{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:56:37Z","timestamp":1790751397911,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Aging is closely implicated in the pathogenesis of chronic diseases, degenerative conditions, and mortality, making it a core research focus in geroscience. As direct secretory products of apoptotic cells, apoptotic bodies can directly reflect the intensity of apoptotic activity and the degree of systemic and cellular aging. Given their close correlation with senescence progression, apoptotic bodies hold great potential as reliable and sensitive biomarkers for evaluating aging status. However, apoptotic bodies as effective indicators of aging remain to be explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We characterized the lipid profile of apoptotic bodies (ApoEVs) and explored the changes in lipid species related to aging. Total lipids, multiple lipid subclasses, and fatty acid saturation within plasma apoptotic bodies were analyzed to identify aging-associated lipid alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>A comprehensive reduction in total lipids, multiple lipid subclasses, and fatty acid saturation within plasma apoptotic bodies highlights systemic lipid reprogramming in aging. Decreased total levels of Hex2Cer, LPC, LPE, TG, ChE, SM, and SPH are the features of aging. This study not only deepens the understanding of aging-related lipid dysfunction, but also offers circulating lipid biomarkers for assessing biological aging and age-related pathologies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1853081","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:05:16Z","timestamp":1790748316000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative lipidomics reveals Lipid perturbation of plasma apoptotic extracellular vesicles during physiological aging"],"prefix":"10.3389","volume":"14","author":[{"given":"Maojiao","family":"Li","sequence":"first","affiliation":[{"name":"West China School of Public Health and West China Fourth Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and Engineering Research Center of Oral Translational Medicine, Ministry of Education and National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haisen","family":"Huang","sequence":"additional","affiliation":[{"name":"Novital Biotechnology Company, Limited","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Tang","sequence":"additional","affiliation":[{"name":"West China School of Public Health and West China Fourth Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109806","DOI":"10.1016\/j.cellsig.2020.109806","article-title":"Structure-function analysis of lipid substrates and inhibitors of sphingosine kinases","volume":"76","author":"Adams","year":"2020","journal-title":"Cell Signal"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7439","DOI":"10.1038\/ncomms8439","article-title":"A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure","volume":"6","author":"Atkin-Smith","year":"2015","journal-title":"Nat. Commun."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e3000870","DOI":"10.1371\/journal.pbio.3000870","article-title":"High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: evidence from two large population cohort studies","volume":"18","author":"Beyene","year":"2020","journal-title":"PLoS Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/nature03260","article-title":"Rejuvenation of aged progenitor cells by exposure to a young systemic environment","volume":"433","author":"Conboy","year":"2005","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1111\/acel.12065","article-title":"Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity","volume":"12","author":"Conboy","year":"2013","journal-title":"Aging Cell"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v2i0.20677","article-title":"Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes","volume":"2","author":"Crescitelli","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"B7","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/brv.12798","article-title":"Uncovering the 'sphinx' of sphingosine 1-phosphate signalling: from cellular events to organ morphogenesis","volume":"97","author":"Cui","year":"2022","journal-title":"Biol. Rev. Camb Philos. Soc."},{"key":"B8","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13075-015-0617-2","article-title":"Enhanced activation of dendritic cells by autologous apoptotic microvesicles in MRL\/Lpr mice","volume":"17","author":"Dieker","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2710","DOI":"10.1002\/1878-0261.13223","article-title":"Lipidomic profiling of exosomes from colorectal cancer cells and patients reveals potential biomarkers","volume":"16","author":"Elmallah","year":"2022","journal-title":"Mol. Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/s41419-021-03883-6","article-title":"Emerging understanding of apoptosis in mediating mesenchymal stem cell therapy","volume":"12","author":"Fu","year":"2021","journal-title":"Cell Death Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"lnad013","DOI":"10.1093\/lifemedi\/lnad013","article-title":"Apoptotic vesicles: emerging concepts and research progress in physiology and therapy","volume":"2","author":"Fu","year":"2023","journal-title":"Life Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3385","DOI":"10.7150\/thno.94943","article-title":"Mesenchymal stem cell-derived apoptotic vesicles ameliorate impaired ovarian folliculogenesis in polycystic ovary syndrome and ovarian aging by targeting WNT signaling","volume":"14","author":"Fu","year":"2024","journal-title":"Theranostics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e12428","DOI":"10.1002\/jev2.12428","article-title":"Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence","volume":"13","author":"Huang","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e13048","DOI":"10.1111\/acel.13048","article-title":"The role of lipid metabolism in aging, lifespan regulation, and age-related disease","volume":"18","author":"Johnson","year":"2019","journal-title":"Aging Cell"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai8524","article-title":"The Fas\/Fap-1\/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing","volume":"10","author":"Kou","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"201","DOI":"10.2217\/imt-2017-0117","article-title":"Immune modulation by apoptotic dental pulp stem cells in vivo","volume":"10","author":"Laing","year":"2018","journal-title":"Immunotherapy"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e3001561","DOI":"10.1371\/journal.pbio.3001561","article-title":"Lipidomic risk scores are independent of polygenic risk scores and can predict incidence of diabetes and cardiovascular disease in a large population cohort","volume":"20","author":"Lauber","year":"2022","journal-title":"PLoS Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"797320","DOI":"10.3389\/fragi.2021.797320","article-title":"Implications of sphingolipids on aging and age-related diseases","volume":"2","author":"Li","year":"2021","journal-title":"Front. Aging"},{"key":"B19","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1177\/00220345211068338","article-title":"BMSC-derived ApoEVs promote craniofacial bone repair via ROS\/JNK signaling","volume":"101","author":"Li","year":"2022","journal-title":"J. Dent. Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/s41467-017-00698-y","article-title":"Application of bio-orthogonal proteome labeling to cell transplantation and heterochronic parabiosis","volume":"8","author":"Liu","year":"2017","journal-title":"Nat. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1186\/s13287-020-02014-w","article-title":"Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages","volume":"11","author":"Liu","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e70316","DOI":"10.1111\/acel.70316","article-title":"A global metabolomic and lipidomic landscape of human plasma across the lifespan","volume":"25","author":"Liu","year":"2026","journal-title":"Aging Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: an expanding universe","volume":"186","author":"Lopez-Otin","year":"2023","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2914","DOI":"10.1016\/j.xphs.2017.05.002","article-title":"Plasma lipidomics of healthy Japanese adults reveals Gender- and age-related differences","volume":"106","author":"Maekawa","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1016\/j.devcel.2021.03.034","article-title":"Lipid metabolism and lipid signals in aging and longevity","volume":"56","author":"Mutlu","year":"2021","journal-title":"Dev. Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1016\/j.neurobiolaging.2015.01.002","article-title":"Human prefrontal cortex phospholipids containing docosahexaenoic acid increase during normal adult aging, whereas those containing arachidonic acid decrease","volume":"36","author":"Norris","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.18632\/aging.206292","article-title":"Exosomes released from senescent cells and circulatory exosomes isolated from human plasma reveal aging-associated proteomic and lipid signatures","volume":"17","author":"Patel","year":"2025","journal-title":"Aging (Albany NY)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3791\/58317","article-title":"Detection and isolation of apoptotic bodies to high purity","volume":"138","author":"Phan","year":"2018","journal-title":"J. Vis. Exp."},{"key":"B29","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1146\/annurev-pharmtox-032723-110507","article-title":"Targeting efferocytosis in inflammaging","volume":"64","author":"Poon","year":"2024","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1172\/JCI76369","article-title":"Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy","volume":"125","author":"Proia","year":"2015","journal-title":"J. Clin. Invest"},{"key":"B31","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/s42003-023-05102-8","article-title":"Age-related changes in circadian regulation of the human plasma lipidome","volume":"6","author":"Rahman","year":"2023","journal-title":"Commun. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3390\/pharmaceutics15020437","article-title":"Lipid biomarkers in liquid biopsies: novel opportunities for cancer diagnosis","volume":"15","author":"Sagini","year":"2023","journal-title":"Pharmaceutics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1158\/1940-6207.capr-20-0612","article-title":"Lipidomic profiles of plasma exosomes identify candidate biomarkers for early detection of hepatocellular carcinoma in patients with cirrhosis","volume":"14","author":"Sanchez","year":"2021","journal-title":"Cancer Prev. Res. (Phila)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s11306-020-01709-8","article-title":"Plasma sphingolipids and risk of cardiovascular diseases: a large-scale lipidomic analysis","volume":"16","author":"Seah","year":"2020","journal-title":"Metabolomics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"111858","DOI":"10.1016\/j.mad.2023.111858","article-title":"Lipids and the hallmarks of ageing: from pathology to interventions","volume":"215","author":"Sharma","year":"2023","journal-title":"Mech. Ageing Dev."},{"key":"B36","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/nrm2934","article-title":"Lipidomics: coming to grips with lipid diversity","volume":"11","author":"Shevchenko","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12944-021-01456-2","article-title":"Age and sex are associated with the plasma lipidome: findings from the GOLDN study","volume":"20","author":"Slade","year":"2021","journal-title":"Lipids Health Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"102118","DOI":"10.1016\/j.jbc.2022.102118","article-title":"Regulation of the lysosome by sphingolipids: potential role in aging","volume":"298","author":"Tang","year":"2022","journal-title":"J. Biol. Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1159\/000530795","article-title":"Blood biomarkers for healthy aging","volume":"69","author":"Ubaida-Mohien","year":"2023","journal-title":"Gerontology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40035-020-00215-0","article-title":"Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with alzheimer's disease","volume":"9","author":"Xu","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e2303946","DOI":"10.1002\/advs.202303946","article-title":"Impaired efferocytosis enables apoptotic osteoblasts to escape osteoimmune surveillance during aging","volume":"10","author":"Xu","year":"2023","journal-title":"Adv. Sci. (Weinh)"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.7150\/ijms.94755","article-title":"The effect of age on the regenerative potential of adipose stem-cell-derived apoptotic extracellular vesicles in rat skin wound healing","volume":"21","author":"Yan","year":"2024","journal-title":"Int. J. Med. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e70196","DOI":"10.1002\/jev2.70196","article-title":"USP5-Laden ApoEVs and E2F1 stabilization in disc repair: unresolved questions on senescence, specificity and endosomal escape","volume":"14","author":"Yang","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"B44","doi-asserted-by":"publisher","first-page":"102294","DOI":"10.1016\/j.arr.2024.102294","article-title":"Lipids and lipid metabolism in cellular senescence: emerging targets for age-related diseases","volume":"97","author":"Zeng","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"ra81","DOI":"10.1126\/scisignal.2000610","article-title":"Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection","volume":"2","author":"Zernecke","year":"2009","journal-title":"Sci. Signal"},{"key":"B46","doi-asserted-by":"publisher","first-page":"114046","DOI":"10.1016\/j.biopha.2022.114046","article-title":"Metabolites as extracellular vesicle cargo in health, cancer, pleural effusion, and cardiovascular diseases: an emerging field of study to diagnostic and therapeutic purposes","volume":"157","author":"Zhang","year":"2023","journal-title":"Biomed. Pharmacother."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1853081\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:05:17Z","timestamp":1790748317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1853081\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":46,"alternative-id":["10.3389\/fcell.2026.1853081"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1853081","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1853081"}}