Ten weeks of treadmill running decreases stiffness and increases collagen turnover in tendons of old mice

Abstract

Increased tendon stiffness in response to mechanical loading is well established in young animals. Given that tendons stiffen with aging, we aimed to determine the effect of increased loading on tendons of old animals. We subjected 28-month-old mice to 10 weeks of uphill treadmill running; sedentary 8-and 28-month-old mice served as controls. Following training, plantaris tendon stiffness and modulus were reduced by approximately half, such that the values were not different from those of tendons from adult sedentary animals. The decrease in plantaris tendon stiffness was accompanied by a similar reduction in the levels of advanced glycation end-product protein adducts in tibialis anterior tendons of trained compared with sedentary old mice. In Achilles tendons, elevated mRNA levels for collagen type 1, matrix-metalloproteinase-8, and lysyl oxidase following training suggest that collagen turnover was likely also increased. The dramatic mechanical and structural changes induced by training occurred independent of changes in cell density or tendon morphology. Finally, Achilles tendon calcification was significantly reduced following exercise. These results demonstrate that, in response to exercise, tendons from old animals are capable of replacing damaged and dysfunctional components of extracellular matrix with tissue that is mechanically and structurally comparable to adult tissue. ß

Mechanobiology of young and aging tendons: In vivo studies with treadmill running

“…Calcification, which is minimal in adult tendons, increases significantly with age. However, mechanical loading significantly reduces Achilles tendon calcification in old mice following exercise . The findings of this study indicate that age‐related changes in tendon can be modified with mechanical loading; they also reaffirm that even tendons from old animals are capable of replacing damaged and dysfunctional components of ECM to match with that of adult.…”

“…In addition, MTR significantly increases the expression of stem cell markers, tenocyte genes, and down regulates non‐tenocyte related genes. A recent study subjected 28‐month‐old mice to 10 weeks of MTR (13 m/min, 6° incline, 30 min/day, 5 days/week); sedentary 8‐ and 28‐month‐old mice served as controls . The gene expression analysis from Achilles tendons of trained aging rats shows that Col1a1 and MMP8, which were decreased due to aging are restored to the same levels as that of adult mice after training.…”

“…A recent study subjected 28-month-old mice to 10 weeks of MTR (13 m/min, 6˚incline, 30 min/day, 5 days/week); sedentary 8-and 28-monthold mice served as controls. 43 The gene expression analysis from Achilles tendons of trained aging rats shows that Col1a1 and MMP8, which were decreased 562 THAMPATTY AND WANG due to aging are restored to the same levels as that of adult mice after training. Advanced glycation endproducts (AGEs) adduct concentration increases 60% with aging in tibialis tendons whereas treadmill running decreases AGE adducts to a value similar to adult controls.…”

Evaluation of tissue displacement and regional strain in the Achilles tendon using quantitative high-frequency ultrasound

“…It has also been shown that changes at the interfascicular matrix is an important factor to consider in the pathogenesis of tendinopathy [36]. With respect to pathogenesis and the effects of ageing and loading, other research has shown that ageing leads to changes in the tendon morphology and mechanics [37] with increase in non-enzymatic crosslinks and as a consequence an expected increase in stiffness [38]. However, stiffness seems to decrease as we age [39].…”

Effects of aging and resistance training in rat tendon remodeling

“…In addition, mechanical loading can regulate the expression of several growth factors capable of stimulating collagen synthesis, such as TGF-b1, CTGF, and IGF-1 (31), which, in turn, increases type I and III collagen synthesis in peritendinous connective tissue in both human and rat tendons (14,32). In response to exercise, the tendons of old animals are capable of replacing damaged and dysfunctional components of ECM with tissue that is mechanically and structurally comparable to adult tissue (33). However, after treadmill running, the amount of lipid deposits decreased, and small amounts of proteoglycans and calcium sites remained in the patellar tendons of mice (23).…”