Peer-reviewed article
Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming in mice
Yeyu Song, Jingyi Xu, Jingjie Zhao, Rong Yang, 马援第 et al. ·
Summary
Written by AI, not yet AICS's view · claude-sonnet-5-5This is a laboratory study in mice, not in children. It tested whether overfeeding in the newborn period leads to faster muscle loss (sarcopenia) and metabolic problems in old age. The authors report that overfed mice lived shorter lives and lost more muscle late in life. They link this to lasting damage to the gut's mucus barrier and a loss of the gut bacterium Akkermansia muciniphila. Restoring the bacterium or giving its by-product acetate improved muscle function in aged mice. The authors suggest early-life nutrition may matter for healthy ageing, but the findings are not tested in human children.
Key points
- Neonatal overfeeding accelerated age-related sarcopenia in mice of both sexes.
- Early overnutrition shortened lifespan and worsened late-life muscle atrophy, alongside metabolic dysfunction.
- Overfeeding disrupted goblet cell development, causing lasting mucus barrier defects and reduced A. muciniphila colonisation during ageing.
- Fecal microbiota transplantation transferred the sarcopenic phenotype.
- A. muciniphila reconstitution or acetate supplementation restored muscle mitochondrial homeostasis and improved muscle performance in aged mice.
Limitations
The work is in mice only, so it cannot show that the same effects occur in human children or what a safe feeding level would be. The abstract gives no numbers, sample sizes or detail on the study methods.
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. Here, the authors demonstrate that neonatal overfeeding in mice shortens lifespan and accelerates late-life muscle loss. This originates from persistent gut mucus defects and depleted Akkermansia muciniphila, revealing a targetable developmental origin for sarcopenia.