{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:28:04Z","timestamp":1790724484911,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2011,8,22]],"date-time":"2011-08-22T00:00:00Z","timestamp":1313971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Reactive oxygen species (ROS) are wieldy accepted as one of the main factors of the aging process. These highly reactive compounds modify nucleic acids, proteins and lipids and affect the functionality of mitochondria in the first case and ultimately of the cell. Any agent or genetic modification that affects ROS production and detoxification can be expected to influence longevity. On the other hand, genetic manipulations leading to increased longevity can be expected to involve cellular changes that affect ROS metabolism. The 66-kDa isoform of the growth factor adaptor Shc (p66Shc) has been recognized as a relevant factor to the oxygen radical theory of aging. The most recent data indicate that p66Shc protein regulates life span in mammals and its phosphorylation on serine 36 is important for the initiation of cell death upon oxidative stress. Moreover, there is strong evidence that apart from aging, p66Shc may be implicated in many oxidative stress-associated pathologies, such as diabetes, mitochondrial and neurodegenerative disorders and tumorigenesis. This article summarizes recent knowledge about the role of p66Shc in aging and senescence and how this protein can influence ROS production and detoxification, focusing on studies performed on skin and skin fibroblasts.<\/jats:p>","DOI":"10.3390\/ijms12085373","type":"journal-article","created":{"date-parts":[[2011,8,24]],"date-time":"2011-08-24T07:43:32Z","timestamp":1314171812000},"page":"5373-5389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["p66Shc Aging Protein in Control of Fibroblasts Cell Fate"],"prefix":"10.3390","volume":"12","author":[{"given":"Jan M.","family":"Suski","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw 02-093, Poland"},{"name":"Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI) and LTTA Center, University of Ferrara, Ferrara 9-44121, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Karkucinska-Wieckowska","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Children\u2019s Memorial Health Institute, Warsaw 04-730, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Lebiedzinska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw 02-093, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI) and LTTA Center, University of Ferrara, Ferrara 9-44121, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Szczepanowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw 02-093, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyorgy","family":"Szabadkai","sequence":"additional","affiliation":[{"name":"University College London, Department of Cell and Developmental Biology, Consortium for Mitochondrial Research, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Duszynski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw 02-093, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Pronicki","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Children\u2019s Memorial Health Institute, Warsaw 04-730, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pinton","sequence":"additional","affiliation":[{"name":"Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI) and LTTA Center, University of Ferrara, Ferrara 9-44121, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz R.","family":"Wieckowski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nencki Institute of Experimental Biology, Warsaw 02-093, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2011,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/geronj\/11.3.298","article-title":"Aging: A theory based on free radical and radiation chemistry","volume":"11","author":"Harman","year":"1956","journal-title":"J. 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