Developmental Endocrinology Branch, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, CRC, Room 1-3330, 10 Center Drive, MSC-1103, Bethesda, Maryland 20892-1103, USA.
J Endocrinol. 2011 Jan;208(1):59-67. doi: 10.1677/JOE-10-0302. Epub 2010 Oct 25.
The mammalian growth plate undergoes programmed senescence during juvenile life, causing skeletal growth to slow with age. We previously found that hypothyroidism in rats slowed both growth plate chondrocyte proliferation and growth plate senescence, suggesting that senescence is not dependent on age per se but rather on chondrocyte proliferation. However, one alternative explanation is that the observed slowing of growth plate senescence is a specific consequence of hypothyroidism. We reasoned that, if delayed senescence is a general consequence of growth inhibition, rather than a specific result of hypothyroidism, then senescence would also be slowed by other growth-inhibiting conditions. In this study, we therefore used tryptophan deficiency to temporarily inhibit growth in newborn rats for 4 weeks. We then allowed the animals to recover and studied the effects on growth plate senescence. We found that structural, functional, and molecular markers of growth plate senescence were delayed by prior tryptophan deficiency, indicating that the developmental program of senescence had occurred more slowly during the period of growth inhibition. Taken together with previous studies in hypothyroid rats, our findings support the hypothesis that delayed senescence is a general consequence of growth inhibition and hence that growth plate senescence is not simply a function of time per se but rather depends on growth.
哺乳动物生长板在幼年时经历程序性衰老，导致骨骼生长随年龄增长而减缓。我们之前发现，大鼠的甲状腺功能减退症会减缓生长板软骨细胞的增殖和生长板衰老，这表明衰老不是取决于年龄本身，而是取决于软骨细胞的增殖。然而，另一种解释是，观察到的生长板衰老的减缓是甲状腺功能减退症的特定后果。我们推断，如果延迟衰老只是生长抑制的一般后果，而不是甲状腺功能减退症的特定结果，那么其他生长抑制条件也会减缓衰老。在这项研究中，我们因此使用色氨酸缺乏症在新生大鼠中暂时抑制生长 4 周。然后，我们让动物恢复并研究对生长板衰老的影响。我们发现，生长板衰老的结构、功能和分子标志物被先前的色氨酸缺乏症所延迟，这表明在生长抑制期间，衰老的发育程序发生得更慢。与之前在甲状腺功能减退症大鼠中的研究相结合，我们的发现支持这样的假设，即延迟衰老只是生长抑制的一般后果，因此，生长板衰老不是简单地取决于时间本身，而是取决于生长。
