Early-life nutrition influences thymic growth in male mice that may be related to the regulation of longevity
Early-life nutrition influences thymic growth in male mice that may be related to the regulation of longevity
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DOI：
10.1042/cs20090429
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发表时间：
2010-03-01
期刊：
影响因子：
6
通讯作者：
Ozanne, Susan E.
中科院分区：
文献类型：
--
作者：
Chen, Jian-Hua;Tarry-Adkins, Jane L.;Ozanne, Susan E.
生命早期的营养和生长速度会影响以后的健康和寿命。我们以前已经证明，低出生体重，导致母亲在怀孕期间的蛋白质限制，然后在啮齿动物追赶增长，与缩短寿命，而蛋白质限制和哺乳期增长缓慢增加寿命。这些差异产生的潜在机制尚不清楚。在本研究中，我们报告说，母体蛋白质限制在小鼠胸腺生长的影响在成年早期的生活。在哺乳期喂食低蛋白饮食的母鼠的后代（PLP后代）在21天至12周龄期间具有显著的胸腺生长，而在对照小鼠或妊娠期喂食低蛋白饮食的母鼠的后代（恢复后代）中未观察到这一点。与对照组相比，PLP小鼠（P < 0.001和P < 0.05）和恢复期小鼠（P <0.001和P <0.01）胸腺中增殖细胞核抗原（PCNA）和沉默信息调节因子1（SIRT 1）蛋白水平在2 ~ 1日龄均显著升高。在12周时，PLIP小鼠保持较高的SIRT 1水平，而恢复后代的胸腺中PCNA减少。这表明，有丝分裂活动最初在PLP和恢复后代的胸腺中增强，但仅在PLP小鼠中保持到成年。PLP和恢复小鼠胸腺中的有丝分裂活性差异似乎受到性激素浓度和p53、p16、雄激素受体、IL-7（白细胞介素-7）和IL-7受体表达变化的影响。总之，胸腺生长差异可能有助于调节长寿的母亲的饮食。
Nutrition and growth rate during early life can influence later health and lifespan. We have demonstrated previously that low birthweight, resulting from maternal protein restriction during pregnancy followed by catch-up growth in rodents, was associated with shortened lifespan, whereas protein restriction and slow growth during lactation increased lifespan. The underlying mechanisms by which these differences arise are unknown. In the present study, we report that maternal protein restriction in mice influences thymic growth in early adult life. Offspring of dams fed a low-protein diet during lactation (PLP offspring) had significant thymic growth from 21 days to 12 weeks of age, whereas this was not observed in control mice or offspring of dams fed a low-protein diet during pregnancy (recuperated offspring). PCNA (proliferating-cell nuclear antigen) and SIRT1 (silent information regulator 1) protein levels at 2 1 days of age were significantly higher in the thymus from both PLP mice (P < 0.001 and P < 0.05 respectively) and recuperated mice (P < 0.001 and P < 0.01 respectively) compared with controls. At 12 weeks, PLIP mice maintained a higher SIRT1 level, whereas PCNA was decreased in the thymus from recuperated offspring. This suggests that mitotic activity was initially enhanced in the thymus from both PLP and recuperated offspring, but remained sustained into adulthood only in PLP mice. The differential mitotic activity in the thymus from PLP and recuperated mice appeared to be influenced by changes in sex hormone concentrations and the expression of p53, p 16, the androgen receptor, IL-7 (interleukin-7) and the IL-7 receptor. In conclusion, differential thymic growth may contribute to the regulation of longevity by maternal diet.