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Therefore, there are several\nstudy models for the study of aging, from computational models to animals\nor even to cell cultures. The latter have shown high potential for aging studies as\nthey are easier to handle, cheaper, do not require the same level of ethical consideration\nrequired for animal and human studies, and present little biological\nheterogeneity when grown under the same conditions and in the same context\npopulation. For aging studies, these characteristics are a great advantage since\ncells have a considerable variety of morphologic characteristics and markers that\ncan be studied. Thus, the aim of this review is to offer an overview of the models\nused in studies of aging, with a focus on cell culture models, presenting the advantages\nand disadvantages of cell culture in the study of aging, of what information\ncan we extract of these studies and how cell studies can be compared with\nthe other models.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/2666338408666210322113713","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T10:58:29Z","timestamp":1616497109000},"page":"1-26","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cell Culture Studies: A Promising Approach to the Metabolomic Study of Human Aging"],"prefix":"10.2174","volume":"8","author":[{"given":"Ana","family":"Rocha","sequence":"first","affiliation":[{"name":"iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro,Portugal"}]},{"given":"Sandra","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro,Portugal"}]},{"given":"Alexandra","family":"Nunes","sequence":"additional","affiliation":[{"name":"iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro,Portugal"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"BSR20160177","DOI":"10.1042\/BSR20160177","volume":"37","author":"Mc Auley M.T.","year":"2017","unstructured":"Mc Auley M.T.; Guimera A.M.; Hodgson D.; Mcdonald N.; Mooney K.M.; Morgan A.E.; Proctor C.J.; Modelling the molecular mechanisms of aging. 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Methods Mol Biol 2013,1048,1-10","journal-title":"Methods Mol Biol"},{"key":"ref=50","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1152\/physrev.1993.73.3.617","volume":"73","author":"Cristofalo V.J.","year":"1993","unstructured":"Cristofalo V.J.; Pignolo R.J.; Replicative senescence of human fibroblast-like cells in culture. Physiol Rev 1993,73(3),617-638","journal-title":"Physiol Rev"},{"key":"ref=51","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.mad.2004.07.010","volume":"125","author":"Cristofalo V.J.","year":"2004","unstructured":"Cristofalo V.J.; Lorenzini A.; Allen R.G.; Torres C.; Tresini M.; Replicative senescence: a critical review. Mech Ageing Dev 2004,125(10-11),827-848","journal-title":"Mech Ageing Dev"},{"key":"ref=52","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/0531-5565(88)90032-0","volume":"23","author":"Cristofalo V.J.","year":"1988","unstructured":"Cristofalo V.J.; Cellular biomarkers of aging. 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