{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:30:14Z","timestamp":1793295014416,"version":"4.5.0"},"reference-count":80,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T00:00:00Z","timestamp":1427155200000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/na","name":"Molecular and Cellular Medicine,Blizard Institute","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cellular senescence can modulate various pathologies and is associated with irreparable DNA double-strand breaks (IrrDSBs). Extracellular senescence metabolomes (ESMs) were generated from fibroblasts rendered senescent by proliferative exhaustion (PEsen) or 20 Gy of \u03b3 rays (IrrDSBsen) and compared with those of young proliferating cells, confluent cells, quiescent cells, and cells exposed to repairable levels of DNA damage to identify novel noninvasive markers of senescent cells. ESMs of PEsen and IrrDSBsen overlapped and showed increased levels of citrate, molecules involved in oxidative stress, a sterol, monohydroxylipids, tryptophan metabolism, phospholipid, and nucleotide catabolism, as well as reduced levels of dipeptides containing branched chain amino acids. The ESM overlaps with the aging and disease body fluid metabolomes, supporting their utility in the noninvasive detection of human senescent cells in vivo and by implication the detection of a variety of human pathologies. Intracellular metabolites of senescent cells showed a relative increase in glycolysis, gluconeogenesis, the pentose-phosphate pathway, and, consistent with this, pyruvate dehydrogenase kinase transcripts. In contrast, tricarboxylic acid cycle enzyme transcript levels were unchanged and their metabolites were depleted. These results are surprising because glycolysis antagonizes senescence entry but are consistent with established senescent cells entering a state of low oxidative stress.<\/jats:p>","DOI":"10.1021\/pr501221g","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T08:23:37Z","timestamp":1424247817000},"page":"1854-1871","source":"Crossref","is-referenced-by-count":233,"title":["Senescent Human Fibroblasts\nShow Increased Glycolysis\nand Redox Homeostasis with Extracellular Metabolomes That Overlap\nwith Those of Irreparable DNA Damage, Aging, and Disease"],"prefix":"10.1021","volume":"14","author":[{"given":"Emma L.","family":"James","sequence":"first","affiliation":[{"name":"Queen Mary University of London , , Turner Street , ,","place":["London, United Kingdom, E1 2AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan D.","family":"Michalek","sequence":"additional","affiliation":[{"name":"Metabolon, Inc. , 617 Davis Drive, Suite 400 , , ,","place":["Durham, North Carolina, United States, 27713"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayani N.","family":"Pitiyage","sequence":"additional","affiliation":[{"name":"Queen Mary University of London , , Turner Street , ,","place":["London, United Kingdom, E1 2AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"de Castro","sequence":"additional","affiliation":[{"name":"Queen Mary University of London , , Turner Street , ,","place":["London, United Kingdom, E1 2AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie S.","family":"Vignola","sequence":"additional","affiliation":[{"name":"Metabolon, Inc. , 617 Davis Drive, Suite 400 , , ,","place":["Durham, North Carolina, United States, 27713"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Jones","sequence":"additional","affiliation":[{"name":"Metabolon, Inc. , 617 Davis Drive, Suite 400 , , ,","place":["Durham, North Carolina, United States, 27713"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Mohney","sequence":"additional","affiliation":[{"name":"Metabolon, Inc. , 617 Davis Drive, Suite 400 , , ,","place":["Durham, North Carolina, United States, 27713"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward D.","family":"Karoly","sequence":"additional","affiliation":[{"name":"Metabolon, Inc. , 617 Davis Drive, Suite 400 , , ,","place":["Durham, North Carolina, United States, 27713"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen S.","family":"Prime","sequence":"additional","affiliation":[{"name":"Queen Mary University of London , , Turner Street , ,","place":["London, United Kingdom, E1 2AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Kenneth","family":"Parkinson","sequence":"additional","affiliation":[{"name":"Queen Mary University of London , , Turner Street , ,","place":["London, United Kingdom, E1 2AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2015,2,18]]},"reference":[{"issue":"20","key":"2026090223330674100_cit1a","doi-asserted-by":"crossref","first-page":"9363","DOI":"10.1073\/pnas.92.20.9363","article-title":"A biomarker that identifies\nsenescent human cells in culture and in aging skin in vivo","volume":"92","author":"Dimri","year":"1995","journal-title":"Proc. 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