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This study was designed to identify a dietary method of extending lifespan, promoting renoprotection, and preventing muscle weakness in aged mice, with a focus on the importance of the balance between dietary essential (\n                    <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>\n                    s) and nonessential amino acids (\n                    <jats:styled-content style=\"fixed-case\">NEAA<\/jats:styled-content>\n                    s) on the dietary restriction (\n                    <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\n                    )\u2010induced antiaging effect. Groups of aged mice were fed ad\u00a0libitum, a simple\n                    <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\n                    , or a\n                    <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\n                    with recovering\n                    <jats:styled-content style=\"fixed-case\">NEAA<\/jats:styled-content>\n                    s or\n                    <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>\n                    s. Simple\n                    <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\n                    significantly extended lifespan and ameliorated age\u2010related kidney injury; however, the beneficial effects of\n                    <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\n                    were canceled by recovering dietary\n                    <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>\n                    but not\n                    <jats:styled-content style=\"fixed-case\">NEAA<\/jats:styled-content>\n                    . Simple\n                    <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\n                    prevented the age\u2010dependent decrease in slow\u2010twitch muscle fiber function but reduced absolute fast\u2010twitch muscle fiber function.\n                    <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\n                    \u2010induced fast\u2010twitch muscle fiber dysfunction was improved by recovering either dietary\n                    <jats:styled-content style=\"fixed-case\">NEAA<\/jats:styled-content>\n                    s or\n                    <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>\n                    s. In the ad\u00a0libitum\u2010fed and the\n                    <jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>\n                    plus\n                    <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>\n                    groups, the renal content of methionine, an\n                    <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>\n                    , was significantly higher, accompanied by lower renal production of hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S), an endogenous antioxidant. Finally, removal of methionine from the dietary\n                    <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>\n                    supplement diminished the adverse effects of dietary\n                    <jats:styled-content style=\"fixed-case\">EAA<\/jats:styled-content>\n                    on lifespan and kidney injury in the diet\u2010restricted aged mice, which were accompanied by a recovery in H\n                    <jats:sub>2<\/jats:sub>\n                    S production capacity and lower oxidative stress. These data imply that a dietary approach could combat kidney aging and prolong lifespan, while preventing muscle weakness, and suggest that renal methionine metabolism and the trans\u2010sulfuration pathway could be therapeutic targets for preventing kidney aging and subsequently promoting healthy aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.12796","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T01:41:22Z","timestamp":1529977282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Role of dietary amino acid balance in diet restriction\u2010mediated lifespan extension, renoprotection, and muscle weakness in aged mice"],"prefix":"10.1111","volume":"17","author":[{"given":"Shohei","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Yamahara","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science Otsu Shiga Japan"},{"name":"Department of Medicine IV Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kume","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Koya","sequence":"additional","affiliation":[{"name":"Department of Diabetology and Endocrinology Kanazawa Medical University Kahoku\u2010Gun Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Yasuda\u2010Yamahara","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science Otsu Shiga Japan"},{"name":"Department of Medicine IV Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihisa","family":"Osawa","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Chin\u2010Kanasaki","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Adachi","sequence":"additional","affiliation":[{"name":"Frontier Research Labs Institute for Innovation Ajinomoto Co., Inc. 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