{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:31:46Z","timestamp":1758709906863},"reference-count":40,"publisher":"Portland Press Ltd.","issue":"5","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,10,1]]},"abstract":"<jats:p>Autophagy, a highly conserved proteolytic mechanism of quality control, is essential for the maintenance of metabolic and cellular homoeostasis and for an efficient cellular response to stress. Autophagy declines with aging and is believed to contribute to different aspects of the aging phenotype. The nutrient-sensing pathways PKA (protein kinase A), Sch9 and TOR (target of rapamycin), involved in the regulation of yeast lifespan, also converge on a common targeted process: autophagy. The molecular mechanisms underlying the regulation of autophagy and aging by these signalling pathways in yeast, with special attention to the TOR pathway, are discussed in the present paper. The question of whether or not autophagy could contribute to yeast cell death occurring during CLS (chronological lifespan) is discussed in the light of our findings obtained after autophagy activation promoted by proteotoxic stress. Autophagy progressively increases in cells expressing the aggregation-prone protein \u03b1-synuclein and seems to participate in the early cell death and shortening of CLS under these conditions, highlighting that autophagic activity should be maintained below physiological levels to exert its promising anti-aging effects.<\/jats:p>","DOI":"10.1042\/bst0391466","type":"journal-article","created":{"date-parts":[[2012,5,3]],"date-time":"2012-05-03T12:32:44Z","timestamp":1336048364000},"page":"1466-1470","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Yeast chronological lifespan and proteotoxic stress: is autophagy good or bad?"],"prefix":"10.1042","volume":"39","author":[{"given":"Bel\u00e9m","family":"Sampaio-Marques","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, and ICVS\/3B's \u2013 PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Carolina","family":"Felgueiras","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, and ICVS\/3B's \u2013 PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Alexandra","family":"Silva","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, and ICVS\/3B's \u2013 PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Fernando","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, and ICVS\/3B's \u2013 PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Paula","family":"Ludovico","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, and ICVS\/3B's \u2013 PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Portugal"}]}],"member":"288","published-online":{"date-parts":[[2011,9,21]]},"reference":[{"key":"2021111900565271800_B1","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1126\/science.290.5497.1717","article-title":"Autophagy as a regulated pathway of cellular degradation","volume":"290","author":"Klionsky","year":"2000","journal-title":"Science"},{"key":"2021111900565271800_B2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ceb.2005.06.007","article-title":"Autophagosemes: biogenesis from scratch?","volume":"17","author":"Reggiori","year":"2005","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021111900565271800_B3","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.tig.2008.10.002","article-title":"Autophagy and aging: keeping that old broom working","volume":"24","author":"Cuervo","year":"2008","journal-title":"Trends Genet."},{"key":"2021111900565271800_B4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2217\/14796708.3.3.309","article-title":"Autophagy in neuroprotection and neurodegeneration: a question of balance","volume":"3","author":"Cherra","year":"2008","journal-title":"Future Neurol."},{"key":"2021111900565271800_B5","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/ncb0910-842","article-title":"Can autophagy promote longevity?","volume":"12","author":"Madeo","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"2021111900565271800_B6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1242\/jcs.064576","article-title":"The regulation of autophagy: unanswered questions","volume":"124","author":"Chen","year":"2011","journal-title":"J. Cell Sci."},{"key":"2021111900565271800_B7","doi-asserted-by":"crossref","first-page":"357","DOI":"10.18632\/aging.100040","article-title":"Growth and aging: a common molecular mechanism","volume":"1","author":"Blagosklonny","year":"2009","journal-title":"Aging"},{"key":"2021111900565271800_B8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10522-004-7382-y","article-title":"Testing the \u2018garbage\u2019 accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy","volume":"6","author":"Stroikin","year":"2005","journal-title":"Biogerontology"},{"key":"2021111900565271800_B9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.4161\/auto.1.3.2017","article-title":"Autophagy and aging: the importance of maintaining \u2018clean\u2019 cells","volume":"1","author":"Cuervo","year":"2005","journal-title":"Autophagy"},{"key":"2021111900565271800_B10","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.mad.2007.04.003","article-title":"Low auxotrophy-complementing amino acid concentrations reduce yeast chronological life span","volume":"128","author":"Gomes","year":"2007","journal-title":"Mech. Ageing Dev."},{"key":"2021111900565271800_B11","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1126\/science.1172539","article-title":"Extending healthy life span: from yeast to humans","volume":"328","author":"Fontana","year":"2010","journal-title":"Science"},{"key":"2021111900565271800_B12","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1126\/science.1115535","article-title":"Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients","volume":"310","author":"Kaeberlein","year":"2005","journal-title":"Science"},{"key":"2021111900565271800_B13","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.cub.2004.03.059","article-title":"Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway","volume":"14","author":"Kapahi","year":"2004","journal-title":"Curr. Biol."},{"key":"2021111900565271800_B14","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nature08221","article-title":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","volume":"460","author":"Harrison","year":"2009","journal-title":"Nature"},{"key":"2021111900565271800_B15","doi-asserted-by":"crossref","first-page":"847","DOI":"10.4161\/auto.8824","article-title":"Autophagy is required for extension of yeast chronological life span by rapamycin","volume":"5","author":"Alvers","year":"2009","journal-title":"Autophagy"},{"key":"2021111900565271800_B16","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1371\/journal.pgen.0040024","article-title":"A role for autophagy in the extension of lifespan by dietary restriction in C. elegans","volume":"4","author":"Hansen","year":"2008","journal-title":"PLoS Genet."},{"key":"2021111900565271800_B17","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1474-9726.2009.00469.x","article-title":"Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae","volume":"8","author":"Alvers","year":"2009","journal-title":"Aging Cell"},{"key":"2021111900565271800_B18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","author":"He","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"2021111900565271800_B19","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1083\/jcb.147.2.435","article-title":"Formation process of autophagosome is traced with Apg8\/Aut7p in yeast","volume":"147","author":"Kirisako","year":"1999","journal-title":"J. Cell Biol."},{"key":"2021111900565271800_B20","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.1074\/jbc.275.8.5845","article-title":"The itinerary of a vesicle component, Aut7p\/Cvt5p, terminates in the yeast vacuole via the autophagy\/Cvt pathways","volume":"275","author":"Huang","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021111900565271800_B21","doi-asserted-by":"crossref","first-page":"6463","DOI":"10.1074\/jbc.M008162200","article-title":"Regulation of APG14 expression by the GATA-type transcription factor Gln3p","volume":"276","author":"Chan","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021111900565271800_B22","doi-asserted-by":"crossref","first-page":"3290","DOI":"10.1091\/mbc.e07-12-1292","article-title":"Atg8 controls phagophore expansion during autophagosome formation","volume":"19","author":"Xie","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"2021111900565271800_B23","doi-asserted-by":"crossref","first-page":"14866","DOI":"10.1073\/pnas.96.26.14866","article-title":"Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins","volume":"96","author":"Hardwick","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111900565271800_B24","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1016\/j.febslet.2007.01.096","article-title":"Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae","volume":"581","author":"Suzuki","year":"2007","journal-title":"FEBS Lett."},{"key":"2021111900565271800_B25","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1083\/jcb.150.6.1507","article-title":"Tor-mediated induction of autophagy via an Apg1 protein kinase complex","volume":"150","author":"Kamada","year":"2000","journal-title":"J. Cell Biol."},{"key":"2021111900565271800_B26","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1128\/MCB.01344-09","article-title":"Tor directly controls the Atg1 kinase complex to regulate autophagy","volume":"30","author":"Kamada","year":"2010","journal-title":"Mol. Cell Biol."},{"key":"2021111900565271800_B27","doi-asserted-by":"crossref","first-page":"616","DOI":"10.4161\/auto.5.5.8091","article-title":"Tap42-associated protein phosphatase type\u00a02A negatively regulates induction of autophagy","volume":"5","author":"Yorimitsu","year":"2009","journal-title":"Autophagy"},{"key":"2021111900565271800_B28","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1091\/mbc.e07-05-0485","article-title":"Protein kinase A and Sch9 cooperatively regulate induction of autophagy in Saccharomyces cerevisiae","volume":"18","author":"Yorimitsu","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"2021111900565271800_B29","doi-asserted-by":"crossref","first-page":"13933","DOI":"10.1073\/pnas.0501046102","article-title":"An evolutionary proteomics approach identifies substrates of the cAMP-dependent protein kinase","volume":"102","author":"Budovskaya","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111900565271800_B30","doi-asserted-by":"crossref","first-page":"17049","DOI":"10.1073\/pnas.0903316106","article-title":"The Tor and PKA signaling pathways independently target the Atg1\/Atg13 protein kinase complex to control autophagy","volume":"106","author":"Stephan","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111900565271800_B31","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1074\/jbc.273.7.3963","article-title":"Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast","volume":"273","author":"Noda","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021111900565271800_B32","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.molcel.2007.04.020","article-title":"Sch9 is a major target of TORC1 in Saccharomyces cerevisiae","volume":"26","author":"Urban","year":"2007","journal-title":"Mol. Cell"},{"key":"2021111900565271800_B33","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1091\/mbc.e10-03-0182","article-title":"The rapamycin-sensitive phosphoproteome reveals that TOR controls protein kinase A toward some but not all substrates","volume":"21","author":"Soulard","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"2021111900565271800_B34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1152\/physiol.00013.2008","article-title":"How to live long and prosper: autophagy, mitochondria, and aging","volume":"23","author":"Yen","year":"2008","journal-title":"Physiology"},{"key":"2021111900565271800_B35","doi-asserted-by":"crossref","first-page":"961","DOI":"10.18632\/aging.100110","article-title":"Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol","volume":"23","author":"Morselli","year":"2009","journal-title":"Aging"},{"key":"2021111900565271800_B36","doi-asserted-by":"crossref","first-page":"647","DOI":"10.4161\/auto.7.6.15191","article-title":"Longevity-relevant regulation of autophagy at the level of the acetylproteome","volume":"7","author":"Mari\u00f1o","year":"2011","journal-title":"Autophagy"},{"key":"2021111900565271800_B37","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cell.2005.01.029","article-title":"Calorie restriction: the SIR2 connection","volume":"120","author":"Guarente","year":"2005","journal-title":"Cell"},{"key":"2021111900565271800_B38","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1146\/annurev.cellbio.042308.113313","article-title":"\u03b1-Synuclein: membrane interactions and toxicity in Parkinson's disease","volume":"26","author":"Auluck","year":"2010","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2021111900565271800_B39","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1083\/jcb.200310014","article-title":"Chronological aging leads to apoptosis in yeast","volume":"164","author":"Herker","year":"2004","journal-title":"J. Cell Biol."},{"key":"2021111900565271800_B40","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s10495-009-0453-4","article-title":"Necrosis in yeast","volume":"15","author":"Eisenberg","year":"2010","journal-title":"Apoptosis"}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/39\/5\/1466\/551650\/bst0391466.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/39\/5\/1466\/551650\/bst0391466.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:57:41Z","timestamp":1637283461000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/39\/5\/1466\/86915\/Yeast-chronological-lifespan-and-proteotoxic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,21]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2011,9,21]]},"published-print":{"date-parts":[[2011,10,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bst0391466","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9,21]]}}}