{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:51:46Z","timestamp":1782978706423,"version":"3.54.5"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":319,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Age\u2010related macular degeneration (AMD), the leading cause of blindness in elderly populations, involves the loss of central vision due to progressive dysfunction of the retinal pigment epithelium (RPE) and subsequent loss of light\u2010sensing photoreceptors. While age is a key risk factor, not every aged individual develops AMD. Thus, the critical question is what specific cellular changes tip the balance from healthy aging to disease. To distinguish between changes associated with aging and AMD, we compared the RPE proteome in human eye bank tissue from nondiseased donors during aging (<jats:italic>n<\/jats:italic> = 50, 29\u201091 years) and in donors with AMD (<jats:italic>n<\/jats:italic> = 36) compared to age\u2010matched donors without disease (<jats:italic>n<\/jats:italic> = 28). Proteins from RPE cells were separated on two\u2010dimensional gels, analyzed for content, and identified using mass spectrometry. A total of 58 proteins displayed significantly altered content with either aging or AMD. Proteins involved in metabolism, protein turnover, stress response, and cell death were altered with both aging and AMD. However, the direction of change was predominantly opposite. With aging, we detected an overall decrease in metabolism and reductions in stress\u2010associated proteins, proteases, and chaperones. With AMD, we observed upregulation of metabolic proteins involved in glycolysis, TCA, and fatty acid metabolism, with a concurrent decline in oxidative phosphorylation, suggesting a reprogramming of energy utilization. Additionally, we detected upregulation of proteins involved in the stress response and protein turnover. Predicted upstream regulators also showed divergent results, with inhibition of inflammation and immune response with aging and activation of these processes with AMD. Our results support the idea that AMD is not simply advanced aging but rather the culmination of perturbed protein homeostasis, defective bioenergetics, and increased oxidative stress within the aging RPE, exacerbated by environmental factors and the genetic background of an individual.<\/jats:p>","DOI":"10.1155\/2022\/6009787","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T21:05:43Z","timestamp":1668632743000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dissecting Regulators of Aging and Age\u2010Related Macular Degeneration in the Retinal Pigment Epithelium"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0539-0621","authenticated-orcid":false,"given":"Pabalu P.","family":"Karunadharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Kapphahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madilyn R.","family":"Stahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2200-266X","authenticated-orcid":false,"given":"Timothy W.","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2561-7464","authenticated-orcid":false,"given":"Deborah A.","family":"Ferrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(13)70145-1"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30489-7"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.13834"},{"key":"e_1_2_11_4_2","unstructured":"Sources for Macular Degeneration: Facts & Figures August 2022 http:\/\/www.brightfocus.org\/sources-macular-degeneration-facts-figures."},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0342"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(01)01218-1"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0976"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1352"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5429"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/proteomes6020022"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-0991-2"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac026117i"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1615-9861(200209)2:9<1156::AID-PROT1156>3.0.CO;2-4"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac025747h"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac0341261"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1106"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2008.01.010"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr901109w"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)68581-9"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2016.04.010"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2006.12.006"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-1204"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3459"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.590576"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-268904"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2015.09.002"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2009.06.002"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-017-3711-0"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03422-9"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S142685"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20597-z"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092560"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00058"},{"key":"e_1_2_11_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-17121-0_106"},{"key":"e_1_2_11_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.453"},{"key":"e_1_2_11_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.05.015"},{"key":"e_1_2_11_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.05.012"},{"key":"e_1_2_11_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M900523-MCP200"},{"key":"e_1_2_11_40_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0190-15.2015"},{"key":"e_1_2_11_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31707-4"},{"key":"e_1_2_11_42_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1327"},{"key":"e_1_2_11_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101201"},{"key":"e_1_2_11_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.093"},{"key":"e_1_2_11_45_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28899"},{"key":"e_1_2_11_46_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-14633"},{"key":"e_1_2_11_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602131103"},{"key":"e_1_2_11_48_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01284"},{"key":"e_1_2_11_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101355200"},{"key":"e_1_2_11_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407445200"},{"key":"e_1_2_11_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-015-1916-3"},{"key":"e_1_2_11_52_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2310"},{"key":"e_1_2_11_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12938-021-00917-0"},{"key":"e_1_2_11_54_2","doi-asserted-by":"publisher","DOI":"10.2741\/2068"},{"key":"e_1_2_11_55_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5174957"},{"key":"e_1_2_11_56_2","first-page":"595","article-title":"T cell ageing: effects of age on development, survival & function","volume":"138","author":"Salam N.","year":"2013","journal-title":"The Indian Journal of Medical Research"},{"key":"e_1_2_11_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2013.07.003"},{"key":"e_1_2_11_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222551899"},{"key":"e_1_2_11_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-008-0112-9"},{"key":"e_1_2_11_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.100825"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/6009787.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/6009787.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2022\/6009787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T01:28:28Z","timestamp":1748914108000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2022\/6009787"}},"subtitle":[],"editor":[{"given":"Deepak","family":"Chhangani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1155\/2022\/6009787"],"URL":"https:\/\/doi.org\/10.1155\/2022\/6009787","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2022-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"6009787"}}