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Maternal α-casein deficiency extends the lifespan of offspring and programmes their body composition
GeroScience ( IF 5.3 ) Pub Date : 2024-07-12 , DOI: 10.1007/s11357-024-01273-2
Andreas F Kolb 1 , Claus Mayer 2 , Alina Zitskaja 1 , Linda Petrie 1 , Khulod Hasaballah 1 , Claire Warren 3 , Ailsa Carlisle 3 , Simon Lillico 3 , Bruce Whitelaw 3
Affiliation  

Early nutrition has significant effects on physiological outcomes during adult life. We have analysed the effect of maternal α-casein (CSN1S1) deficiency on the physiological fate of dams and their offspring. α-casein deficiency reduces maternal milk protein concentration by more than 50% and attenuates the growth of pups to 27% (p < 0.001) of controls at the point of weaning. This is associated with a permanent reduction in adult body weight (− 31% at 25 weeks). Offspring nursed by α-casein deficient dams showed a significantly increased lifespan (+ 20%, χ2: 10.6; p = 0.001). Liver transcriptome analysis of offspring nursed by α-casein deficient dams at weaning revealed gene expression patterns similar to those found in dwarf mice (reduced expression of somatotropic axis signalling genes, increased expression of xenobiotic metabolism genes). In adult mice, the expression of somatotropic axis genes returned to control levels. This demonstrates that, in contrast to dwarf mice, attenuation of the GH-IGF signalling axis in offspring nursed by α-casein deficient dams is transient, while the changes in body size and lifespan are permanent. Offspring nursed by α-casein deficient dams showed permanent changes in body composition. Absolute and relative adipose tissue weights (p < 0.05), the percentage of body fat (p < 0.001) as well as adipocyte size in epididymal white adipose tissue are all reduced. Serum leptin levels were 25% of those found in control mice (p < 0.001). Liver lipid content and lipid composition were significantly altered in response to postnatal nutrition. This demonstrates the nutrition in early life programmes adult lipid metabolism, body composition and lifespan.



中文翻译:


母体 α-酪蛋白缺乏症可延长后代的寿命并调整其身体成分



早期营养对成年期间的生理结果具有显着影响。我们分析了母体 α-酪蛋白 (CSN1S1) 缺乏对母鼠及其后代生理命运的影响。断奶时,α-酪蛋白缺乏会使母乳蛋白浓度降低 50% 以上,并使幼仔的生长速度降低至对照组的 27% ( p < 0.001)。这与成人体重的永久性减轻有关(25 周时体重减轻 31%)。由缺乏 α-酪蛋白的母鼠喂养的后代的寿命显着延长 (+ 20%, χ 2 : 10.6; p = 0.001)。对断奶时α-酪蛋白缺陷母鼠哺育的后代进行的肝脏转录组分析显示,基因表达模式与侏儒小鼠相似(生长轴信号基因的表达减少,外源代谢基因的表达增加)。在成年小鼠中,生长轴基因的表达恢复到控制水平。这表明,与侏儒小鼠相比,α-酪蛋白缺陷母鼠所哺育的后代中 GH-IGF 信号轴的减弱是暂时的,而体型和寿命的变化是永久性的。由缺乏α-酪蛋白的母鼠哺育的后代表现出身体成分的永久性变化。绝对和相对脂肪组织重量( p < 0.05)、体脂百分比( p < 0.001)以及附睾白色脂肪组织中的脂肪细胞大小均减少。血清瘦素水平是对照小鼠的 25% ( p < 0.001)。肝脏脂质含量和脂质成分因产后营养而显着改变。这表明生命早期的营养会影响成人的脂质代谢、身体成分和寿命。

更新日期:2024-07-12
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