Human Achilles tendon glycation and function in diabetes Couppé, Christian; Svensson, Rene Brüggebusch; Kongsgaard, Mads ...
Journal of applied physiology,
2016-Jan-15, 2016-01-15, 20160115, Letnik:
120, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles ...tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly (n = 22) and well (n = 22) controlled diabetic patients, including healthy age-matched (45-70 yr) controls (n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effect of diabetes was explored by collapsing the diabetes groups (DB) compared with the controls. Skin collagen cross-linking lysylpyridinoline, hydroxylysylpyridinoline (136%, 80%, P < 0.01) and pentosidine concentrations (55%, P < 0.05) were markedly greater in DB. Furthermore, Achilles tendon material stiffness was higher in DB (54%, P < 0.01). Notably, DB also demonstrated higher forefoot/rearfoot peak-plantar-pressure ratio (33%, P < 0.01). Overall, Achilles tendon material stiffness and skin connective tissue cross-linking were greater in diabetic patients compared with controls. The higher foot pressure indicates that material stiffness of tendon and other tissue (e.g., skin and joint capsule) may influence foot gait. The difference in foot pressure distribution may contribute to the development of foot ulcers in diabetic patients.
Life-long regular endurance exercise yields positive effects on cardiovascular and metabolic function, disease and mortality rate. Glycation may be a major mechanism behind age-related diseases. ...However, it remains unknown if skin autofluorescence (SAF), which reflects glycation, is related to arterial and metabolic function in life-long endurance runners and sedentary controls.
Healthy elderly men: 15 life-long endurance runners (OT) (64±4years) and 12 old untrained (OU) (66±4years), and healthy young men; ten young athletes (YT) (26±4years) matched to OT for running distance, and 12 young untrained (YU) (24±3years) were recruited. Endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI@75 and AI) were measured by an operator-independent PAT 2000. SAF was non-invasively determined using an autofluorescence spectrometer.
For AI@75 there was an effect of age (p<0.0001), but not training (p=0.71). There was an interaction for endothelial function (p<0.05): YT had higher RHI than YU (p<0.05) and OU (p<0.01). SAF was associated with arterial stiffness (r2=0.57, p<0.001), insulin and HOMA-index levels after age correction (both r2=0.19, p<0.05).
To our knowledge, these are the first data to show that skin autofluorescence (SAF) is linked to human arterial stiffness and insulin resistance in well-trained elderly and young men as well as sedentary controls. SAF may in the future be a helpful tool to predict vascular and metabolic dysfunction (early signs of aging and pathology). Surprisingly, endurance running only had modest effects on cardiovascular function compared to lean healthy controls.
Resistance training is an effective strategy to counteract the age‐related loss of muscle mass and strength in elderly, but whether the benefits of training differ between sexes is unclear. A total ...of 297 elderly men and women were randomized to 1 year of heavy resistance training (HRT) or control (CON). Changes in muscle function and body composition were compared between sexes and groups. Improvements in muscle strength, body fat, muscle mass and size were observed, but the absolute improvements in muscle strength (23 Nm ± 2.3 vs 11 Nm ± 2.2, P < .01) and visceral fat content (−215 g ± 50 vs −60 g ± 21, P < .01) were greater in men. Also, the relative decrease in body fat % (−6.8% ± 1.1 vs −2.7% ± 0.7, P < .05) and fat mass (−7.9% ± 1.4 vs −2.7% ± 1.0, P < .05) was more pronounced in men. Heavy resistance training improved more than CON in most muscular and body composition parameters with greater increase in muscle strength and decrease in body fat in men. Consequently, resistance training is recommendable to counteract age‐related losses of muscle mass and strength and to reduce body fat in elderly, however, with a small advantage for men in parameters that predict metabolic risk factors.
Age-related loss of muscle mass and function can be attenuated in rodents with life-long voluntary wheel running with moderate resistance. The present study assessed if sarcopenia could be ...counteracted with ten weeks high intensity training.
Old (22–23 months) and middle-aged (11 months) mice were divided into three physical activity groups: Ten weeks of voluntary running in wheels with high (HR) or low resistance (LR), or no running wheel (SED). The wheel resistance was 0.5–1.5 g in the LR group and progressed from 5 g to 10 g in the HR group. Six, 8 and 5 old and 8, 9 and 9 middle-aged mice of the SED, LR and HR groups, respectively, were included in the analysis. Wheel activity was monitored throughout the intervention. Muscle mass of the tibialis anterior, gastrocnemius, soleus and plantaris muscles were measured post-mortem. Fiber type distribution and myofiber cross sectional areal (CSA) were quantified in the gastrocnemius and soleus muscles as well as total number of fibers in the soleus muscle.
In the SED, the mass of all individual muscles was reduced in the old vs middle-aged (P < 0.001). In the training groups, the old mice ran significantly less, slower and for shorter bouts than the middle-aged throughout the intervention (P < 0.05). HR running increased the gastrocnemius and soleus muscle mass by 6% and 18% respectively in the old compared to SED. Fiber CSA was significantly reduced in the old SED mice, whereas fiber CSA in the old HR gastrocnemius and soleus muscles was comparable to the SED middle-aged. Fiber type shifted from 2b towards 2a in the gastrocnemius muscle of the trained old mice. HR running was more efficient than LR in maintaining muscle mass and myofiber size, and in shifting fiber types. In the middle-aged mice, similar effects were found, but less pronounced. Interestingly, fiber CSA was unaffected by running in the middle-aged.
Ten weeks of HR running had a positive effect on muscle mass and morphology in both middle-aged and old mice. The old HR fiber CSA was greater than in old SED and comparable to the middle-aged, and the fibers shifted to a more oxidative composition (2b → 2a). Albeit less pronounced, similar training effects were observed in the middle-aged mice despite running faster and longer than the old.
•Ten weeks of high resistance wheel running can reverse age-related myofiber atrophy and loss of muscle mass in old mice.•Voluntary wheel running with low resistance for 10 weeks can attenuate, but not recover, age-related atrophy.•Wheel running is not sufficient to induce myofiber hypertrophy in middle-aged mice.
Fibrillin‐1 mutations cause pathological changes in connective tissue that constitute the complex phenotype of Marfan syndrome. In this study, we used fibrillin‐1 hypomorphic and haploinsufficient ...mice (Fbn1mgr/mgR and Fbn1+/− mice, respectively) to investigate the impact of fibrillin‐1 deficiency alone or in combination with regular physical activity on tendon tissue morphology and mechanical properties. Morphological and biomechanical analyses revealed that Fbn1mgr/mgR but not Fbn1+/− mice displayed smaller tendons with physical properties that were unremarkable when normalized to tendon size. Fbn1mgR/mgR mice (n = 43) Fbn1+/−mice (n = 27) and wild‐type mice (WT, n = 25) were randomly assigned to either control cage conditions (n = 54) or to a running on a running wheel for 4 weeks (n = 41). Both fibrillin‐1‐deficient mice ran voluntarily on the running wheel in a manner similar to WT mice (3–4 km/24 h). Regular exercise did not mitigate aneurysm progression in Fbn1mgR/mgR mice (P < 0.05) as evidenced by unmodified median survival. In spite of the smaller size, tendons of fibrillin‐1‐deficient mice subjected to regular exercise showed no evidence of overt histopathological changes or tissue overload. We therefore concluded that lack of optimal fibrillin‐1 synthesis leads to a down regulation of integrated tendon formation, rather than to a loss of tendon quality, which also implies that fibrillin‐1 deficiency in combination with exercise is not a suitable animal model for studying the development of tendon overuse (tendinopathy).
Regular exercise did not worsen or improve the median survival of Marfan syndrome mice, and they showed no signs of pathological changes in their tendons. Marfan syndrome mice had smaller tendons than wild type while the mechanical properties remained unchanged. Taken together, substantial fibrillin‐1 deficiency in Marfan syndrome does affect tendon quantity rather than quality regardless of regular exercise.
Conclusive insight into the microscopic principles that govern the strength of tendon and related connective tissues is lacking and the importance of collagen cross-linking has not been firmly ...established. The combined application of whole-tissue mechanical testing and atomic force spectroscopy allowed for a detailed characterization of the effect of cross-linking in rat-tail tendon. The cross-link inducing agent glutaraldehyde augmented the tensile strength of tendon fascicles. Stress at failure increased from ∼8 MPa to ∼39 MPa. The mechanical effects of glutaraldehyde at the tendon fibril level were examined by atomic force microscopy. Peak forces increased from ∼1379 to ∼2622 pN while an extended Hertz fit of force-indentation data showed a ∼24 fold increase in Young's modulus on indentation. The effect of glutaraldehyde cross-linking on the tensile properties of a single collagen fibril was investigated by a novel methodology based on atomic force spectroscopy. The Young's modulus of a secluded fibril increased from ∼407 MPa to ∼1.1 GPa with glutaraldehyde treatment. Collectively, the findings indicate that cross-linking at the level of the collagen fibril is of key importance for the mechanical strength of tendon tissue. However, when comparing the effects at the level of the tendon fascicle and fibril, respectively, further questions are prompted regarding the pathways of force through the tendon microstructure as fibril strength seems to surpass that of the tendon fascicle.
Purpose
Tendon force transmission depends on the length and mechanical behavior of collagen fibrils, two poorly understood parameters.
Methods
Collagen fibrils from rat‐tail tendons (RTT) and human ...patellar tendons (HPT) were mechanically tested to failure using atomic force microcopy (AFM). The effect of cross‐link stabilization by NaBH
4
in RTT was investigated. Continuity and structure of HPT fibrils was determined by electron microscopy serial sectioning (FIB‐SEM).
Results
Failure stress and high‐strain modulus were greater for the HPT (540±140 MPa, 4.3±1.4 GPa) than RTT fibrils (200±110 MPa, 1.4±0.7 GPa) (p<0.001) (see fig.). NaBH
4
had no effect on RTT fibril mechanics. In contras, fascicles showed higher failure stress (58±18 MPa vs 35±11 MPa, p=0.02) and reduced failure strain (5.0±0.8% vs 9.7±4.5%, p=0.05). A total of 1800 HPT fibrils were traced through 25μm deep FIB‐SEM stacks (total length = 45 mm), and only one fibril end, 4 fibril fusions and 3 fibril loops were observed.
Conclusion
Differences between RTT and HPT fibril properties are likely caused by greater cross‐link maturity in HPT, but seem unrelated to cross‐link lability since NaBH
4
had no effect on RTT fibrils. That reduction did have an effect at the fascicle level indicates the presence of reducible interfibrillar bonds. HPT fibril length data suggests that fibrils rarely end, but rather fuse to form a functionally continuous structure.
Aging negatively affects collagen-rich tissue like tendons, but in vivo tendon mechanical properties and the influence of physical activity after the 8
decade of life remains to be determined. This ...study aimed to compare in vivo patellar tendon mechanical properties in moderately old (OLD) and very old (VERY OLD) adults, and the effect of short term resistance training. Twenty OLD (9 women, 11 men, >65 y) and 30 VERY OLD (11 women, 19 men, >83 years) were randomly allocated to heavy resistance training (HRT) or no training (CON) and underwent testing of in vivo patellar tendon (PT) mechanical properties and PT dimensions before and after three months intervention. Previous measurements of muscle properties, blood parameters, and physical activity level were included in the analysis. Data from 9 OLD HRT, 10 OLD CON, 14 VERY OLD CON, and 12 OLD HRT were analyzed. In addition to lower quadriceps muscle strength and cross-sectional area (CSA), we found lower PT stiffness and Young's modulus (p<0.001) and a trend towards lower mid-portion PT-CSA (p=0.09) in VERY OLD compared to OLD. Daily step count was also lower in VERY OLD (p<0.001). Resistance training improved muscle strength and cross-sectional area equally in OLD and VERY OLD (p<0.05), but did not affect PT mechanical properties or dimension. We conclude that PT material properties are reduced in very old age, and this may likely be explained by reduced physical activity. Three months resistance training could, however, not alter PT mechanical properties in very old individuals.
Abstract only
Introduction
It remains unknown if life‐long habitual endurance exercise influences the accumulation of Advanced Glycation Endproducts (AGE) cross‐links that are closely associated with ...aging and disease in connective tissue.
Purpose
To examine the effect of aging and life‐long habitual endurance exercise on the collagen cross‐linking of the human patellar tendon.
Methods
We investigated 13 healthy injury free master athletes (old trained men, OT; age 59–75 years, running distance of 49±3 km/wk over 29±3 yrs (mean±SEM)), 12 old untrained controls (OC; matched to OT for BMI and age) and 10 young men matched for current running distance (young trained,YT; age 21–34, 48±4 km/week) and 12 young untrained controls (YC; matched to YT for BMI and age). Percutaneous tendon biopsies were obtained and analyzed for enzymatic (HP&LP) cross‐links, pentosidine, and collagen concent from the patellar tendon. A 2‐way ANOVA was used for statistical analysis.
Results
Pentosidine increased with age (P<0.001)(Pentosidine: OT, 39±4; OC, 48±3; YT, 11±2 and YC, 9±1 mmol/mol collagen). There was an interaction between age and training (P=0.019), such that master athletes (OT) had a lower tendon pentosidine than OC (P = 0.006).
Conclusion
These are the first data to demonstrate AGE cross‐links in tendon in male master athletes are lower compared to old untrained controls. The results suggest that life‐long habitual endurance exercise can counteract the aging process in tendon and thereby possibly reducing the risk of injury. Research support: Danish Association of Rheumatism.
tendon and skeletal muscle function adapts to physical training of resistive nature, but it is unknown to what extent persons with genetically altered connective tissue - who have a higher than ...normal tendon extensibility - will obtain any effect upon their tendon and muscle when undergoing muscle strength training. We investigated patients with classical Ehlers Danlos Syndrome (EDS) (collagen type V defect) who display articular hypermobility, skin extensibility and tissue fragility.
subjects underwent strength training 3 times a week for 4 months and were tested before and after intervention in regards to muscle strength, tendon mechanical properties, and muscle function.
three subjects completed the scheduled 48 sessions and had no major adverse events. Mean isometric leg extension force and leg extensor power both increased by 8 and 11% respectively (358 to 397 N, and 117 to 123 W). The tendon stiffness was tested and an average increase in response to physical training, from 1795 to 2519 N/mm was found. On average, the training loads both in upper and lower body exercises increased by around 30% over the training period. When testing balance, the average sway-area of the participants decreased by 26% (0.144 to 0.108 m(2)). On the subscale of CIS20 the participants lowered their average subjective fatigue score from 33 to 25.
in this small pilot study, heavy resistance training was both feasible and effective in classic Ehlers Danlos patients, and the results indicated that both tendon and skeletal muscle properties can be improved also in this patient group when they are subjected to resistance training.
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