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In humans, excessive dietary NaCl can cause high blood pressure, which contributes to age-related diseases, including stroke and heart disease. We used Caenorhabditis elegans to elucidate how NaCl levels influence animal aging. Most experiments on this animal are conducted in standard culture conditions: Nematode Growth Medium (NGM) agar with a lawn of E. coli. Here, we report that the supplemental NaCl in standard NGM, \u223c50\u2005mM, accelerates aging and decreases lifespan. For comparison, we prepared NGM with reduced NaCl or excess NaCl. Considering reduced NaCl as a baseline, wild-type worms on standard NGM displayed normal development and fertility but reduced lifespan and health span, indicating toxicity in old animals. The long-lived mutants daf-2, age-1, and nuo-6, cultured on standard NGM, also displayed reduced lifespan. Thus, NaCl in standard NGM accelerates aging in multiple genetic backgrounds. Wild-type worms on excess NaCl displayed delayed development and reduced fertility, and reduced lifespan and health span, indicating toxicity in both young and old animals. These results suggest that young animals are relatively resistant to NaCl toxicity, but that aging causes progressive sensitivity, such that old animals display toxicity to both standard and excess NaCl. We investigated pathways that respond to NaCl. Young animals cultured with excess NaCl activated gpdh-1, a specific response to NaCl stress. Old animals cultured with excess NaCl activated gpdh-1 and hsp-6, a reporter for the mitochondrial unfolded protein response. Thus, excess NaCl activates multiple stress response pathways in older animals.<\/jats:p>","DOI":"10.1093\/genetics\/iyaf139","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T05:15:15Z","timestamp":1755494115000},"source":"Crossref","is-referenced-by-count":2,"title":["Environmental NaCl affects <i>Caenorhabditis elegans<\/i> development and aging"],"prefix":"10.1093","volume":"231","author":[{"given":"Franziska","family":"Pohl","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["United States"]},{"name":"Department of Medicine, Washington University School of Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["United States"]},{"name":"Present Affiliation: Nutrition Innovation Center, Standard Process, Inc. , Kannapolis, NC 28081 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3770-5605","authenticated-orcid":false,"given":"Brian M","family":"Egan","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["United States"]},{"name":"Present Affiliation: School of Medicine, University of Kansas Medical Center , Kansas City, KS 66160 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9408-8901","authenticated-orcid":false,"given":"Daniel L","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew C","family":"Mosley","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micklaus A","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sydney","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Hao","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of 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