| Title: | Maternal aging increases offspring adult body size via transmission of donut-shaped mitochondria |
| Journal: | Cell Research |
| Published: | 27 Jul 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37500768/ |
| DOI: | https://doi.org/10.1038/s41422-023-00854-8 |
| URL: | https://www.nature.com/articles/s41422-023-00854-8.pdf |
Publication 11652
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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.</p>
16 Authors
- Runshuai Zhang
- Jinan Fang
- Ting Qi
- Shihao Zhu
- Luxia Yao
- Guicun Fang
- Yunsheng Li
- Xiao Zang
- Weina Xu
- Wanyu Hao
- Shouye Liu
- Dan Yang
- Di Chen
- Jian Yang
- Xianjue Ma
- Lianfeng Wu
1 Application
| Application ID | Title |
|---|---|
| 66982 | Identifying genetic and environmental factors underpinning complex trait variation in humans |
Enabling scientific discoveries that improve human health