Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming in mice
Abstract
Early-life nutrition shapes lifelong health, yet the long-term consequences of childhood overnutrition, particularly on musculoskeletal aging, remain unclear. Here, we show that neonatal overfeeding acts as a developmental insult that accelerates age-related sarcopenia in both sexes. Using different mouse models, early overnutrition shortens lifespan and exacerbates late-life muscle atrophy, accompanied by metabolic dysfunction. Mechanistically, neonatal overfeeding disrupts goblet cell development, leading to persistent mucus barrier defects and consequently reduced Akkermansia muciniphila (A. muciniphila) colonization during aging. Fecal microbiota transplantation transfers the sarcopenic phenotype, implicating gut dysbiosis in disease propagation. Loss of A. muciniphila reduces acetate production, impairs muscle mitochondrial function at least in part via suppressed GPR43 signaling, and aggravates sarcopenia. Conversely, A. muciniphila reconstitution or acetate supplementation restores mitochondrial homeostasis and improves muscle performance in aged mice. These findings reveal a developmental origin of age-related sarcopenia and define a gut-muscle axis linking early-life overnutrition to muscle aging, highlighting the preventive potential of optimizing early nutrition to support healthy aging.
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BibTeX
@article{song2026neonatal,
title = {{Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming in mice}},
author = {Yeyu Song and Jingyi Xu and Jingjie Zhao and Rong Yang and Yuandi Ma and Yi-Ming Hou and Yutang Cao and Jiaqi Li and Shuwu Yu and Xinyu Liang and Yongxin Zhang and Kanglong Wang and Lijuan An and Yameng Liu and Zhuo-Xian Meng and Jian-Gao Fan and Cen Xie},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78216-2},
url = {https://www.nature.com/articles/s41467-026-78216-2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming in mice
AU - Yeyu Song
AU - Jingyi Xu
AU - Jingjie Zhao
AU - Rong Yang
AU - Yuandi Ma
AU - Yi-Ming Hou
AU - Yutang Cao
AU - Jiaqi Li
AU - Shuwu Yu
AU - Xinyu Liang
AU - Yongxin Zhang
AU - Kanglong Wang
AU - Lijuan An
AU - Yameng Liu
AU - Zhuo-Xian Meng
AU - Jian-Gao Fan
AU - Cen Xie
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-78216-2
UR - https://www.nature.com/articles/s41467-026-78216-2
AB - Early-life nutrition shapes lifelong health, yet the long-term consequences of childhood overnutrition, particularly on musculoskeletal aging, remain unclear. Here, we show that neonatal overfeeding acts as a developmental insult that accelerates age-related sarcopenia in both sexes. Using different mouse models, early overnutrition shortens lifespan and exacerbates late-life muscle atrophy, accompanied by metabolic dysfunction. Mechanistically, neonatal overfeeding disrupts goblet cell development, leading to persistent mucus barrier defects and consequently reduced Akkermansia muciniphila (A. muciniphila) colonization during aging. Fecal microbiota transplantation transfers the sarcopenic phenotype, implicating gut dysbiosis in disease propagation. Loss of A. muciniphila reduces acetate production, impairs muscle mitochondrial function at least in part via suppressed GPR43 signaling, and aggravates sarcopenia. Conversely, A. muciniphila reconstitution or acetate supplementation restores mitochondrial homeostasis and improves muscle performance in aged mice. These findings reveal a developmental origin of age-related sarcopenia and define a gut-muscle axis linking early-life overnutrition to muscle aging, highlighting the preventive potential of optimizing early nutrition to support healthy aging.
SN - 2041-1723
ER -