西湖大学Lianfeng Wu、Xianjue Ma和Jian Yang等取得一项新成果。经过不懈努力，他们发现母体衰老通过传播“甜甜圈”形线粒体来增加后代成年后的体型。相关论文于2023年7月27日发表于国际学术期刊《细胞研究》杂志上。

使用成年体型作为主要参数，研究人员揭示了母亲而非父亲的生育年龄对人类、果蝇和秀丽隐杆线虫后代成年特征的影响，并且具有进化保守。在人类和其他长寿动物中阐明这种作用机制仍具有挑战，因为它们的寿命长并且难以进行体内研究。因此，研究人员利用寿命短且遗传可操纵的秀丽隐杆线虫来探究母体衰老调节后代成虫性状的机制。

通过微观分析，研究发现年老线虫将“甜甜圈“状的衰老线粒体传递给后代。这些线粒体在后代发育早期恢复活力，它们的形态在成年前以AMPK依赖的方式得到恢复。从机制上讲，研究人员证明早期线粒体功能障碍激活AMPK，这反过来不仅减弱了线粒体异常，而且还激活了TGFβ信号传导以增加后代成年体型的大小。总之，该研究结果为母体衰老在塑造后代成年特征中的作用机制提供了见解。

据介绍，近几十年来，产妇的生育年龄逐年增加。然而，尚不清除它是否以及如何影响后代的成年特征。

附：英文原文

Title: Maternal aging increases offspring adult body size via transmission of donut-shaped mitochondria

Author: Zhang, Runshuai, Fang, Jinan, Qi, Ting, Zhu, Shihao, Yao, Luxia, Fang, Guicun, Li, Yunsheng, Zang, Xiao, Xu, Weina, Hao, Wanyu, Liu, Shouye, Yang, Dan, Chen, Di, Yang, Jian, Ma, Xianjue, Wu, Lianfeng

Issue&Volume: 2023-07-27

Abstract: Maternal age at childbearing has continued to increase in recent decades. However, whether and how it influences offspring adult traits are largely unknown. Here, using adult body size as the primary readout, we reveal that maternal rather than paternal age has an evolutionarily conserved effect on offspring adult traits in humans, Drosophila, and Caenorhabditis elegans. Elucidating the mechanisms of such effects in humans and other long-lived animals remains challenging due to their long life course and difficulties in conducting in vivo studies. We thus employ the short-lived and genetically tractable nematode C. elegans to explore the mechanisms underlying the regulation of offspring adult trait by maternal aging. By microscopic analysis, we find that old worms transmit aged mitochondria with a donut-like shape to offspring. These mitochondria are rejuvenated in the offspring’s early life, with their morphology fully restored before adulthood in an AMPK-dependent manner. Mechanistically, we demonstrate that early-life mitochondrial dysfunction activates AMPK, which in turn not only alleviates mitochondrial abnormalities but also activates TGFβ signaling to increase offspring adult size. Together, our findings provide mechanistic insight into the ancient role of maternal aging in shaping the traits of adult offspring.

DOI: 10.1038/s41422-023-00854-8

Source: https://www.nature.com/articles/s41422-023-00854-8