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Recent studies have shown that MR\u2010affected biomarkers, such as fibroblast growth factor 21, adiponectin, leptin, cystathionine \u03b2 synthase, and insulin\u2010like growth factor 1, can potentially alter physiology. The beneficial effects of MR could be explained in part by its ability to reduce mitochondrial oxidative stress. Studies have revealed that MR can reduce reactive oxygen species that damage cells and promote cancer progression. It has been demonstrated that either MR or the targeting of specific genes in the methionine cycle could induce cell apoptosis while decreasing proliferation in several cancer models. The complete mechanism underlying the actions of MR on the cell cycle during cancer has not been fully elucidated. Epigenetic mechanisms, such as methylation and noncoding RNAs, are also possible downstream effectors of MR; future studies should help to elucidate some of these mechanisms. Despite evidence that changes in dietary methionine can affect epigenetics, it remains unknown whether epigenetics is a mechanism in MR. This review summarizes research on MR and its involvement in metabolism, cancer, and epigenetics.<\/jats:p>","DOI":"10.1111\/nyas.13014","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T08:29:00Z","timestamp":1456475340000},"page":"68-79","source":"Crossref","is-referenced-by-count":45,"title":["Methionine restriction beyond life\u2010span extension"],"prefix":"10.1111","volume":"1363","author":[{"given":"Gene P.","family":"Ables","sequence":"first","affiliation":[{"name":"Orentreich Foundation for the Advancement of Science Cold Spring New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie R.","family":"Hens","sequence":"additional","affiliation":[{"name":"Orentreich Foundation for the Advancement of Science Cold Spring New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailendra N.","family":"Nichenametla","sequence":"additional","affiliation":[{"name":"Orentreich Foundation for the Advancement of Science Cold Spring New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1947.150.3.511"},{"key":"e_1_2_10_3_1","first-page":"155","article-title":"The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935","volume":"5","author":"McCay C.M.","year":"1989","journal-title":"Nutrition"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/31.2.149"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.02.009"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/jn\/123.2.269","article-title":"Low methionine ingestion by rats extends life span","volume":"123","author":"Orentreich N.","year":"1993","journal-title":"J. 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