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Muscle Loss (muscle + loss)
Selected AbstractsKidney Function as a Predictor of Loss of Lean Mass in Older Adults: Health, Aging and Body Composition StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2007Linda F. Fried MD OBJECTIVES: To assess the association between kidney function and change in body composition in older individuals. DESIGN: Prospective cohort study. SETTING: Two sites, Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Three thousand twenty-six well-functioning, participants aged 70 to 79 in the Health, Aging and Body Composition Study. MEASUREMENTS: Body composition (bone-free lean mass and fat mass) was measured using dual x-ray absorptiometry annually for 4 years. Kidney function was measured at baseline according to serum creatinine (SCr). Comorbidity and inflammatory markers were evaluated as covariates in mixed-model, repeated-measures analysis. RESULTS: High SCr was associated with loss of lean mass in men but not women, with a stronger relationship in black men (P=.02 for difference between slopes for white and black men). In white men, after adjustment for age and comorbidity, higher SCr remained associated with loss of lean mass (,0.07±0.03 kg/y greater loss per 0.4 mg/dL (1 standard deviation (SD)), P=.009) but was attenuated after adjustment for inflammatory factors (,0.05±0.03 kg/y greater loss per SD, P=.10). In black men, the relationship between SCr and loss of lean mass (,0.19±0.04 kg/y per SD, P<.001) persisted after adjustment for inflammation and overall weight change. CONCLUSION: Impaired kidney function may contribute to loss of lean mass in older men. Inflammation appeared to mediate the relationship in white but not black men. Future studies should strive to elucidate mechanisms linking kidney disease and muscle loss and identify treatments to minimize loss of lean mass and its functional consequences. [source] Effects of myostatin deletion in aging miceAGING CELL, Issue 5 2009Michael R. Morissette Summary Inhibitors of myostatin, a negative regulator of skeletal muscle mass, are being developed to mitigate aging-related muscle loss. Knock-out (KO) mouse studies suggest myostatin also affects adiposity, glucose handling and cardiac growth. However, the cardiac consequences of inhibiting myostatin remain unclear. Myostatin inhibition can potentiate cardiac growth in specific settings (Morissette et al., 2006), a concern because of cardiac hypertrophy is associated with adverse clinical outcomes. Therefore, we examined the systemic and cardiac effects of myostatin deletion in aged mice (27,30 months old). Heart mass increased comparably in both wild-type (WT) and KO mice. Aged KO mice maintained twice as much quadriceps mass as aged WT; however, both groups lost the same percentage (36%) of adult muscle mass. Dual-energy X-ray absorptiometry revealed increased bone density, mineral content, and area in aged KO vs. aged WT mice. Serum insulin and glucose levels were lower in KO mice. Echocardiography showed preserved cardiac function with better fractional shortening (58.1% vs. 49.4%, P = 0.002) and smaller left ventricular diastolic diameters (3.41 vs. 2.71, P = 0.012) in KO vs. WT mice. Phospholamban phosphorylation was increased 3.3-fold in KO hearts (P < 0.05), without changes in total phospholamban, sarco(endo)plasmic reticulum calcium ATPase 2a or calsequestrin. Aged KO hearts showed less fibrosis by Masson's Trichrome staining. Thus, myostatin deletion does not affect aging-related increases in cardiac mass and appears beneficial for bone density, insulin sensitivity and heart function in senescent mice. These results suggest that clinical interventions designed to inhibit skeletal muscle mass loss with aging could have beneficial effects on other organ systems as well. [source] Muscle precursor cells isolated from aged rats exhibit an increased tumor necrosis factor-, responseAGING CELL, Issue 1 2009Simon J. Lees Summary Improving muscle precursor cell (MPC, muscle-specific stem cells) function during aging has been implicated as a key therapeutic target for improving age-related skeletal muscle loss. MPC dysfunction during aging can be attributed to both the aging MPC population and the changing environment in skeletal muscle. Previous reports have identified elevated levels of tumor necrosis factor-, (TNF-,) in aging, both circulating and locally in skeletal muscle. The purpose of the present study was to determine if age-related differences exist between TNF-,-induced nuclear factor-kappa B (NF-,B) activation and expression of apoptotic gene targets. MPCs isolated from 32-month-old animals exhibited an increased NF-,B activation in response to 1, 5, and 20 ng mL,1 TNF-,, compared to MPCs isolated from 3-month-old animals. No age differences were observed in the rapid canonical signaling events leading to NF-,B activation or in the increase in mRNA levels for TNF receptor 1, TNF receptor 2, TNF receptor-associated factor 2 (TRAF2), or Fas (CD95) observed after 2 h of TNF-, stimulation. Interestingly, mRNA levels for TRAF2 and the cell death-inducing receptor, Fas (CD95), were persistently upregulated in response to 24 h TNF-, treatment in MPCs isolated from 32-month-old animals, compared to 3-month-old animals. Our data indicate that age-related differences may exist in the regulatory mechanisms responsible for NF-,B inactivation, which may have an effect on TNF-,-induced apoptotic signaling. These findings improve our understanding of the interaction between aged MPCs and the changing environment associated with age, which is critical for the development of potential clinical interventions aimed at improving MPC function with age. [source] A pathomechanical concept explains muscle loss and fatty muscular changes following surgical tendon releaseJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004Dominik C. Meyer Abstract Following tendon tear, the musculo-tendinous unit retracts permanently, looses muscle fibre volume and is infiltrated with fat. This is currently considered to be an unexplained degenerative process. In a sheep model of chronic tendon tear with delayed tendon repair (35 weeks after tendon release), we studied the nature of these muscle changes in eight experimental animals. At sacrifice (75 weeks after tendon release) the muscle had retracted by 1.7±0.5 cm (9% of entire length, P < 0.0001), the pennation angle had increased from 22±2.5° to 50±11° (P < 0.0001) and the mean muscle fibre length had shortened from 32±3 to 16±5 mm (50%, P < 0.0001). In electron and light microscopy, we found essentially normal muscle fibres with an unaltered fibre diameter and myofibrillar structure, while interstitial fat and fibrous tissue had increased from 3.9% to 45.9% (P < 0.0001) of the muscle volume. Geometric modelling showed that the increase of the pennation angle separates the muscle fibre bundles mechanically like limbs of a parallelogram. Infiltrating fat cells fill the created space between the reoriented muscle fibres which may be quantitatively calculated without affecting the structural properties of the muscle cells. Fatty infiltration is therefore not seen as a degenerative process but a necessary rearrangement of the tissue after macroarchitectural changes caused by musculo-tendinous retraction. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Gene and protein expression associated with protein synthesis and breakdown in paraplegic skeletal muscleMUSCLE AND NERVE, Issue 4 2008Micah J. Drummond PhD Abstract Spinal cord injury reduces the rate of skeletal muscle protein synthesis and increases protein breakdown, resulting in rapid muscle loss. The purpose of this study was to determine whether long-term paraplegia would eventually result in a downregulation of muscle mRNA and protein expression associated with both protein synthesis and breakdown. After 10 weeks of spinal cord transection, soleus muscle from 12 rats (6 sham-control, 6 paraplegic) was studied for mRNAs and proteins associated with protein synthesis and breakdown using real-time polymerase chain reaction and immunoblotting techniques. Protein kinase B (PKB/Akt), ribosomal S6 kinase 1 (S6K1), and myogenin mRNA were downregulated, whereas muscle ring finger 1 (MuRF1) and phospho-forkhead transcription factor 4 (FoxO4) protein were increased in paraplegic rats. We conclude that gene and protein expression of pathways associated with protein synthesis are reduced, whereas some markers of protein breakdown remain elevated following chronic paraplegia. Clinical interventions designed to increase muscle protein synthesis may be helpful in preventing excessive muscle loss during long-term paraplegia. Muscle Nerve, 2008 [source] ORIGINAL RESEARCH,BASIC SCIENCE: Cavernous Neurotomy in the Rat is Associated with the Onset of an Overt Condition of HypogonadismTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2009Linda Vignozzi MD ABSTRACT Background., Most men following radical retropubic prostatectomy (RRP) are afflicted by erectile dysfunction (ED). RRP-related ED occurs as a result of surgically elicited neuropraxia, leading to histological changes in the penis, including collagenization of smooth muscle and endothelial damage. Aim., To verify whether hypogonadism could contribute to the pathogenesis of RRP-ED. Methods., Effects of testosterone (T), alone or in association with long-term tadalafil (Tad) treatment in a rat model of bilateral cavernous neurotomy (BCN). Main Outcome Measures., Penile tissues from rats were harvested for vasoreactivity studies 3 months post-BCN. Penile oxygenation was evaluated by hypoxyprobe immunostaining. Phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expression were quantified by Real Time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results., In BCN rats, we observed the onset of an overt condition of hypogonadism, characterized by reduced T plasma level, reduced ventral prostate weight, reduced testis function (including testis weight and number of Leydig cells), with an inadequate compensatory increase of luteinizing hormone. BCN induced massive penile hypoxia, decreased muscle/fiber ratio, nNOS, eNOS, PDE5 expression, increased sensitivity to the nitric oxide donor, sodium nitroprusside (SNP), and reduced the relaxant response to acetylcholine (Ach), as well as unresponsiveness to acute Tad dosing. In BCN rats, chronic Tad-administration normalizes penile oxygenation, smooth muscle loss, PDE5 expression, SNP sensitivity, and the responsiveness to the acute Tad administration. Chronic Tad treatment was ineffective in counteracting the reduction of nNOS and eNOS expression, along with Ach responsiveness. T supplementation, in combination with Tad, reverted some of the aforementioned alterations, restoring smooth muscle content, eNOS expression, as well as the relaxant response of penile strips to Ach, but not nNOS expression. Conclusion., BCN was associated with hypogonadism, probably of central origin. T supplementation in hypogonadal BCN rats ameliorates some aspects of BCN-induced ED, including collagenization of penile smooth muscle and endothelial dysfunction, except surgically induced altered nNOS expression.Vignozzi L, Filippi S, Morelli A, Marini M, Chavalmane A, Fibbi B, Silvestrini E, Mancina R, Carini M, Vannelli GB, Forti G, and Maggi M. Cavernous neurotomy in the rat is associated with the onset of an overt condition of hypogonadism. J Sex Med 2009;6:1270,1283. [source] Constitutive activation of MAPK cascade in acute quadriplegic myopathyANNALS OF NEUROLOGY, Issue 2 2004Simone Di Giovanni MD Acute quadriplegic myopathy (AQM; also called "critical illness myopathy") shows acute muscle wasting and weakness and is experienced by some patients with severe systemic illness, often associated with administration of corticosteroids and/or neuroblocking agents. Key aspects of AQM include muscle atrophy and myofilament loss. Although these features are shared with neurogenic atrophy, myogenic atrophy in AQM appears mechanistically distinct from neurogenic atrophy. Using muscle biopsies from AQM, neurogenic atrophy, and normal controls, we show that both myogenic and neurogenic atrophy share induction of myofiber-specific ubiquitin/proteosome pathways (eg, atrogin-1). However, AQM patient muscle showed a specific strong induction of transforming growth factor (TGF),,/MAPK pathways. Atrophic AQM myofibers showed coexpression of TGF-, receptors, p38 MAPK, c-jun, and c-myc, including phosphorylated active forms, and these same fibers showed apoptotic features. Our data suggest a model of AQM pathogenesis in which stress stimuli (sepsis, corticosteroids, pH imbalance, osmotic imbalance) converge on the TGF-, pathway in myofibers. The acute stimulation of the TGF-,/MAPK pathway, coupled with the inactivity-induced atrogin-1/proteosome pathway, leads to the acute muscle loss seen in AQM patients. Ann Neurol 2004 [source] Phylogenetic Relationships of the Suborders of Coleoptera (Insecta)CLADISTICS, Issue 1 2000Rolf G. Beutel One hundred seven external and internal characters of larval and adult representatives of 28 genera of the coleopteran suborders were analyzed cladistically. Four groups of Neuropterida were introduced as outgroup. The analysis yielded 18 trees with a minimum of 194 steps (CI 0.691). All trees support the monophyly of all four suborders and a branching pattern (Archostemata + (Adephaga + (Myxophaga + Polyphaga))). The presence of elytra with meso- and metathoracic locking devices, the specific hind-wing folding, the close connection of exposed sclerites, the absence of the mera, the absence of eight thoracic muscles, the reduced abdominal sternite I, and the invagination of terminal segments are autapomorphies of Coleoptera. The monophyly of Coleoptera excl. Archostemata is supported by further transformations of the thoracic sclerites such as absence of the mesothoracic discriminal line and katepisternal joint, by an internalized or absent metathoracic trochantin, by the presence of a bending zone in the hind-wing, and by eight further muscle losses. Fusion of tibia and tarsus and presence of a single claw are larval synapomorphies of Myxophaga and Polyphaga. Adults are characterized by fusion of protrochantin and propleura and by the rigid connection of the meso- and metathoracic ventrites. The eucinetoid lineage of Polyphaga is characterized by the secondary absence of the bending zone of the alae. This results in a distinctly simplified wing folding mechanism. The monophyly of Cucujiformia (+ Bostrichoidea) is supported by the presence of cryptonephric Malpighian tubules. Transformations of fore-and hind-wings, reinforcement and simplification of the thoracic exoskeleton, and an efficient use of a distinctly reduced set of thoracic muscles play an important role in the early evolution of Coleoptera. Many different larval character transformations take place in the earlier Mesozoic within the suborders. [source] | |||||||||||||