Cardiovascular Research Institute, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya, Saitama-City, Saitama, Japan.
Amino Acids. 2020 Feb;52(2):213-224. doi: 10.1007/s00726-019-02733-2. Epub 2019 Apr 19.
The polyamines spermidine and spermine are synthesized in almost all organisms and are also contained in food. Polyamine synthesis decreases with aging, but no significant decrease in polyamine concentrations were found in organs, tissues, and blood of adult animals and humans. We found that healthy dietary patterns were associated with a preference for polyamine-rich foods, and first reported that increased polyamine intake extended the lifespan of mice and decreased the incidence of colon cancer induced by repeated administration of moderate amounts of a carcinogen. Recent investigations have revealed that changes in DNA methylation status play an important role in lifespan and aging-associated pathologies. The methylation of DNA is regulated by DNA methyltransferases in the presence of S-adenosylmethionine. Decarboxylated S-adenosylmethionine, converted from S-adenosylmethionine by S-adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize spermine and spermidine and acts to inhibit DNMT activity. Long-term increased polyamine intake were shown to elevate blood spermine levels in mice and humans. In vitro studies demonstrated that spermine reversed changes induced by the inhibition of ornithine decarboxylase (e.g., increased decarboxylated S-adenosylmethionine, decreased DNA methyltransferase activity, increased aberrant DNA methylation), whose activity decreases with aging. Further, aged mice fed high-polyamine chow demonstrated suppression of aberrant DNA methylation and a consequent increase in protein levels of lymphocyte function-associated antigen 1, which plays a pivotal role on inflammatory process. This review discusses the relation between polyamine metabolism and DNA methylation, as well as the biological mechanism of lifespan extension induced by increased polyamine intake.
多胺亚精胺和精胺几乎在所有生物体中合成，也存在于食物中。多胺合成随年龄增长而减少，但在成年动物和人体的器官、组织和血液中并未发现多胺浓度有明显下降。我们发现健康的饮食模式与多胺丰富的食物偏好有关，并且首次报道增加多胺摄入可以延长小鼠的寿命，并降低反复给予适量致癌物引起的结肠癌的发生率。最近的研究表明，DNA 甲基化状态的变化在寿命和与衰老相关的病理中起着重要作用。DNA 的甲基化受 S-腺苷甲硫氨酸存在时的 DNA 甲基转移酶的调节。脱羧 S-腺苷甲硫氨酸由 S-腺苷甲硫氨酸脱羧酶从 S-腺苷甲硫氨酸转化而来，为合成精胺和亚精胺提供一个氨基丙基，并作用于抑制 DNMT 活性。长期增加多胺摄入可使小鼠和人体血液中的精胺水平升高。体外研究表明，精胺逆转了由于抑制鸟氨酸脱羧酶而引起的变化（例如，脱羧 S-腺苷甲硫氨酸增加、DNA 甲基转移酶活性降低、异常 DNA 甲基化增加），鸟氨酸脱羧酶的活性随年龄增长而降低。此外，喂食高多胺饮食的老年小鼠表现出异常 DNA 甲基化的抑制以及淋巴细胞功能相关抗原 1 蛋白水平的升高，淋巴细胞功能相关抗原 1 在炎症过程中起着关键作用。这篇综述讨论了多胺代谢与 DNA 甲基化之间的关系，以及增加多胺摄入延长寿命的生物学机制。
