Role of dietary amino acid balance in diet restriction-mediated lifespan extension, renoprotection, and muscle weakness in aged mice.
Role of dietary amino acid balance in diet restriction-mediated lifespan extension, renoprotection, and muscle weakness in aged mice.
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DOI：
10.1111/acel.12796
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发表时间：
2018-08
期刊：
影响因子：
7.8
通讯作者：
Araki SI
中科院分区：
文献类型：
--
作者：
Yoshida S;Yamahara K;Kume S;Koya D;Yasuda-Yamahara M;Takeda N;Osawa N;Chin-Kanasaki M;Adachi Y;Nagao K;Maegawa H;Araki SI
延长健康寿命是老龄化社会的一个新问题。本研究旨在确定一种延长老年小鼠寿命、促进肾脏保护和预防肌肉无力的饮食方法，重点是膳食必需氨基酸（EAA）和非必需氨基酸（NEAA）之间的平衡对饮食限制（DR）诱导的抗衰老作用的重要性。各组老年小鼠自由采食，简单DR，或DR与恢复NEAA或EAA。单纯DR显著延长了寿命并改善了与年龄相关的肾损伤;然而，恢复饮食EAA而不是NEAA会取消DR的有益作用。单纯DR防止了慢缩肌纤维功能的年龄依赖性降低，但降低了绝对快缩肌纤维功能。恢复饮食中的NEAA或EAA可改善DR诱导的快缩肌纤维功能障碍。在自由采食组和DR + EAA组中，蛋氨酸（一种EAA）的肾脏含量显著较高，同时肾脏产生的内源性抗氧化剂硫化氢（H2S）较低。最后，从饮食EAA补充剂中去除蛋氨酸减少了饮食EAA对饮食限制的老年小鼠寿命和肾损伤的不良影响，并伴随着H2S生产能力的恢复和较低的氧化应激。这些数据表明，饮食方法可以对抗肾脏衰老并延长寿命，同时防止肌肉无力，并表明肾脏蛋氨酸代谢和转硫途径可以成为预防肾脏衰老并随后促进健康衰老的治疗靶点。
Extending healthy lifespan is an emerging issue in an aging society. 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 (EAAs) and nonessential amino acids (NEAAs) on the dietary restriction (DR)‐induced antiaging effect. Groups of aged mice were fed ad libitum, a simple DR, or a DR with recovering NEAAs or EAAs. Simple DR significantly extended lifespan and ameliorated age‐related kidney injury; however, the beneficial effects of DR were canceled by recovering dietary EAA but not NEAA. Simple DR prevented the age‐dependent decrease in slow‐twitch muscle fiber function but reduced absolute fast‐twitch muscle fiber function. DR‐induced fast‐twitch muscle fiber dysfunction was improved by recovering either dietary NEAAs or EAAs. In the ad libitum‐fed and the DR plus EAA groups, the renal content of methionine, an EAA, was significantly higher, accompanied by lower renal production of hydrogen sulfide (H2S), an endogenous antioxidant. Finally, removal of methionine from the dietary EAA supplement diminished the adverse effects of dietary EAA on lifespan and kidney injury in the diet‐restricted aged mice, which were accompanied by a recovery in H2S 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‐sulfuration pathway could be therapeutic targets for preventing kidney aging and subsequently promoting healthy aging.
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影响因子：
3.7
作者：
Miyagi Y;Higashiyama M;Gochi A;Akaike M;Ishikawa T;Miura T;Saruki N;Bando E;Kimura H;Imamura F;Moriyama M;Ikeda I;Chiba A;Oshita F;Imaizumi A;Yamamoto H;Miyano H;Horimoto K;Tochikubo O;Mitsushima T;Yamakado M;Okamoto N
通讯作者：
Okamoto N
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影响因子：
3.9
作者：
McKiernan, Susan H.;Colman, Ricki J.;Aiken, Erik;Evans, Trent D.;Beasley, T. Mark;Aiken, Judd M.;Weindruch, Richard;Anderson, Rozalyn M.
通讯作者：
Anderson, Rozalyn M.
影响因子：
4.8
作者：
Forster, MJ;Morris, P;Sohal, RS
通讯作者：
Sohal, RS
影响因子：
3.2
作者：
Haring, Bernhard;Selvin, Elizabeth;Rebholz, Casey M.
通讯作者：
Rebholz, Casey M.
影响因子：
10.5
作者：
Lin, SJ;Ford, E;Guarente, L
通讯作者：
Guarente, L