Murray Samuel S, Duarte Maria Eugenia L, Brochmann Elsa J
Geriatric Research Education and Clinical Center, Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA.
Metabolism. 2003 Aug;52(8):970-7. doi: 10.1016/s0026-0495(03)00164-1.
Dietary restriction (DR) increases the life span and retards the development of age-related disorders. However, the low body mass that accompanies DR is associated with risk factors for fracture that may outweigh the beneficial effects of DR on cellular aging that are mediated, in part, by limiting free radical generation and oxidative damage. We tested the effects of DR in murine models that differ in free radical generation capacity (SENCAR > C57 > DBA). Male mice of each strain were killed at 10 weeks of age (t(0); time zero) or randomized to an ad libitum-fed (AL-fed) or 30% DR feeding regimen for 6 months. The food consumption of AL-fed mice was measured daily. DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. The DR diet was normalized with respect to calcium (Ca), phosphorus (P), and micronutrients. Lean body mass (LBM), bone mineral density (BMD), and bone mineral content (BMC) in the humerus and mandible were determined by PIXImus densitometry. The length and midshaft width of the humerus were determined by direct measurement. There were highly strain- and diet/time-dependent effects on LBM, humerus length, mandibular and humeral BMD, and humeral BMC. The interaction between diet/time and strain was more significant in the humerus than the mandible. All 30% DR mice had lower humeral BMDs and BMCs than their respective AL-fed controls. However, 30% DR C57 and DBA (but not SENCAR) mice had higher humeral BMD and BMC than their respective t(0) controls. There was a linear relationship between LBM and humeral BMD and BMC in both AL-fed and 30% DR mice, suggesting that the lower BMD and BMC in 30% DR mice, relative to AL-fed controls, reflects a physiologic adaptation to lower biomechanical loading. Mandibular BMC in 30% DR C57 (but not DBA or SENCAR) mice was lower than that observed in their AL-fed controls. Mandibular BMD and BMC increased versus t(0) values in 30% DR mice of all strains.
饮食限制（DR）可延长寿命并延缓与年龄相关疾病的发展。然而，DR伴随的低体重与骨折风险因素相关，这些风险因素可能超过DR对细胞衰老的有益影响，而这种有益影响部分是通过限制自由基生成和氧化损伤来介导的。我们在自由基生成能力不同的小鼠模型（SENCAR > C57 > DBA）中测试了DR的效果。每种品系的雄性小鼠在10周龄时（t(0)；零时间）处死，或随机分为自由采食（AL-fed）或30% DR喂养方案，持续6个月。每天测量AL-fed小鼠的食物消耗量。DR小鼠前一天接受其各自AL-fed小鼠食物消耗量的70%。DR饮食在钙（Ca）、磷（P）和微量营养素方面进行了标准化。通过PIXImus骨密度仪测定肱骨和下颌骨的瘦体重（LBM）、骨矿物质密度（BMD）和骨矿物质含量（BMC）。通过直接测量确定肱骨的长度和中轴宽度。LBM、肱骨长度、下颌骨和肱骨BMD以及肱骨BMC存在高度品系和饮食/时间依赖性效应。饮食/时间与品系之间的相互作用在肱骨中比在下颌骨中更显著。所有30% DR小鼠的肱骨BMD和BMC均低于其各自的AL-fed对照。然而，30% DR C57和DBA（但不是SENCAR）小鼠的肱骨BMD和BMC高于其各自的t(0)对照。在AL-fed和30% DR小鼠中，LBM与肱骨BMD和BMC之间存在线性关系，这表明相对于AL-fed对照，30% DR小鼠中较低的BMD和BMC反映了对较低生物力学负荷的生理适应。30% DR C57（但不是DBA或SENCAR）小鼠的下颌骨BMC低于其AL-fed对照。所有品系的30% DR小鼠下颌骨BMD和BMC相对于t(0)值均增加。
