The benefits of increased human lifespan depend upon duration of healthy, independent living; the healthspan. Bone-wasting disorders contribute significantly to loss of independence, frailty, and morbidity in older people. Therefore, there is an unmet need globally for lifestyle interventions to reduce the likelihood of bone fractures with age. Although many mechanisms are involved in disorders of bone loss, there is no single regulatory pathway and, therefore, there is no single treatment available to prevent their occurrence. Our aim in these studies was to determine whether fasting/feeding interventions alter the effect of mechanical loading on bone anabolic activities and increase bone mass. In young 17-week-old mice, 16-hour fasting period followed by reintroduction of food for 2 hours increased markedly the potency of mechanical loading, that mimics the effect of exercise, to induce new cortical bone formation. Consistent with this finding, fasting and re-feeding increased the response of bone to a loading stimulus that, alone, does not stimulate new bone formation in ad-lib fed mice. Older mice (20 months) experienced no potentiation of loading-induced bone formation with the same timing of feeding interventions. Interestingly, the pre-, prandial, and postprandial endocrine responses in older mice were different from those in young animals. The hormones that change in response to timing of feeding have osteogenic effects that interact with loading-mediated effects. Our findings indicate associations between timing of food ingestion and bone adaptation to loading. If translated to humans, such non-pharmacological lifestyle interventions may benefit skeletal health of humans throughout life-course and in older age.

中文翻译：

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喂养干预增强机械负荷诱导小鼠新骨形成的作用

延长人类寿命的好处取决于健康、独立生活的持续时间；健康跨度。骨质流失疾病显着导致老年人丧失独立性、虚弱和患病。因此，全球对生活方式干预的需求未得到满足，以减少随着年龄增长骨折的可能性。尽管许多机制涉及骨质流失疾病，但没有单一的调节途径，因此，没有单一的治疗方法可以预防它们的发生。我们在这些研究中的目的是确定禁食/​​进食干预是否会改变机械负荷对骨合成代谢活动的影响并增加骨量。在 17 周大的年轻小鼠中，禁食 16 小时，然后重新引入食物 2 小时，机械负荷的效力显着增加，模仿运动的效果，诱导新的皮质骨形成。与这一发现一致，禁食和重新喂食增加了骨骼对负荷刺激的反应，这种刺激单独不会刺激即兴喂养小鼠的新骨形成。年龄较大的小鼠（20 个月）在喂养干预的时间相同的情况下没有经历负荷诱导的骨形成的增强。有趣的是，老年小鼠的餐前、餐前和餐后内分泌反应与年轻动物不同。响应喂食时间而变化的激素具有与负荷介导的作用相互作用的成骨作用。我们的研究结果表明食物摄入时间与骨骼对负荷的适应之间存在关联。如果翻译成人类，