Late-life dietary folate restriction reduces biosynthetic processes without compromising healthspan in mice.
Late-life dietary folate restriction reduces biosynthetic processes without compromising healthspan in mice.
复制标题
晚年膳食叶酸限制会减少生物合成过程，而不影响小鼠的健康寿命。
DOI：
10.1101/2024.01.12.575290
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Kaeberlein,Matt
中科院分区：
文献类型：
--
作者：
Blank,HeidiM;Hammer,StaciE;Boatright,Laurel;Roberts,Courtney;Heyden,KatarinaE;Nagarajan,Aravindh;Tsuchiya,Mitsuhiro;Brun,Marcel;Johnson,CharlesD;Stover,PatrickJ;Sitcheran,Raquel;Kennedy,BrianK;Adams,LGarry;Kaeberlein,Matt
叶酸是细胞生长所需的维生素，以叶酸的形式存在于强化食品中，以防止先天性畸形。低叶酸水平对终身健康的影响知之甚少。我们发现，限制叶酸水平与叶酸拮抗剂甲氨蝶呤增加酵母和蠕虫的寿命。然后，我们限制老年小鼠的叶酸摄入量，并测量各种健康指标，代谢产物和基因表达特征。限制叶酸的摄入减少了小鼠的合成代谢过程，增强了代谢可塑性。尽管叶酸摄入量有限的小鼠血清叶酸水平降低，但这些动物在生命后期保持了体重和肥胖，我们没有观察到不良的健康结果。这些结果表明，叶酸饮食干预的有效性可能会因个人的年龄和性别而异。在生命的早期阶段，较高的叶酸摄入量有利于支持正常发育所需的细胞分裂。然而，在以后的生活中摄入较低的叶酸可能会导致更健康的衰老。
Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual’s age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.