{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:10:34Z","timestamp":1791994234248,"version":"4.4.0"},"reference-count":55,"publisher":"SAGE Publications","issue":"17","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Sirtuins, a family of NAD\n                      <jats:sup>+<\/jats:sup>\n                      -dependent deacetylases, are recognized as nondispensable regulators of aging processes. Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase that maintains mitochondrial bioenergetics, an essential prerequisite for healthy aging. In this study, using\n                      <jats:italic toggle=\"yes\">Sirt3<\/jats:italic>\n                      knockout (\n                      <jats:italic toggle=\"yes\">\n                        Sirt3\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      ) mice, we sought to establish whether\n                      <jats:italic toggle=\"yes\">Sirt3<\/jats:italic>\n                      deficiency affected life span, an endpoint that has never been tested formally in mammals, and uncover the mechanisms involved in organ damage associated with aging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">\n                        Sirt3\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice experienced a shorter life span than wild-type mice and severe cardiac damage, characterized by hypertrophy and fibrosis, as they aged. No alterations were found in organs other than the heart.\n                      <jats:italic toggle=\"yes\">Sirt3<\/jats:italic>\n                      deficiency altered cardiac mitochondrial bioenergetics and caused hyperacetylation of optic atrophy 1 (OPA1), a SIRT3 target. These changes were associated with aberrant alignment of trans-mitochondrial cristae in cardiomyocytes, and cardiac dysfunction. Gene transfer of deacetylated\n                      <jats:italic toggle=\"yes\">Opa1<\/jats:italic>\n                      restored cristae alignment in\n                      <jats:italic toggle=\"yes\">\n                        Sirt3\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice, ameliorated cardiac reserve capacity, and protected the heart against hypertrophy and fibrosis. The translational relevance of these findings is in the data showing that\n                      <jats:italic toggle=\"yes\">SIRT3<\/jats:italic>\n                      silencing in human-induced pluripotent stem cell-derived cardiomyocytes led to mitochondrial dysfunction and altered contractile phenotype, both rescued by\n                      <jats:italic toggle=\"yes\">Opa1<\/jats:italic>\n                      gene transfer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>Our findings indicate that future approaches to heart failure could include SIRT3 as a plausible therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      SIRT3 has a major role in regulating mammalian life span.\n                      <jats:italic toggle=\"yes\">Sirt3<\/jats:italic>\n                      deficiency leads to cardiac abnormalities, due to defective trans-mitochondrial cristae alignment and impaired mitochondrial bioenergetics. Correcting cardiac OPA1 hyperacetylation through gene transfer diminished heart failure in\n                      <jats:italic toggle=\"yes\">\n                        Sirt3\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice during aging.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      31, 1255\u20131271.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2018.7703","type":"journal-article","created":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T09:28:27Z","timestamp":1562232507000},"page":"1255-1271","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":112,"title":["<i>Sirt3<\/i>\n                    Deficiency Shortens Life Span and Impairs Cardiac Mitochondrial Function Rescued by\n                    <i>Opa1<\/i>\n                    Gene Transfer"],"prefix":"10.1177","volume":"31","author":[{"given":"Ariela","family":"Benigni","sequence":"first","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cassis","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Conti","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Perico","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Corna","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Cerullo","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Zentilin","sequence":"additional","affiliation":[{"name":"Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlamaria","family":"Zoja","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Perna","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Lionetti","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy."},{"name":"UOS Anesthesia and Intensive Care, Fondazione Toscana \u201cG. Monasterio\u201d, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Giacca","sequence":"additional","affiliation":[{"name":"Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy."},{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piera","family":"Trionfini","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Tomasoni","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Remuzzi","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy."},{"name":"L. Sacco\u2019 Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,10,25]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.009775"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803790105"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.2.481"},{"key":"e_1_3_5_5_2","first-page":"484","article-title":"Myocardial response to infarction in the rat. Morphometric measurement of infarct size and myocyte cellular hypertrophy","volume":"118","author":"Anversa P","year":"1985","unstructured":"Anversa P, , Beghi C, , Kikkawa Y, , and Olivetti G. Myocardial response to infarction in the rat. Morphometric measurement of infarct size and myocyte cellular hypertrophy. 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