Volume 33, No 11, Nov 2023

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 33 Issue 11, November 2023: 821-834   |  Open Access

ORIGINAL ARTICLES

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

Runshuai Zhang^{1,2,3,4,5,†} , Jinan Fang^1,2,3,4,† , Ting Qi^1,2,† , Shihao Zhu^1,2,3,4,5 , Luxia Yao^1,2,3,4,5 , Guicun Fang⁶ , Yunsheng Li^1,2 , Xiao Zang⁷ , Weina Xu^1,2,3,4,5 , Wanyu Hao^1,2,3,4,5 , Shouye Liu^1,2,8 , Dan Yang^1,2 , Di Chen⁷ , Jian Yang^1,2,* , Xianjue Ma^1,2,3,4,* , Lianfeng Wu^1,2,3,4,5,*

¹Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
²School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
³Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, Hangzhou, Zhejiang, China
⁴Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China
⁵Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
⁶Microscopy Core Facility, Westlake University, Hangzhou, Zhejiang, China
⁷Model Animal Research Center of Medical School, Nanjing University, Nanjing, Jiangsu, China
⁸Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, QLD, Australia
^†These authors contributed equally: Runshuai Zhang, Jinan Fang, Ting Qi
Correspondence: Jian Yang(jian.yang@westlake.edu.cn)Xianjue Ma(maxianjue@westlake.edu.cn)Lianfeng Wu(wulianfeng@westlake.edu.cn)

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.

https://doi.org/10.1038/s41422-023-00854-8

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