Caenorhabditis elegans by Activating Nuclear Receptors"],"prefix":"10.3390","volume":"30","author":[{"given":"Xiaoyan","family":"Gao","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Agriculture and Medicine, Hebei Open University, Shijiazhuang 050080, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minglv","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0704-2943","authenticated-orcid":false,"given":"Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0184-5641","authenticated-orcid":false,"given":"Shengjie","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1474-9728.2004.00125.x","article-title":"Gene expression profile of long-lived Ames dwarf mice and Little mice","volume":"3","author":"Yagi","year":"2004","journal-title":"Aging Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature08619","article-title":"Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila","volume":"462","author":"Grandison","year":"2009","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Antebi, A. 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