{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:51:39Z","timestamp":1789170699132,"version":"build-2803163510"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Improving healthy life expectancy by targeting aging-related pathological changes has been the spotlight of geroscience. Scorpions have been used in traditional medicine in Asia and Africa for a long time. We have isolated heat-resistant peptides from scorpion venom of Buthusmartensii Karsch (SVHRP) and found that SVHRP can attenuate microglia activation and protect <jats:italic>Caenorhabditis elegans<\/jats:italic> (<jats:italic>C. elegans<\/jats:italic>) against \u03b2-amyloid toxicity. Based on the amino acid sequence of these peptides, scorpion venom heat\u2013resistant synthesized peptide (SVHRSP) was prepared using polypeptide synthesis technology. In the present study, we used <jats:italic>C. elegans<\/jats:italic> as a model organism to assess the longevity-related effects and underlying molecular mechanisms of SVHRSP <jats:italic>in vivo<\/jats:italic>. The results showed that SVHRSP could prolong the lifespan of worms and significantly improve the age-related physiological functions of worms. SVHRSP increases the survival rate of larvae under oxidative and heat stress and decreases the level of reactive oxygen species and fat accumulation <jats:italic>in vivo<\/jats:italic>. Using gene-specific mutation of <jats:italic>C. elegans<\/jats:italic>, we found that SVHRSP-mediated prolongation of life depends on Daf-2, Daf-16, Skn-1, and Hsf-1 genes. These results indicate that the antiaging mechanism of SVHRSP in nematodes might be mediated by the insulin\/insulin-like growth factor-1 signaling pathway. Meanwhile, SVHRSP could also up-regulate the expression of stress-inducing genes Hsp-16.2, Sod-3, Gei-7, and Ctl-1 associated with aging. In general, our study may have important implications for SVHRSP to promote healthy aging and provide strategies for research and development of drugs to treat age-related diseases.<\/jats:p>","DOI":"10.3389\/fphar.2022.919269","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T07:14:58Z","timestamp":1657782898000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Scorpion Venom Heat\u2013Resistant Synthesized Peptide Increases Stress Resistance and Extends the Lifespan of Caenorhabditis elegans via the Insulin\/IGF-1-Like Signal Pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Ying-Zi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Yu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Li","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao-Ran","family":"Sui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Xiao","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kundu","family":"Supratik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.5483\/bmbrep.2016.49.2.261","article-title":"The Role of insulin\/IGF-1 Signaling in the Longevity of Model Invertebrates, C. elegans and D. melanogaster","volume":"49","author":"Altintas","year":"2016","journal-title":"BMB Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1101\/gad.1107803","article-title":"SKN-1 Links C. elegans Mesendodermal Specification to a Conserved Oxidative Stress Response","volume":"17","author":"An","year":"2003","journal-title":"Genes Dev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e02077","DOI":"10.7554\/eLife.02077","article-title":"Age- and Diet-Associated Metabolome Remodeling Characterizes the Aging Process Driven by Damage Accumulation","volume":"3","author":"Avanesov","year":"2014","journal-title":"Elife"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1001\/jama.2018.9562","article-title":"Aging as a Biological Target for Prevention and Therapy","volume":"320","author":"Barzilai","year":"2018","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.4137\/JEN.S39887","article-title":"Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity","volume":"10","author":"Beckhauser","year":"2016","journal-title":"J. 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