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Effects of lifelong physical activity on tendon function have been investigated in cross-sectional studies, but these are at risk of "survivorship" bias. Here, we investigate whether lifelong side-specific loading is associated with greater cross-sectional area (CSA), mechanical properties, cell density (DNA content), and collagen cross-link composition of the male human patellar tendon (PT), in vivo. Nine seniors and six young male lifelong elite badminton players and fencers were included. CSA of the PT obtained by 3-tesla MRI and ultrasonography-based bilateral PT mechanics were assessed. Collagen fibril characteristics, enzymatic cross links, nonenzymatic glycation (autofluorescence), collagen, and DNA content were measured biochemically in PT biopsies. The elite athletes had a ≥15% side-to-side difference in maximal knee extensor strength, reflecting chronic unilateral sport-specific loading patterns. The PT CSA was greater on the lead extremity compared with the nonlead extremity (17%, P = 0.0001). Furthermore, greater tendon stiffness (18%, P = 0.0404) together with lower tendon stress (22%, P = 0.0005) and tendon strain (18%, P = 0.0433) were observed on the lead extremity. No effects were demonstrated from side-to-side for glycation, enzymatic cross link, collagen, and DNA content (50%, P = 0.1160). Moreover, tendon fibril density was 87 ± 28 fibrils/μm 2 on the lead extremity and 68 ± 26 fibrils/μm 2 on the nonlead extremity (28%, P = 0.0544). Tendon fibril diameter was 86 ± 14 nm on the lead extremity and 94 ± 14 nm on the nonlead extremity (-9%, P = 0.1076). These novel data suggest that lifelong side-specific loading in males yields greater patellar tendon size and stiffness possibly with concomitant greater fibril density but without changes of collagen cross-link composition. NEW & NOTEWORTHY The present data demonstrate that lifelong side-specific loading yields greater patellar tendon structure on the lead extremity without affecting glycation that is associated with aging. These novel data suggest that lifelong side-specific habitual loading induce structural alterations that may serve to improve the mechanical properties of the tendon.

Tendon pathology (tendinopathy) typically occurs in specific regions of a tendon, and growth in response to exercise also appears to be more pronounced in specific regions. In a previous study in animals we found evidence of regional differences in tendon turnover, but whether the turnover of human patellar tendon differs in different regions still remains unknown. Patellar tendons were obtained from cadavers of healthy men and women (body donation program, n = 5 donors, >60 yr of age). Samples were taken from 10 different regions along the length, width, and thickness of the tendon. Turnover was measured by 14 C bomb pulse dating and also estimated from the accumulation of advanced glycation end products (AGEs) by fluorescence (340/460 nm) in addition to measurement of specific AGEs by mass spectrometry. Composition in terms of collagen, glycosaminoglycans (GAGs), and DNA was also assessed in each region. 14 C results showed that all tendon regions had a similar 14 C concentration, which was equal to the average atmospheric 14 C concentration during the first 15 yr of the person's life. Fluorescence normalized to dry weight did not differ between regions, nor did specific AGEs. Higher GAG content was observed in the proximal and near the distal insertion of the tendon. In conclusion, healthy human patellar tendon displays no regional differences in collagen turnover throughout life. NEW & NOTEWORTHY Tendon injuries and tendinopathies typically occur in specific regions of the tendon, but the reason for this specificity is not well understood. A potential factor in injury susceptibility is tissue turnover, and previous work suggests that the tendon core has practically no turnover during adult life; however, it is not known whether this is true for other regions of the tendon. Our present results on healthy human patellar tendon clearly demonstrate that turnover does not differ between regions and thereby cannot explain differences in injury susceptibility. The findings also indicate that all regions of the tendon are formed simultaneously during skeletal maturation and do not turn over appreciably during adulthood. This is an important finding because little is known about tendon growth during maturation in humans.

Aging negatively affects collagen-rich tissue, like tendons, but in vivo tendon mechanical properties and the influence of physical activity after the 8th decade of life remain to be determined. This study aimed to compare in vivo patellar tendon mechanical properties in moderately old (old) and very old adults and the effect of short-term resistance training. Twenty old (9 women, 11 men, >65 yr) and 30 very old (11 women, 19 men, >83 yr) adults 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 a 3-mo 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 adults 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 toward the lower mid-portion PT-CSA ( P = 0.09) in very old compared with old subjects. Daily step count was also lower in very old subjects ( P < 0.001). Resistance training improved muscle strength and cross-sectional area equally in old and very old subjects ( 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 of resistance training however, could not alter PT mechanical properties in very old individuals. NEW & NOTEWORTHY This research is the first to quantify in vivo tendon mechanical properties in a group of very old adults in their eighties. Patellar tendon stiffness was lower in very old (87 yr on average) compared with moderately old (68 yr on average) individuals. Reduced physical activity with aging may explain some of the loss in tendon stiffness, but regular heavy resistance training for 3 mo was not sufficient to change tendon mechanical properties.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used as pain killers during periods of unloading caused by traumatic occurrences or diseases. However, it is unknown how tendon protein turnover and mechanical properties respond to unloading and subsequent reloading in elderly humans, and whether NSAID treatment would affect the tendon adaptations during such periods. Thus we studied human patellar tendon protein synthesis and mechanical properties during immobilization and subsequent rehabilitating resistance training and the influence of NSAIDs upon these parameters. Nineteen men (range 60-80 yr) were randomly assigned to NSAIDs (ibuprofen 1,200 mg/day; Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2 wk and retrained for 6 wk. Tendon collagen protein synthesis, mechanical properties, size, expression of genes related to collagen turnover and remodeling, and signal intensity (from magnetic resonance imaging) were investigated. Tendon collagen synthesis decreased (P < 0.001), whereas tendon mechanical properties and size were generally unchanged with immobilization, and NSAIDs did not influence this. Matrix metalloproteinase-2 mRNA tended to increase (P < 0.1) after immobilization in both groups, whereas scleraxis mRNA decreased with inactivity in the Plc group only (P < 0.05). In elderly human tendons, collagen protein synthesis decreased after 2 wk of immobilization, whereas tendon stiffness and modulus were only marginally reduced, and NSAIDs had no influence upon this. This indicates an importance of mechanical loading for maintenance of tendon collagen turnover. However, reduced collagen production induced by short-term unloading may only marginally affect tendon mechanical properties in elderly individuals., New & Noteworthy: In elderly humans, 2 wk of inactivity reduces tendon collagen protein synthesis, while tendon stiffness and modulus are only marginally reduced, and NSAID treatment does not affect this. This indicates that mechanical loading is important for maintenance of tendon collagen turnover and that changes in collagen turnover induced by short-term immobilization may only have minor impact on the internal structures that are essential for mechanical properties in elderly tendons., (Copyright © 2017 the American Physiological Society.)

Here, we review the literature on how tendons respond and adapt to ageing and exercise. With respect to aging, there are considerable changes early in life, but this seems to be maturation rather than aging per se. In vitro data indicate that aging is associated with a decreased potential for cell proliferation and a reduction in the number of stem/progenitor-like cells. Further, there is persuasive evidence that turnover in the core of the tendon after maturity is very slow or absent. Tendon fibril diameter, collagen content, and whole tendon size appear to be largely unchanged with aging, while glycation-derived cross-links increase substantially. Mechanically, aging appears to be associated with a reduction in modulus and strength. With respect to exercise, tendon cells respond by producing growth factors, and there is some support for a loading-induced increase in tendon collagen synthesis in humans, which likely reflects synthesis at the very periphery of the tendon rather than the core. Average collagen fibril diameter is largely unaffected by exercise, while there can be some hypertrophy of the whole tendon. In addition, it seems that resistance training can yield increased stiffness and modulus of the tendon and may reduce the amount of glycation. Exercise thereby tends to counteract the effects of aging., (Copyright © 2016 the American Physiological Society.)

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., (Copyright © 2016 the American Physiological Society.)