Changes in blood bone markers after the first and second bouts of whole-body eccentric exercises.

The present study compared the first (EC1) and second (EC2) bouts of whole-body eccentric exercises to examine the effects of the magnitude of muscle damage on changes in blood bone markers. Fifteen sedentary young men performed nine eccentric exercises of arm, leg, and trunk muscles, and repeated them 2 weeks later. Blood samples were taken before and 2 h and 1-5 days following each bout to analyze plasma creatine kinase (CK) activity and myoglobin concentration, serum tartrate-resistant acid phosphatase (TRAP), type 1 C-terminal telopeptide (CTX-1), procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BAP), undercarboxylated-osteocalcin (ucOCN), carboxylated-osteocalcin (cOCN), and leptin concentrations. All except ucOCN changed significantly (p < 0.05) after both bouts. When comparing bouts for peak changes, P1NP (bone formation marker) and CTX-1 (bone resorption marker) increased less after EC2 (peak: 137±96% and 7±6%, respectively) than after EC1 (146 ± 80% and 30 ± 21%, respectively), whereas BAP (bone formation marker) increased more after EC2 (18 ± 16%) than after EC1 (4 ± 15%) (p < 0.05). Leptin (49 ± 58%) and cOCN (14 ± 10%) increased more (p < 0.05) after EC2 than after EC1 (-30 ± 15%, 9 ± 26%). Significant (p < 0.05) correlations were evident between peak CK activity and peak CTX-1 (r = 0.847), P1NP (r = 0.815), BAP (r = -0.707), ucOCN (r = 0.627), cCON (r = -0.759), and leptin (r = -0.740) changes after EC1, but many of these correlations disappeared after EC2. This was also found for the relationships between other muscle damage markers (myoglobin, muscle soreness, and muscle strength) and the bone markers. It was concluded that bone turnover was affected by eccentric exercise, but muscle damage was unfavorable for bone formation.

Changes in plasma C1q, apelin and adropin concentrations in older adults after descending and ascending stair walking intervention.

This study compared changes in plasma complement component 1q (C1q), apelin and adropin concentrations in older obese women after descending (DSW) and ascending stair walking (ASW) training (n = 15/group) performed twice a week for 12 weeks, with gradual increases in exercise time from 5 to 60 min. Fasting blood samples were collected 3 days before the first and 4 days after the last training session. The improvements in the maximal voluntary isometric contraction (MVIC) strength of the knee extensors, functional physical fitness [e.g., 30-s chair stand (CS) performance], resting systolic blood pressure (SBP), insulin sensitivity [e.g., oral glucose tolerance test (OGTT)] and blood lipid profiles [e.g., total cholesterol (TC)] were greater (p < 0.05) in the DSW than ASW group. Plasma C1q decreased (- 51 ± 30%), and apelin (23 ± 15%) and adropin (127 ± 106%) increased (p ≤ .0.05) only after DSW. Significant (p ≤ 0.01) partial correlations were found between the pre- to post-DSW changes in C1q, apelin or adropin and changes in outcome measures [e.g., C1q and MVIC (r = - 0.837), apelin and SBP (r = - 0.854), and andropin and OGTT (r = - 0.729)]. These results showed that greater decreases in plasma C1q and greater increases in apelin and adropin concentrations were associated with greater improvements in outcome measures after DSW than after ASW.

Acute responses of bone specific and related markers to maximal eccentric exercise of the knee extensors and flexors in young men.

OBJECTIVES: The present study determined time-course changes in plasma bone-specific and -related markers following a bout of maximal eccentric contractions (MaxEC) of bilateral knee extensors (KE) and flexors (KF). METHODS: Sedentary young men (n=30) performed a bout of 10 sets of 10 MaxEC (30°/s) of KE and KF with each leg, respectively. Maximal voluntary isometric contraction (MVC) torque, muscle soreness (SOR), plasma creatine kinase (CK) activity, insulin, leptin, tumor necrosis factor-α (TNF-α), undercarboxylated-osteocalcin (ucOCN), carboxy-terminal crosslinking telopeptide of type I collagen (CTX-1) and procollagen type I N-terminal propeptide (P1NP) concentrations were measured from before to 7 days after MaxEC. RESULTS: Significant changes in MVC (KE: -28%, KF: -38%), SOR and plasma CK activity (peak: 39,163 IU/L) following MaxEC were evident (P<0.05) compared to baseline. Plasma leptin (17%) concentrations decreased at 1 day after MaxEC. In bone related markers, plasma ucOCN concentrations (20%) increased at 7 days after MaxEC, and plasma CTX-1 concentrations decreased at 2, 4 and 7 days after MaxEC (6~7%; P<0.05). CONCLUSION: These results demonstrate that a lean effect of bone generation and an enhanced energy anabolism can be induced by a single bout of MaxEC.

The effects of a 226-km ironman triathlon race on bone turnover in amateur male triathletes.

BACKGROUND: The purpose of this study was to investigate the effects of an Ironman-distance triathlon on bone metabolism. METHODS: Nine recreational male triathletes (39.7±8.2 years old) were voluntarily recruited before a 226-km Ironman triathlon race. Baseline blood samples were collected >1 hour before race. Serial post-race blood sampling time points included immediately (0hr), 1 hour (1hr), 1 day (d), 3 d, and 5 d after the Ironman race. RESULTS: Serum muscle damage markers, serum myoglobin, creatine kinase (CK) and lactate dehydrogenase (LDH) revealed significant post-race peak values immediately, 1hr and 1d after the race, respectively. Except for the marginally higher serum CK and myoglobin at 5d (P=0.01~0.05), all post-race serum levels of muscle damage markers were significantly higher than baseline levels (P<0.01). Serum phosphorus values were significantly higher immediately (0hr) after the Ironman race. Serum osteocalcin, an index specific to bone formation, showed a significant decrease at time points 0hr and 1hr, but a significant increase 1 day after (P<0.01) and a marginal increase 3 and 5 days after (P=0.01~0.05) the race. No difference was shown in type I collagen C-telopeptide (CTX-1), a bone resorption marker. Pearson's correlation between serum osteocalcin and CTX-1 was done at each time point, and significant correlation was shown on the 5th d after the race (r=0.591, P<0.05). CONCLUSIONS: An Ironman-distance contest induces a bone-formative-favoring turnover during the post-race period for amateur male triathletes.

Differences in neurocognitive performance and metabolic and inflammatory indices in male adults with obesity as a function of regular exercise.

NEW FINDINGS: What is the central question of this study? Does regular exercise have benefits with regard to the neurocognitive problems related to obesity and are regular-exercise-induced neurocognitive changes associated with changes in the levels of metabolic/inflammatory biomarkers? What is the main finding and its importance? Although obese individuals with regular exercise showed higher C-reactive protein levels as compared to the healthy-weight individuals, only the obese individuals with a sedentary lifestyle showed deviant neurocognitive performance and higher metabolic and tumour necrosis factor-α levels. The P3 amplitude was correlated with the levels of leptin in the obese individuals with regular activity, implicating that the potential mechanism of neurocognitive facilitation as a result of regular exercise could be reduced serum leptin levels. ABSTRACT: Obesity has been shown to be highly associated with deterioration in executive functions, elevated energy metabolic indices and low-grade systemic inflammation. Exercise has the capacity to reduce these negative phenomena. This work examined the effect of regular exercise on neurocognitive deficits and metabolic/inflammatory markers in obesity. Fifty-four participants were divided into three groups: healthy-weight (HW), obesity with regular exercise (ORE) and obesity with sedentary lifestyle (OSL), according to their BMI and frequency of exercise. Dual-energy X-ray absorptiometry was applied to assess the whole-body composition of the participants. The assessment included neurocognitive measures during the Posner paradigm test and fasting blood measurements. Relative to the HW group, only the OSL group showed significantly longer reaction times and smaller P3 amplitudes, even when controlling for the cardiorespiratory fitness co-variable. Although the OSL group exhibited a greater N2 amplitude than the HW group, when controlling for cardiorespiratory fitness the difference between the two groups disappeared. The OSL group showed greater levels of metabolic indices (i.e. leptin, insulin and glucose) than the HW group. The three groups had comparable interleukin (IL)-1ß and IL-6 levels. However, the ORE and OSL groups showed higher levels of C-reactive protein than the HW group. The OSL group exhibited higher tumour necrosis factor-α levels than the HW and ORE groups. P3 amplitude was negatively correlated with the levels of leptin in the ORE group. Individuals with obesity can still obtain advantages with regard to neurocognitive and metabolic/inflammatory indices through engaging in regular exercise, possibly due to reduced serum leptin levels.

Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production.

Chronic kidney disease-mineral bone disorder (CKD-MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/ß-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial ß-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.

Structural and Biomechanical Adaptations to Free-Fall Landing in Hindlimb Cortical Bone of Growing Female Rats.

The purpose of the study was to investigate the adaptation process of hindlimb cortical bone subjected to free-fall landing training. Female Wistar rats (7 weeks old) were randomly assigned to four landing (L) groups and four age-matched control (C) groups (n = 12 per group): L1, L2, L4 L8, C1, C2, C4 and C8. Animals in the L1, L2, L4 and L8 groups were respectively subjected to 1, 2, 4 and 8 weeks of free-fall-landing training (40 cm height, 30 times/day and 5 days/week) while the C1, C2, C4 and C8 groups served as age-matched control groups. The tibiae of the L8 group were higher in cortical bone mineral content (BMC) than those in the C8 group (p < 0.05). Except for the higher bone mineralization over bone surface ratio (MS/BS, %) shown in the tibiae of the L1 group (p < 0.05), dynamic histomorphometry in the tibial and femoral cortical bone showed no difference between landing groups and their age-matched control groups. In the femora, the L1 group was lower than the C1 group in cortical bone area (Ct.Ar) and cortical thickness (Ct.Th) (p < 0.05); however, the L4 group was higher than the C4 group in Ct.Ar and Ct.Th (p <0 .05). In the tibiae, the moment of inertia about the antero-posterior axis (Iap), Ct.Ar and Ct.Th was significantly higher in the L8 group than in the C8 group (p < 0.05). In biomechanical testing, fracture load (FL) of femora was lower in the L1 group than in the C1 group (p < 0.05). Conversely, yield load (YL), FL and yield load energy (YE) of femora, as well as FL of tibiae were all significantly higher in the L8 group than in the C8 group (p < 0.05). Free-fall landing training may initially compromise bone material. However, over time, the current free-fall landing training induced improvements in biomechanical properties and/or the structure of growing bones.

Neurocognitive performances of visuospatial attention and the correlations with metabolic and inflammatory biomarkers in adults with obesity.

NEW FINDINGS: What is the central question of this study? Obesity is linked to cognitive deficits, elevated energy metabolic indices and low-grade systemic inflammation. Do the relationships between neurocognitive performance and the biochemical markers (e.g. energy metabolic indices and inflammatory cytokines) occur independently of factors known to be associated with neurocognitive dysfunction (i.e. cardiorespiratory fitness) in young adults? What is the main finding and its importance? Young obese adults showed poorer neuropsychological performances, aberrant neural activity and higher C-reactive protein and energy metabolic indices. The higher leptin and C-reactive protein concentrations showed a significant negative association with lower P3 amplitudes. However, leptin was the sole predictive factor, implicating hyperleptinaemia in the altered neurocognitive function observed in obesity. The present study was designed to explore the neurophysiological mechanism of visuospatial attention deficits in obese adults and to examine the relationships between neurocognitive (neuropsychological and neurophysiological) performances and the biochemical markers. Thirty obese adults and 30 healthy-weight control subjects, categorized by body mass index and percentage fat as measured with dual-energy X-ray absorptiometry, provided a fasting blood sample and performed a visuospatial attention protocol with concomitant electrophysiological recording. The obese group showed slower reaction times and smaller P3 amplitudes when performing the cognitive task. Even when controlling for the covariable of cardiorespiratory fitness, the results remained. In addition, the serum concentrations of insulin, glucose, leptin and C-reactive protein were significantly higher in the obese group relative to the control group, but not those of interleukin-6, interleukin-1ß and tumour necrosis factor-α. Partial correlations adjusting for cardiorespiratory fitness showed that leptin and C-reactive protein concentrations in the obese group were negatively associated with poorer neurophysiological (i.e. P3 amplitude) performance. However, the regression analysis showed that leptin was the sole predictor of P3 amplitude in the obese group. These findings indicate that the individuals with obesity exhibited neurocognitive deficits when performing the visuospatial attention task, and serum leptin concentrations could be one of the influential factors.

Exercise training ameliorates glucosamine-induced insulin resistance in ovariectomized rats.

OBJECTIVE: Glucosamine (GlcN), which has been reported to induce insulin resistance (IR), is a popular nutritional supplement used to treat osteoarthritis in menopausal women. We previously demonstrated that GlcN treatment caused IR in ovariectomized rats by reducing the expression of glucose transport protein subtype 4 (GLUT-4) in skeletal muscle. In the present study, we hypothesized that endurance exercise training can reverse GlcN-induced IR. METHODS: Fifty female rats were randomly divided into five groups with 10 rats in each group: (1) sham-operated group; (2) sham-operated group with GlcN treatment for 14 days; (3) ovariectomy (OVX) group; (4) OVX with GlcN treatment; and (5) OVX with GlcN treatment followed by exercise training (running program) for 8 weeks. RESULTS: Fasting plasma glucose increased in the OVX + GlcN group, and fasting plasma insulin and the homeostasis model assessment-insulin resistance (HOMA-IR) were significantly higher only in this group. After the rats received exercise training for 8 weeks, no increase in the fasting plasma glucose, insulin, or HOMA-IR was observed. In an intraperitoneal glucose tolerance test, the plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index were significantly elevated only in the OVX with GlcN treatment group. However, the plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index decreased after exercise training for 8 weeks, implying that GlcN-induced IR in OVX rats could be reversed through exercise. A histological analysis revealed that exercise training can reduce islet hypertrophy and maintain GLUT-4 in skeletal muscle. CONCLUSIONS: Exercise training can alleviate IR in OVX rats treated with GlcN. Islet hyperplasia was subsequently prevented. Preserving GLUT-4 expression may be one of the mechanisms by which exercise prevents IR.

Dietary restrictions, bone density, and bone quality.

Caloric restriction (CR), protein restriction (PR), and specific amino acid restriction (e.g., methionine restriction (MR)) are different dietary interventions that have been confirmed with regard to their comprehensive benefits to metabolism and health. Based on bone densitometric measurements, weight loss induced by dietary restriction is known to be accompanied by reduced areal bone mineral density, bone mass, and/or bone size, and it is considered harmful to bone health. However, because of technological advancements in bone densitometric instruments (e.g., high-resolution X-ray tomography), dietary restrictions have been found to cause a reduction in bone mass/size rather than volumetric bone mineral density. Furthermore, when considering bone quality, bone health consists of diverse indices that cannot be fully represented by densitometric measurements alone. Indeed, there is evidence that moderate dietary restrictions do not impair intrinsic bone material properties, despite the reduction in whole-bone strength because of a smaller bone size. In the present review, we integrate research evidence from traditional densitometric measurements, metabolic status assays (e.g., energy metabolism, oxidative stresses, and inflammatory responses), and biomaterial analyses to provide revised conclusions regarding the effects of CR, PR, and MR on the skeleton.

Methionine restriction alters bone morphology and affects osteoblast differentiation.

Methionine restriction (MR) extends the lifespan of a wide variety of species, including rodents, drosophila, nematodes, and yeasts. MR has also been demonstrated to affect the overall growth of mice and rats. The objective of this study was to evaluate the effect of MR on bone structure in young and aged male and female C57BL/6J mice. This study indicated that MR affected the growth rates of males and young females, but not aged females. MR reduced volumetric bone mass density (vBMD) and bone mineral content (BMC), while bone microarchitecture parameters were decreased in males and young females, but not in aged females compared to control-fed (CF) mice. However, when adjusted for bodyweight, the effect of MR in reducing vBMD, BMC and microarchitecture measurements was either attenuated or reversed suggesting that the smaller bones in MR mice is appropriate for its body size. In addition, CF and MR mice had similar intrinsic strength properties as measured by nanoindentation. Plasma biomarkers suggested that the low bone mass in MR mice could be due to increased collagen degradation, which may be influenced by leptin, IGF-1, adiponectin and FGF21 hormone levels. Mouse preosteoblast cell line cultured under low sulfur amino acid growth media attenuated gene expression levels of Col1al, Runx2, Bglap, Alpl and Spp1 suggesting delayed collagen formation and bone differentiation. Collectively, our studies revealed that MR altered bone morphology which could be mediated by delays in osteoblast differentiation.

Effects of methionine restriction and endurance exercise on bones of ovariectomized rats: a study of histomorphometry, densitometry, and biomechanical properties.

To investigate the effects of dietary methionine restriction (MetR) and endurance exercise on bone quality under a condition of estrogen deficiency, female Sprague-Dawley rats (36-wk-old) were assigned to a sham surgery group or one of five ovariectomized groups subjected to interventions of no treatment (Ovx), endurance exercise (Exe), methionine restriction (MetR), methionine restriction plus endurance exercise (MetR + Exe), and estrogen treatment (Est). Rats in the exercise groups were subjected to a treadmill running regimen. MetR and control diets contained 0.172 and 0.86% methionine, respectively. After the 12-wk intervention, all animals were killed, and serum and bone tissues were collected for analyses. Compared with estrogen treatment, MetR diet and endurance exercise showed better or equivalent efficiency in reducing body weight gain caused by ovariectomy (P < 0.05). Whereas only the Est group showed evidence for reduced bone turnover compared with the Ovx group, MetR diet and/or endurance exercise demonstrated efficiencies in downregulating serum insulin, leptin, triglyceride, and thiobarbituric acid reactive substances (P < 0.05). Both the Exe and MetR groups showed higher femoral cortical and total volumetric bone mineral density (vBMD), but only the Exe and Est groups preserved cancellous bone volume and/or vBMD of distal femora (P < 0.05) compared with the Ovx group. After being normalized to body mass, femora of the MetR and MetR + Exe groups had relatively higher bending strength and dimension values followed by the Sham, Exe, and Est groups (P < 0.05). In conclusion, both MetR diet and endurance exercise improved cortical bone properties, but only endurance exercise preserved cancellous bone under estrogen deficiency.

Relationship between Fibroblast Growth Factor 23 and Biochemical and Bone Histomorphometric Alterations in a Chronic Kidney Disease Rat Model Undergoing Parathyroidectomy.

BACKGROUND: Phosphate burden in chronic kidney disease (CKD) leads to elevated serum fibroblast factor-23 (FGF-23) levels, secondary hyperparathyroidism and chronic kidney disease-mineral bone disorder (CKD-MBD). However dissociated hyperphosphatemia and low serum FGF-23 concentrations have been observed in experimentally parathyoridectomized rats. The relationships between serum mineral, hormone, and bone metabolism may be altered in the presence of CKD. The aim of our study was to investigate whether a consistent relationship existed between serum FGF-23 levels, specific serum biochemical markers, and histomorphometric parameters of bone metabolism in a parathyroidectomized CKD animal model. RESULTS: Sprague Dawley rats were divided into 3 groups: parathyroidectomy (PTX) and CKD (PTX+CKD, 9 rats), CKD without PTX (CKD, 9 rats), and neither PTX nor CKD (sham-operated control, 8 rats); CKD was induced by partial nephrectomy. At 8 weeks after partial nephrectomy, serum biomarkers were measured. Bone histomorphometries of the distal femoral metaphyseal bone were analyzed. The mean serum FGF-23 levels and mean bone formation rate were the highest in the CKD group and the lowest in the PTX+CKD group. Bone volume parameters increased significantly in the PTX+CKD group. Pearson's correlation revealed that serum FGF-23 levels associated with those of intact parathyroid hormone, phosphate, collagen type I C-telopeptide, and calcium. Univariate linear regression showed that serum FGF-23 values correlated with bone formation rate, bone volume, and osteoid parameters. Stepwise multivariate regression analysis revealed that circulating FGF-23 values were independently associated with bone volume and thickness (ß = -0.737; p < 0.001 and ß = -0.526; p = 0.006, respectively). Serum parathyroid hormone levels independently correlated with bone formation rate (ß = 0.714; p < 0.001) while collagen type I C-telopeptide levels correlated with osteoid parameter. CONCLUSION: Serum FGF-23 levels independently correlated with bone volume parameters in rats with experimentally induced CKD.

Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF.

Molecular regulators of osteoclast formation and function are an important area of research due to the central role of osteoclasts in bone resorption. Transcription factors such as MITF are essential for osteoclast generation by regulating expression of the genes required for cellular differentiation and resorptive function. We recently reported that histone deacetylase 7 (HDAC7) binds to and represses the transcriptional activity of MITF in osteoclasts, and that loss of HDAC7 in vitro accelerated osteoclastogenesis. In the current study, we extend this initial observation by showing that conditional deletion of HDAC7 in osteoclasts of mice leads to an in vivo enhancement in osteoclast formation, associated with increased bone resorption and lower bone mass. Expression of multiple MITF target genes is increased in bone marrow derived osteoclast cultures from the HDAC7 knockout mice. Interestingly, multiple regions of the HDAC7 amino-terminus can bind to MITF or exert repressive activity. Moreover, mutation or deletion of the HDAC7 conserved deacetylase catalytic domain had little effect on repressive function. These observations identify HDAC7 in osteoclasts as an important molecular regulator of MITF activity and bone homeostasis, but also highlight a gap in our understanding of exactly how HDAC7 functions as a corepressor.

Executive function and endocrinological responses to acute resistance exercise.

THIS STUDY HAD THE FOLLOWING TWO AIMS: First, to explore the effects of acute resistance exercise (RE, i.e., using exercise machines to contract and stretch muscles) on behavioral and electrophysiological performance when performing a cognitive task involving executive functioning in young male adults; Second, to investigate the potential biochemical mechanisms of such facilitative effects using two neurotrophic factors [i.e., growth hormone (GH) and insulin-like growth factor-1 (IGF-1)] and the cortisol levels elicited by such an exercise intervention mode with two different exercise intensities. Sixty young male adults were recruited and randomly assigned to a high-intensity (HI) exercise group, moderate-intensity (MI) exercise group, and non-exercise-intervention (NEI) group. Blood samples were taken, and the behavioral and electrophysiological indices were simultaneously measured when individuals performed a Go/No-Go task combined with the Erikson Flanker paradigm at baseline and after either an acute bout of 30 min of moderate- or high-intensity RE or a control period. The results showed that the acute RE could not only benefit the subjects' behavioral (i.e., RTs and accuracy) performance, as found in previous studies, but also increase the P3 amplitude. Although the serum GH and IGF-1 levels were significantly increased via moderate or high intensity RE in both the MI and HI groups, the increased serum levels of neurotrophic factors were significantly decreased about 20 min after exercise. In addition, such changes were not correlated with the changes in cognitive (i.e., behavioral and electrophysiological) performance. In contrast, the serum levels of cortisol in the HI and MI groups were significantly lower after acute RE, and the changes in cortisol levels were significantly associated with the changes in electrophysiological (i.e., P3 amplitude) performance. The findings suggest the beneficial effects of acute RE on executive functioning could be due to changes in arousal, possibly modulated by the serum cortisol levels.

The first international mini-symposium on methionine restriction and lifespan.

It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met) ingestion by rats extends lifespan (Orentreich et al., 1993). Since then, several studies have replicated the effects of dietary methionine restricted (MR) in delaying age-related diseases (Richie et al., 1994; Miller et al., 2005; Ables et al., 2012; Sanchez-Roman and Barja, 2013). We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY, September 2013. The goals were (1) to gather researchers with an interest in MR and lifespan, (2) to exchange knowledge, (3) to generate ideas for future investigations, and (4) to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH), and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones, and the adipose tissue were discussed. The symposium also emphasized the value of other species, e.g., the naked mole rat, Brandt's bat, and Drosophila, in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies (Figure 3).

A methionine-restricted diet and endurance exercise decrease bone mass and extrinsic strength but increase intrinsic strength in growing male rats.

Dietary methionine restriction (MR) has been suggested to be comparable to endurance exercise with respect to its beneficial effects on health. To further investigate the effects of MR and endurance exercise on growing bone, 7-wk-old male Sprague-Dawley rats were fed different l-methionine (Met)-containing diets with or without endurance exercise intervention (Ex; 0.86% Met, 0.52% Met, 0.17% Met, 0.86% Met-Ex, 0.52% Met-Ex, and 0.17% Met-Ex groups). After an 8-wk intervention period, exercise-trained rats had a 9.2% lower body weight (BW) than did sedentary rats (P < 0.05). Additionally, 0.17% Met-fed rats had 32% lower BW when compared with rats fed the other 2 diets (P < 0.05). Serum osteocalcin was lower in the 0.17% Met-Ex group compared with the other 2 exercise groups and the 0.17% Met group (P < 0.05). Serum concentrations of C-terminal telopeptide of type 1 collagen were lower in exercise-trained and 0.17% Met-fed rats than in sedentary rats and rats fed the other 2 diets (P < 0.05 for both). Rats fed the 0.17% Met diet had lower trabecular bone volume, bone mineralization activities, and bone mineral content (BMC; e.g., total, cortical, and spongy BMC) and bone mineral density (BMD; e.g., total and spongy BMD) indices compared with rats fed the other 2 diets (P < 0.05). Exercise-trained rats also had lower bone mineralization activity, trabecular osteoclast density, total BMC, cortical BMC, and total BMD compared with sedentary rats (P < 0.05). In total BMD, only the 0.17% Met-Ex group had values lower than the other 2 exercise groups and the 0.17% Met group (P < 0.05). Compared with rats fed the other 2 diets and sedentary rats, the femora of 0.17% Met-fed and exercise-trained rats, respectively, had smaller size and/or lower extrinsic strength but enhanced intrinsic biomechanical properties (P < 0.05). The results indicate that MR and endurance exercise caused lower whole bone mass, size, and/or strength but might enhance intrinsic bone strength.

Impact of acute aerobic exercise and cardiorespiratory fitness on visuospatial attention performance and serum BDNF levels.

The purpose of the current study was to explore various behavioral and neuroelectric indices after acute aerobic exercise in young adults with different cardiorespiratory fitness levels when performing a cognitive task, and also to gain a mechanistic understanding of the effects of such exercise using the brain-derived neurotrophic factor (BDNF) biochemical index. Sixty young adults were separated into one non-exercise-intervention and two exercise intervention (EI) (i.e., EIH: higher-fit and EIL: lower-fit) groups according to their maximal oxygen consumption. The participants' cognitive performances (i.e., behavioral and neuroelectric indices via an endogenous visuospatial attention task test) and serum BDNF levels were measured at baseline and after either an acute bout of 30min of moderate intensity aerobic exercise or a control period. Analyses of the results revealed that although acute aerobic exercise decreased reaction times (RTs) and increased the central Contingent Negative Variation (CNV) area in both EI groups, only the EIH group showed larger P3 amplitude and increased frontal CNV area after acute exercise. Elevated BDNF levels were shown after acute exercise for both EI groups, but this was not significantly correlated with changes in behavioral and neuroelectric performances for either group. These results suggest that both EI groups could gain response-related (i.e., RT and central CNV) benefits following a bout of moderate acute aerobic exercise. However, only higher-fit individuals could obtain particular cognition-process-related efficiency with regard to attentional resource allocation (i.e., P3 amplitude) and cognitive preparation processes (i.e., frontal CNV) after acute exercise, implying that the mechanisms underlying the effects of such exercise on neural functioning may be fitness dependent. However, the facilitating effects found in this work could not be attributed to the transient change in BDNF levels after acute exercise.

Bone morphogenetic proteins signal via SMAD and mitogen-activated protein (MAP) kinase pathways at distinct times during osteoclastogenesis.

To investigate the role of bone morphogenetic protein (BMP) signaling in osteoclastogenesis in vivo, we eliminated BMPRII in osteoclasts by creating a BMPRII(fl/fl);lysM-Cre mouse strain. Conditional knock-out (cKO) mice are osteopetrotic when compared with WT controls due to a decrease in osteoclast activity. Bone marrow macrophages (BMMs) isolated from cKO mice are severely inhibited in their capacity to differentiate into mature osteoclasts in the presence of M-CSF and receptor activator of NF-κB (RANK) ligand. We also show that BMP noncanonical (MAPK) and canonical (SMAD) pathways are utilized at different stages of osteoclast differentiation. BMP2 induces p38 phosphorylation in pre-fusion osteoclasts and increases SMAD phosphorylation around osteoclast precursor fusion. Phosphorylation of MAPKs was decreased in differentiated BMMs from cKO animals. Treating BMMs with the SMAD inhibitor dorsomorphin confirms the requirement for the canonical pathway around the time of fusion. These results demonstrate the requirement for BMP signaling in osteoclasts for proper bone homeostasis and also explore the complex signaling mechanisms employed by BMP signaling during osteoclast differentiation.

Short-term free-fall landing causes reduced bone size and bending energy in femora of growing rats.

The purpose of this study was to determine the effects of a mechanical loading course (short-term free-fall landing) on femoral geometry and biomechanical properties in growing rats. Thirty-two female Wistar rats (7-week-old) were randomly assigned to three groups: L30 (n = 11), L10 (n = 11) and CON (n = 10) groups. Animals in the L10 and L30 groups were subjected to a 5-day free-fall landing program in which animals were dropped from a height of 40cm 10 and 30 times per day, respectively. Landing ground reaction force (GRF) was measured on the 1(st) and 5(th) days of landing training. All animals were subjected to two fluorescent labeling injections on the days before and after the 5-day landing training. Three days after the last labeling injection, animals were sacrificed under deep anesthesia. Methods of dynamic histomorphometry, tissue geometry and tissue biomechanical measurements were used to investigate the response in femora. A significant decrease in peak GRF in the hind-limb was shown from day 1 to day 5. No significant difference was shown among groups in dynamic histomorphometry. Biomechanical property analyses showed significantly lower maximal energy and post-yield energy in the L10 and L30 groups as compared to the CON group (p < 0.05). Moreover, geometric measurements revealed that cross-sectional cortical areas and thicknesses were significantly lower in landing groups than in the CON group. Short-term (5-day) free-fall landing training resulted in minor compromised long bone tissue, as shown by reduced bending energy and cortical bone area but not in other mechanical properties or tissue measurements (e.g. weights and length) of growing female rats. Further studies would be valuable to investigate whether this compromised bone material represents the existence of a latency period in the adaptation of bone material to external mechanical loading. Key pointsShort-term free-fall landing causes compromised bone material as shown by reduced post-yield energy in long bones of rodents.The results of the current study suggest the existence of unsettled bone material after a short-term mechanical loading regime.The connection of the present animal study to the stress fractures occurring in young athletes needs to be clarified.