Dean Pomerleau Posted November 24, 2015 Report Share Posted November 24, 2015 Here is another gem of a study  from James Cain latest weekly CR research update (thanks James!) worth its own thread. In this study, the researchers subjected mice to pretty severe (40%) CR either starting very young (4 weeks) or starting late in life (48 or 68 weeks). CR started in the oldest mice (68 weeks) and lasting for 12 weeks had negative effects on their bone health. When CR was started young (4 weeks), there was an initial period when the bone health of the CR'ed mice was profoundly compromised, both in terms of bone mineral density and force required to break the femur. But over the lifetime of the early-onset CR'ed mice, their bone health improved markedly, both in terms bone mineral density and the microarchitecture of the bone. In short, the bones of mice who started CR at a young age were light but strong when they got old. That is comforting, and accords with the finding  from Luigi Fontana on some of us human calorie restrictors that our bones are healthy despite long-term CR. --Dean ---------  J Bone Miner Res. 2015 Nov 17. doi: 10.1002/jbmr.2745. [Epub ahead of print] Dietary Restriction-Induced Alterations in Bone Phenotype: Effects of LifelongVersus Short-Term Caloric Restriction on Femoral and Vertebral Bone in C57BL/6Mice.Behrendt AK(1,)(2), Kuhla A(2), Osterberg A(3), Polley C(2), Herlyn P(1), FischerDC(4), Scotland M(1), Wree A(5), Histing T(6), Menger MD(7), Müller-Hilke B(3),Mittlmeier T(1), Vollmar B(2).Caloric restriction (CR) is a well-described dietary intervention that delays theonset of aging-associated biochemical and physiological changes thereby extendingthe lifespan of rodents. The influence of CR on metabolism, strength andmorphology of bone has been controversially discussed in literature. Thus, thepresent study evaluated whether lifelong CR versus short-term late-onset dietaryintervention differentially affects the development of senile osteoporosis inC57BL/6 mice. Two different dietary regimens with 40% food restriction wereperformed: lifelong CR starting in 4wk-old mice was maintained for 4, 20 or 74weeks. In contrast, short-term late-onset CR lasting a period of 12 weeks wascommenced at 48 or 68 weeks of age. Control mice were fed ad libitum (AL). Bonespecimens were assessed using microcomputed tomography (µCT, femur and lumbarvertebral body) and biomechanical testing (femur). Adverse effects of CR,including reduced cortical bone mineral density (Ct.BMD) and thickness (Ct.Th)were detected to some extent in senile mice (68 + 12w) but in particular incortical bone of young growing mice (4 + 4w), associated with reduced femoralfailure force (F). However, we observed a profound capacity of bone to compensatethese deleterious changes of minor nutrition with increasing age presumably viareorganization of trabecular bone. Especially in lumbar vertebrae, lifelong CRlasting 20 or 74 weeks had beneficial effects on trabecular bone mineral density(Tb.BMD), bone volume fraction (BV/TV) and trabecular number (Tb.N). In parallel,lifelong CR groups showed reduced structure model index values compared toage-matched controls indicating a transformation of vertebral trabecular bonemicroarchitecture towards a plate-like geometry. This effect was not visible insenile mice after short-term 12-week CR. In summary, CR has differential effectson cortical and trabecular bone dependent on bone localization and starting age.Our study underlines that bone compartments possess a lifelong capability to copewith changing nutritional influences. This article is protected by copyright. Allrights reserved.This article is protected by copyright. All rights reserved.PMID: 26572927 -------------------  Aging Cell. 2011 Feb;10(1):96-102. doi: 10.1111/j.1474-9726.2010.00643.x. Epub 2010 Nov 15. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition. Villareal DT(1), Kotyk JJ, Armamento-Villareal RC, Kenguva V, Seaman P, Shahar A, Wald MJ, Kleerekoper M, Fontana L. Author information: (1)Division of Geriatrics and Nutritional Science, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. Calorie restriction (CR) reduces bone quantity but not bone quality in rodents. Nothing is known regarding the long-term effects of CR with adequate intake of vitamin and minerals on bone quantity and quality in middle-aged lean individuals. In this study, we evaluated body composition, bone mineral density (BMD), and serum markers of bone turnover and inflammation in 32 volunteers who had been eating a CR diet (approximately 35% less calories than controls) for an average of 6.8 ± 5.2 years (mean age 52.7 ± 10.3 years) and 32 age- and sex-matched sedentary controls eating Western diets (WD). In a subgroup of 10 CR and 10 WD volunteers, we also measured trabecular bone (TB) microarchitecture of the distal radius using high-resolution magnetic resonance imaging. We found that the CR volunteers had significantly lower body mass index than the WD volunteers (18.9 ± 1.2 vs. 26.5 ± 2.2 kg m(-2) ; P = 0.0001). BMD of the lumbar spine (0.870 ± 0.11 vs. 1.138 ± 0.12 g cm(-2) , P = 0.0001) and hip (0.806 ± 0.12 vs. 1.047 ± 0.12 g cm(-2) , P = 0.0001) was also lower in the CR than in the WD group. Serum C-terminal telopeptide and bone-specific alkaline phosphatase concentration were similar between groups, while serum C-reactive protein (0.19 ± 0.26 vs. 1.46 ± 1.56 mg L(-1) , P = 0.0001) was lower in the CR group. Trabecular bone microarchitecture parameters such as the erosion index (0.916 ± 0.087 vs. 0.877 ± 0.088; P = 0.739) and surface-to-curve ratio (10.3 ± 1.4 vs. 12.1 ± 2.1, P = 0.440) were not significantly different between groups. These findings suggest that markedly reduced BMD is not associated with significantly reduced bone quality in middle-aged men and women practicing long-term calorie restriction with adequate nutrition. PMCID: PMC3607368 PMID: 20969721 Link to comment Share on other sites More sharing options...
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