{"id":57522,"date":"2026-07-24T08:03:27","date_gmt":"2026-07-24T15:03:27","guid":{"rendered":"https:\/\/www.salk.edu\/?post_type=disclosure&#038;p=57522"},"modified":"2026-07-24T10:25:01","modified_gmt":"2026-07-24T17:25:01","slug":"could-this-enzyme-help-remove-zombie-cells-from-our-tissues","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/could-this-enzyme-help-remove-zombie-cells-from-our-tissues\/","title":{"rendered":"Could this enzyme help remove \u201czombie\u201d cells from our tissues?"},"content":{"rendered":"<ul style=\"margin-bottom: 30px;\">\n<li style=\"list-style: none; padding-left: -20px !important; margin-left: -20px !important;\"><strong>Highlights<\/strong><\/li>\n<li>Salk scientists identify two cellular programs linked to age-related dysfunction, ferroptosis and senescence, are mechanistically linked through the enzyme acid ceramidase<\/li>\n<li>The team finds that senescent \u201czombie\u201d cells are more vulnerable to regulated cell death through ferroptosis and that they can pass that sensitivity on to neighboring cells<\/li>\n<li>The observations suggest acid ceramidase could be a powerful therapeutic target for supporting healthy aging and preventing age-related diseases and disorders such as arthritis, dementia, and cancer<\/li>\n<\/ul>\n<p>LA JOLLA\u2014Our population is aging. The United Nations reports that by 2050, the number of people over the age of 85 on our planet is set to <em>triple. <\/em>But a longer life span isn\u2019t the same as a longer healthspan (the number of years we spend healthy). Salk Institute scientists are working to change that through foundational research that explores the cellular mechanisms driving age-related dysfunction.<\/p>\n<figure id=\"attachment_57525\"  class=\"wp-caption alignright\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"275\" class=\"img-responsive wp-image-57525 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-458x275.jpg\" alt=\"David Soriano-Castell (left) and Pam Maher (right) found senescent lung cells are more vulnerable to the cell death pathway ferroptosis, contributing to age-related dysfunction.\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-458x275.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-300x180.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-1024x614.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-768x461.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-18x12.jpg 18w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-147x88.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-585x351.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-553x332.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-750x450.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-767x460.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors-945x567.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors.jpg 1500w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><\/a><figcaption class=\"wp-caption-text\">David Soriano-Castell (left) and Pam Maher (right) found senescent lung cells are more vulnerable to the cell death pathway ferroptosis, contributing to age-related dysfunction.<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-authors.jpg\" target=\"_blank\" rel=\"noopener\">\u70b9\u51fb\u6b64\u5904<\/a> \u7528\u4e8e\u9ad8\u5206\u8fa8\u7387\u56fe\u50cf\u3002.<br \/>\u7248\u6743\uff1a\u8428\u514b\u7814\u7a76\u6240<\/figcaption><\/figure>\n<p>The latest efforts to understand cellular aging look at two processes prevalent in aged cells: 1) senescence, in which cells stop dividing but don\u2019t die, and 2) ferroptosis, in which cells lose their ability to regulate fats and eventually die. While studying human lung cells, the Salk team discovered that elevated levels of the enzyme <em>acid ceramidase <\/em>make senescent cells more susceptible to ferroptosis and can pass that vulnerability to neighboring cells.<\/p>\n<p>Experimental drugs that target acid ceramidase have already been developed for other therapeutic purposes, demonstrating that acid ceramidase is targetable and lighting the way to future innovation that could extend healthspans.<\/p>\n<p>The study published in <a href=\"https:\/\/www.nature.com\/articles\/s41419-026-09108-y#article-info\" target=\"_blank\" rel=\"noopener\"><em>Cell Death and Disease<\/em><\/a> on July 10, 2026.<\/p>\n<p>\u201cSenescent cells are linked to many age-related conditions, including arthritis, poor wound healing, and neurodegenerative diseases like Alzheimer\u2019s or Parkinson\u2019s,\u201d says senior and co-corresponding author\u00a0<a href=\"https:\/\/www.salk.edu\/zh\/scientist\/pamela-maher\/\" target=\"_blank\" rel=\"noopener\">Pam Maher, PhD,<\/a>\u00a0a research professor at Salk. \u201cOur findings are a big milestone in the ongoing public health effort to support healthy aging, as we now have a novel target for developing new therapeutics that could be applied to a multitude of diseases and disorders.\u201d<\/p>\n<p>&nbsp;<\/p>\n<h2 style=\"font-size: 20px;\"><strong>What are ferroptosis and senescence?<\/strong><\/h2>\n<p>Maher is the person to ask about ferroptosis\u2014she discovered the cellular pathway and named it (\u201coxytosis\u201d originally) in 2001. Ferroptosis is an iron-dependent cell death pathway in which the accumulation of lipid peroxides becomes toxic to cells. Healthy cells keep lipid peroxides at steady levels with the help of glutathione, an antioxidant that can stave off ferroptosis.<\/p>\n<p>Recent studies have reinforced links between ferroptosis and Alzheimer\u2019s and Parkinson\u2019s diseases, including another recent study from Maher\u2019s lab. In their recent <a href=\"https:\/\/www.nature.com\/articles\/s41420-026-03208-6\" target=\"_blank\" rel=\"noopener\"><em>Cell Death Discovery<\/em><\/a> paper, Maher\u2019s lab discovered that <a href=\"https:\/\/www.salk.edu\/zh\/news-release\/does-iron-accumulation-in-the-brain-contribute-to-neurodegeneration\/\" target=\"_blank\" rel=\"noopener\">chronic iron overexposure in neurons makes them less resilient over time and more vulnerable to neurodegeneration<\/a>.<\/p>\n<p>This study is one of many to link ferroptosis to neurodegeneration, as targeting the pathway has become a promising therapeutic strategy for age-related diseases, alongside another growing area of interest: <em>senescence. <\/em><\/p>\n<p>Cellular senescence is a biological process in which cells don\u2019t completely die but also aren\u2019t quite alive. Often referred to as \u201czombie\u201d cells, senescent cells are a hallmark of aging. Though sometimes they are harmless, other times they release harmful factors into surrounding tissues and can promote the development of diseases or disorders, including cancer.<\/p>\n<p>&nbsp;<\/p>\n<h2 style=\"font-size: 20px;\"><strong>Are ferroptosis and senescence connected during aging?<\/strong><\/h2>\n<p>Since ferroptosis and senescence have been independently linked to age-related dysfunction, and both have become promising therapeutic targets for age-related diseases, the Salk team wondered whether there was any overlap in the two cellular processes.<\/p>\n<p>To find an answer, the researchers cultured senescent human lung cells in the lab. Then, they induced ferroptosis in the senescent cells to find they were far more sensitive to the cell death pathway than young, healthy cells. The sensitivity began as senescent cells expressed progressively higher levels of an enzyme (a type of protein that can speed up chemical reactions inside cells<em>)<\/em> called <em>acid ceramidase<\/em>.<\/p>\n<figure id=\"attachment_57524\"  class=\"wp-caption aligncenter\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"576\" class=\"img-responsive wp-image-57524 size-large\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-1024x576.jpg\" alt=\": Healthy lung cells (left) and senescent lung cells (right). Salk Institute researchers found senescent lung cells are more vulnerable to the cell death pathway ferroptosis, contributing to age-related dysfunction.\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-1024x576.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-300x169.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-768x432.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-18x10.jpg 18w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-147x83.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-458x258.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-585x329.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-553x311.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-750x422.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-767x432.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy-945x532.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy.jpg 1500w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a><figcaption class=\"wp-caption-text\">Healthy lung cells (left) and senescent lung cells (right). Salk Institute researchers found senescent lung cells are more vulnerable to the cell death pathway ferroptosis, contributing to age-related dysfunction.<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/07\/260724-pr-maher-microscopy.jpg\" target=\"_blank\" rel=\"noopener\">\u70b9\u51fb\u6b64\u5904<\/a> \u7528\u4e8e\u9ad8\u5206\u8fa8\u7387\u56fe\u50cf\u3002.<br \/>\u7248\u6743\uff1a\u8428\u514b\u7814\u7a76\u6240<\/figcaption><\/figure>\n<p>After discovering that excessive acid ceramidase drives cell sensitivity to ferroptosis, the researchers removed the enzyme from senescent and non-senescent cells to see whether its absence would make cells more resilient to induced ferroptosis. <em>And it did.<\/em> Removal of acid ceramidase from cells protected both young and old cells from ferroptosis.<\/p>\n<p>\u201cThis is an entirely novel pathway that is independent of the mechanisms usually associated with ferroptosis-induced cell death, as it doesn\u2019t involve any changes in iron or glutathione levels but instead modulates the lipid metabolism,\u201d says first author David Soriano-Castell, PhD, a postdoctoral researcher in Maher\u2019s lab.<\/p>\n<p>The Salk team also observed something else: Vulnerable senescent cells were able to pass their vulnerability on to neighboring cells. This helps explain why only a few senescent cells can turn into more, ultimately impacting a larger tissue, as time goes on.<\/p>\n<p>\u201cWe have unraveled a new mechanistic connection between ferroptosis and senescence,\u201d explains Soriano-Castell. \u201cThis gives us a clear target that would eliminate two birds with one stone, eliminating senescent cells and keeping neighboring cells healthy for longer.\u201d<\/p>\n<p>&nbsp;<\/p>\n<h2 style=\"font-size: 20px;\"><strong>How does this advance healthy aging?<\/strong><\/h2>\n<p>Unrelated to the Salk study, scientists have already developed drugs to target acid ceramidase for the treatment of other diseases in which this enzyme also plays a role. The Salk findings bring forward a new potential use case for these drugs, and the fact that they are already in development is a great proof-of-concept that drugs can, in fact, be designed to target the enzyme.<\/p>\n<p>\u201cThis is only the beginning,\u201d says Soriano-Castell. \u201cThe next step is finding a more complete pathway and translating into animals and tissues, then clinical trials of our own, and so on. But what is important is that acid ceramidase is targetable, and other labs have already gotten that work started\u2014later on, we can hopefully build on what they learn.\u201d<\/p>\n<p>\u201cThe more we learn about ferroptosis,\u201d adds Maher, \u201cthe more possibilities there are for healthy aging innovations. This is an exciting time to be studying aging, resilience, and longevity, and I look forward to continuing to see how ferroptosis can be a useful target.\u201d<\/p>\n<p>&nbsp;<\/p>\n<h2 style=\"font-size: 20px;\"><strong>Other authors and funding<\/strong><\/h2>\n<p>Other authors include Marie Goujon, Nawab John Dar, and Antonio Currais of Salk.<\/p>\n<p>The work was supported by the National Institutes of Health (AG069206, AG095974) and Bundy Foundation.<\/p>\n<hr \/>\n<p><em>This press release was written by Isabella Davis<\/em><br \/>\nContact: <a href=\"mailto:press@salk.edu\">press@salk.edu<\/a><\/p>\n<hr \/>","protected":false},"featured_media":57527,"template":"","faculty":[410],"disease-research":[46,146],"class_list":["post-57522","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-pamela-maher","disease-research-cancer-biology","disease-research-aging-and-regenerative-medicine"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Could this enzyme help remove \u201czombie\u201d cells from our tissues? - Salk Institute<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/could-this-enzyme-help-remove-zombie-cells-from-our-tissues\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Could this enzyme help remove \u201czombie\u201d cells from our tissues? - Salk Institute\" \/>\n<meta property=\"og:description\" content=\"Highlights Salk scientists identify two cellular programs linked to age-related dysfunction, ferroptosis and senescence, are mechanistically linked through the enzyme acid ceramidase The team finds that senescent \u201czombie\u201d cells are more vulnerable to regulated cell death through ferroptosis and that they can pass that sensitivity on to neighboring cells The observations suggest acid ceramidase could be a powerful therapeutic target for supporting healthy aging and preventing age-related diseases and disorders such as arthritis, dementia, and cancer LA JOLLA\u2014Our population is aging. The United Nations reports that by 2050, the number of people over the age of 85 on our planet is set to triple. But a longer life span isn\u2019t the same as a longer healthspan (the number of years we spend healthy). 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