{"doi":"10.1101/2022.02.24.481867","title":"Conserved neuropeptidergic regulation of intestinal integrity in invertebrate models of aging","abstract":"Abstract Age-related decline in intestinal barrier function impacts survival across species, but the underlying cell intrinsic and extrinsic factors remain unclear. Here, we demonstrate a role for neuropeptides in regulating aging-associated increases in intestinal leakiness. Adult-specific knockdown of insulin-like peptides daf-28 or ins-7 in C. elegans neurons or dilp3 in D. melanogaster neurons improves intestinal integrity and lifespan of these animals, respectively. Neuropeptide knockdowns activate intestinal DAF-16/FOXO transcription factor that likely increases expression of epithelial barrier components. Furthermore, age-associated changes in neuronal DAF-28 peptide secretion mirrors C. elegans reproductive span and overexpression of this peptide suppresses the improved intestinal health in long-lived germline-less animals. Collectively, we show that intestinal integrity is subject to neuronal regulation, and this neuropeptidergic axis may be modulated by the animal’s germline.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300954,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":631879,"name":"Bhagyashree Kaduskar","orcid":"0000-0002-8506-1309","position":1,"is_corresponding":false},{"id":827793,"name":"Kirthi C. Reddy","orcid":"0000-0002-4328-9161","position":2,"is_corresponding":false},{"id":431837,"name":"Caroline Kumsta","orcid":"0000-0003-3839-4888","position":3,"is_corresponding":false},{"id":245851,"name":"Ethan Bier","orcid":"0000-0002-2892-3005","position":4,"is_corresponding":false},{"id":431836,"name":"Malene Hansen","orcid":"0000-0002-6828-8640","position":5,"is_corresponding":false},{"id":559094,"name":"Sreekanth H. Chalasani","orcid":"0000-0003-2522-8338","position":6,"is_corresponding":false},{"id":354244,"name":"Anupama Singh","orcid":"0000-0002-9311-073X","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T00:31:57.812980Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}