{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:21:45Z","timestamp":1791206505130,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,6,9]],"date-time":"2015-06-09T00:00:00Z","timestamp":1433808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIGMS-NIH","award":["P20GM103629"],"award-info":[{"award-number":["P20GM103629"]}]},{"name":"ATS\/Scleroderma Foundation","award":["552114G1"],"award-info":[{"award-number":["552114G1"]}]},{"name":"Wetmore Foundation","award":["551165G1"],"award-info":[{"award-number":["551165G1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Aging constitutes a significant risk factor for fibrosis, and idiopathic pulmonary fibrosis (\n                    <jats:styled-content style=\"fixed-case\">IPF<\/jats:styled-content>\n                    ) is characteristically associated with advancing age. We propose that age\u2010dependent defects in the quality of protein and cellular organelle catabolism may be causally related to pulmonary fibrosis. Our research found that autophagy diminished with corresponding elevated levels of oxidized proteins and lipofuscin in response to lung injury in old mice and middle\u2010aged mice compared to younger animals. More importantly, older mice expose to lung injury are characterized by deficient autophagic response and reduced selective targeting of mitochondria for autophagy (mitophagy). Fibroblast to myofibroblast differentiation (\n                    <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content>\n                    ) is an important feature of pulmonary fibrosis in which the profibrotic cytokine\n                    <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                    \u03b21 plays a pivotal role. Promotion of autophagy is necessary and sufficient to maintain normal lung fibroblasts\u2019 fate. On the contrary,\n                    <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content>\n                    mediated by\n                    <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                    \u03b21 is characterized by reduced autophagy flux, altered mitophagy, and defects in mitochondrial function. In accord with these findings,\n                    <jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>\n                    1 expression appeared to be reduced in fibrotic lung tissue from bleomycin and a\n                    <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                    \u03b21\u2010adenoviral model of lung fibrosis.\n                    <jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>\n                    1 expression is also reduced in the aging murine lung and biopsies from\n                    <jats:styled-content style=\"fixed-case\">IPF<\/jats:styled-content>\n                    patients compared to controls. Furthermore, deficient\n                    <jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>\n                    1 promotes a profibrotic environment. Collectively, this study indicates that an age\u2010related decline in autophagy and mitophagy responses to lung injury may contribute to the promotion and\/or perpetuation of pulmonary fibrosis. We propose that promotion of autophagy and mitochondrial quality control may offer an intervention against age\u2010related fibrotic diseases.\n                  <\/jats:p>","DOI":"10.1111\/acel.12357","type":"journal-article","created":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T23:51:34Z","timestamp":1433980294000},"page":"774-783","source":"Crossref","is-referenced-by-count":164,"title":["Deregulation of selective autophagy during aging and pulmonary fibrosis: the role of\n                    <scp>TGF<\/scp>\n                    \u03b21"],"prefix":"10.1111","volume":"14","author":[{"given":"Meredith L.","family":"Sosulski","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Pulmonary Diseases, Critical Care and Environmental Medicine Tulane University Health Sciences Center New Orleans LA 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Gongora","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Pulmonary Diseases, Critical Care and Environmental Medicine Tulane University Health Sciences Center New Orleans LA 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svitlana","family":"Danchuk","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Pulmonary Diseases, Critical Care and Environmental Medicine Tulane University Health Sciences Center New Orleans LA 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmin","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Pulmonary Diseases, Critical Care and Environmental Medicine Tulane University Health Sciences Center New Orleans LA 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayong","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Pulmonary Diseases, Critical Care and Environmental Medicine Tulane University Health Sciences Center New Orleans LA 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia G.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Pulmonary Diseases, Critical Care and Environmental Medicine Tulane University Health Sciences Center New Orleans LA 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-014-1132-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-012-9491-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00213.2012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2011.595714"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-014-9626-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.4.10766"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64125"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2002.02869.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74942"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.152363"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9728.2004.00129.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.10.582"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003316"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.7.10.6665"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068352"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-62"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2010.03.004"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2012"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100527"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00217.2014"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-3701-4-2"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008182"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00330"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-6-16"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.08.003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2009.01672.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.4.12244"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(03)00095-0"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr1009355"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094616"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(02)00091-2"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041394"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059348"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3300"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.09.002"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2014.02.015"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2006.07.003"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11866"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e318234c132"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.4236\/abb.2014.51004"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.12.001"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1194-6"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-13-0661"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00151.2001"}],"container-title":["Aging 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