Life-long caloric restriction reveals biphasic and dimorphic effects on bone metabolism in rodents
Life-long caloric restriction reveals biphasic and dimorphic effects on bone metabolism in rodents
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DOI：
10.1210/en.2007-1089
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发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
Ikeda, Kyoji
中科院分区：
文献类型：
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作者：
Tatsumi, Sawako;Ito, Masako;Ikeda, Kyoji
热量限制（CR）延长了各种生物体的寿命，减缓了年龄相关疾病的发作;然而，关于CR本身对骨骼的长期影响知之甚少。在本研究中，我们研究了终身CR与随意（AD）喂养的影响，主要是对雄性C57 BL/ 6小鼠和F344大鼠近端胫骨的骨小梁的影响。胫骨的微型计算机断层扫描显示，CR 3-9个月导致三维骨体积大幅减少，结构紊乱。骨组织形态计量学显示骨量减少主要是由于骨形成受到抑制。在瘦素受体缺陷的db/ db小鼠中，CR不能降低骨量和抑制骨形成。CR对骨量的影响被β-肾上腺素能受体阻滞剂普萘洛尔抑制。因此，CR可能通过瘦素信号传导和交感神经张力升高来调节骨形成。有趣的是，CR和AD组之间的骨体积差异在1岁后消失，并且CR额外延长至自然死亡的小鼠和大鼠保持比AD组更高的骨量，骨转换减少，表明CR通过调节骨转换速率来减缓骨骼衰老。据我们所知，这是第一份报告，研究了终身CR对骨代谢和骨小梁显微结构的影响，并记录了其在成熟期与成熟后，退化期的对比效应。
Caloric restriction (CR) extends the lifespan of various organisms and slows the onset of age-related disorders; however, little is known about the long-term effects of CR per se on bone. In the present study, we have examined the effects of life-long CR vs. ad libitum (AD) feeding, mainly on the trabecular bone of proximal tibiae in male C57BL/ 6 mice and F344 rats. Micro-computed tomography scanning of tibiae revealed that CR for 3-9 months caused a substantial decrease in three-dimensional bone volume with structural derangements. Bone histomorphometry revealed the reduced bone mass was due mainly to suppression of bone formation. In db/ db mice with defective leptin receptor, CR was unable to decrease bone mass and suppress bone formation. The effect of CR on bone mass was inhibited by administration of a beta-adrenergic renergic blocker, propranolol. Thus, CR may regulate bone formation through leptin signaling and elevated sympathetic nervous tone. Interestingly, the difference in bone volume between the CR and AD groups disappeared after 1 yr of age, and mice and rats on an additional extension of CR to natural death maintained higher bone mass than the AD groups, with reduced bone turnover, suggesting that CR slows skeletal aging by regulating the rate of bone turnover. This is the first report, to our knowledge, that has examined the effects of lifelong CR on bone metabolism and trabecular microstructure and documents its contrasting effects during maturation vs. the postmaturational, involutional period.