小柯机器人

美国威尔康奈尔医学中心John Blenis和Ana P. Gomes课题组宣布他们发现随年龄增加，甲基丙二酸积累促进肿瘤进展。2020年8月19日出版的《自然》在线发表了这项成果。

在本研究中，研究人员发现随着年龄增长，代谢改变会产生有利于肿瘤进展和侵袭的系统环境。具体而言，研究发现丙二酸代谢的副产物甲基丙二酸（MMA）在老年人的血清中增加，并可作为肿瘤进展的介质。研究人员认为这是由于MMA诱导SOX4表达并因此引发转录重编程，这使得癌细胞具有攻击性。因此，MMA的积累代表了衰老和癌症进展之间的关联，这表明MMA可能是治疗晚期癌症的潜在靶点。

据了解，从65岁起，人们患癌症的风险和相关死亡率大大增加。尽管如此，人类对年龄与癌症之间复杂关系的理解仍处于起步阶段。几十年来，年龄与癌症间的联系很大程度上归因于老年人暴露于诱变剂的时间增加。然而，这种观点并不能说明饮食、运动和预防新陈代谢退化小分子的作用。

附：英文原文

Title: Age-induced accumulation of methylmalonic acid promotes tumour progression

Author: Ana P. Gomes, Didem Ilter, Vivien Low, Jennifer E. Endress, Juan Fernndez-Garca, Adam Rosenzweig, Tanya Schild, Dorien Broekaert, Adnan Ahmed, Melanie Planque, Ilaria Elia, Julie Han, Charles Kinzig, Edouard Mullarky, Anders P. Mutvei, John Asara, Rafael de Cabo, Lewis C. Cantley, Noah Dephoure, Sarah-Maria Fendt, John Blenis

Issue&Volume: 2020-08-19

Abstract: The risk of cancer and associated mortality increases substantially in humans from the age of 65 years onwards1–6. Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy2,3,7,8. For decades, this link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the established role of diet, exercise and small molecules that target the pace of metabolic ageing9–12. Here we show that metabolic alterations that occur with age can produce a systemic environment that favours the progression and aggressiveness of tumours. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is upregulated in the serum of older people and functions as a mediator of tumour progression. We traced this to the ability of MMA to induce SOX4 expression and consequently to elicit transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, the accumulation of MMA represents a link between ageing and cancer progression, suggesting that MMA is a promising therapeutic target for advanced carcinomas. Ageing in humans is associated with an increase in circulating methylmalonic acid, which induces expression of SOX4 and promotes tumour progression.

DOI: 10.1038/s41586-020-2630-0

Source: https://www.nature.com/articles/s41586-020-2630-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html