Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice.
Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice.
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DOI：
10.1016/j.exger.2016.12.003
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发表时间：
2017-03
影响因子：
3.9
通讯作者：
Nichenametla SN
中科院分区：
文献类型：
--
作者：
Mattocks DA;Mentch SJ;Shneyder J;Ables GP;Sun D;Richie JP Jr;Locasale JW;Nichenametla SN
尽管有充分证据证明蛋氨酸限制（MR）可延长寿命，但其潜在机制仍不清楚。由于甲硫氨酸可以改变S-腺苷甲硫氨酸（SAM）和S-腺苷高半胱氨酸（SAH），DNA甲基转移酶-1（DNMT 1）的底物和产物，我们假设MR饮食改变DNA甲基化。用不同水平的蛋氨酸（0.12%-MR，0.84%-CD）喂养幼年（8周龄）和成年（1岁）雄性C57 BL/6 J小鼠12周。在不同组织中评估DNA甲基化的功能指标，包括整体甲基化（GM）、基因特异性甲基化（GSM）和LINE-1甲基化;以及影响DNA甲基化、SAH、SAM和DNMT 1的生化因素。MR改变DNA甲基化取决于干预的年龄。MR对幼龄动物肝脏GM无影响，但使成年动物GM比CD增加27%（P<0.01）。CD组大鼠肝脏GM含量比青年组低17%（P<0.05），MR组大鼠肝脏GM含量无显著性差异。MR诱导的肝GM增加与成人SAH水平降低38%相关（P<0.001），SAH和GM水平呈负相关（r2=0.33，p<0.001）。肝脏中DNMT蛋白水平未观察到变化。在脂肪组织中，MR导致成人GM下降6%（p<0.05），SAH相应增加2倍（p<0.05），DNMT 1减少2倍（p<0.01）。MR引起肝脏和脂肪GSM的增加和减少。LINE-1中未观察到变化。总之，这些研究结果提供了证据，MR饮食对成人肝脏DNA低甲基化的保护作用，显然是由SAH介导的。这些发现还表明，改变的DNA甲基化可能在MR饮食带来的益处中发挥作用。
Despite well-documented evidence for lifespan extension by methionine restriction (MR), underlying mechanisms remain unknown. As methionine can alter S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the substrate and product of DNA methyltransferase-1 (DNMT1), we hypothesized that MR diet alters DNA methylation. Young (8-week-old) and adult (1-year-old) male C57BL/6J mice were fed diets with different levels of methionine (0.12%-MR, 0.84%-CD) for 12 weeks. Functional indicators of DNA methylation, including global methylation (GM), gene-specific methylation (GSM) and LINE-1 methylation; and biochemical factors affecting DNA methylation, SAH, SAM, and DNMT1 were assessed in different tissues. MR altered DNA methylation depending on the age of intervention. While MR had no effect on hepatic GM in young animals, it increased GM by 27% over CD in adults (P<0.01). In comparison with young animals, hepatic GM levels were 17% lower in CD adults (P<0.05), but not different in MR adults. The MR-induced increase in hepatic GM was associated with a 38% decrease in SAH levels in adults (P<0.001), with SAH and GM levels being negatively correlated (r2=0.33, p<0.001). No changes were observed in DNMT protein levels in liver. In adipose tissue, MR caused a 6% decline in GM in adults (p<0.05), a corresponding 2-fold increase in SAH (p<0.05), and a 2-fold decrease in DNMT1 (p<0.01). MR caused both increases and decreases in GSM of liver and adipose. No changes were observed in LINE-1. Together, these findings provide evidence for protective effects of MR diet on hepatic DNA hypomethylation in adults, apparently mediated by SAH. These findings also indicate that altered DNA methylation might be playing a role in benefits conferred by MR diet.
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DOI：
10.1186/2046-2395-3-10
发表时间：
2014
期刊：
Longevity & healthspan
影响因子：
--
作者：
Brown-Borg HM;Rakoczy S;Wonderlich JA;Armstrong V;Rojanathammanee L
通讯作者：
Rojanathammanee L
影响因子：
7.8
作者：
Jones MJ;Goodman SJ;Kobor MS
通讯作者：
Kobor MS
影响因子：
9.8
作者：
MUDD, SH;POOLE, JR
通讯作者：
POOLE, JR
影响因子：
7.7
作者：
Hasek BE;Boudreau A;Shin J;Feng D;Hulver M;Van NT;Laque A;Stewart LK;Stone KP;Wanders D;Ghosh S;Pessin JE;Gettys TW
通讯作者：
Gettys TW
影响因子：
12.3
作者：
Horvath S
通讯作者：
Horvath S