Achilles tendon mechanosensitivity is preserved in old age: In vivo evidence from a 1.5 years long resistance training intervention

Introduction Ageing deteriorates musculoskeletal system structure and function and limits its adaptability to mechanical loading. Medium-term (12-14 weeks) exercise interventions in older adults have been shown to increase tendon stiffness by increasing the tendon’s Young’s modulus [1], rather than the tendon’s cross-sectional area (CSA). However, little is known about the time-adaptive response relationship of the tendon in long-term (years) interventions involving alteration in mechanical loading. Therefore, we investigated whether the older human Achilles tendon (AT) demonstrates mechanosensitivity and alterations in material and/or size in response to long-term mechanical loading. Methods Thirty-four older female adults (age: 65±7 y) were recruited to a medium-term (14 weeks; n=21) strength training intervention with high AT strain cyclic loading (five sets of four repetitions of isometric plantarflexion contractions 3 times a week with 90% of MVC as in [2]) or a control group (n=13), with a sub-group of the intervention group (n=12) continuing exercise for 1.5 years. AT stiffness and Young’s modulus were quantified in vivo using ultrasonography and dynamometry. Tendon CSA was measured along the whole free AT by means of magnetic resonance imaging. Results Following 14 weeks of resistance training, the intervention group showed a significant (p<.05) increase in ankle plantarflexor muscle strength (141.5±36.2 vs 116.3±30.8 Nm at baseline), along with a 23% increase in AT stiffness (598.2±141.2 Nmm-1 vs 488.4±136.9 Nmm-1 at baseline), 20% increase in Young’s modulus (1.63±0.46 GPa vs 1.37±0.39 GPa at baseline) and a homogenous hypertrophy by about 6% along the entire free AT. However, continuing the exercise training for 1.5 years did not cause any further changes in muscle strength and tendon properties. The control group did not show any differences in muscle and tendon functional and structural properties between time points. Discussion The AT seems to have the capability to increase its stiffness in response to 14 weeks of mechanical loading exercise by altering both its material and size, and may thereby tolerate higher mechanical loading by reducing both the strain and stress it experiences during tensile loading. Continuing strength training appears to maintain, but not cause any further adaptive changes in tendons, which implies that the time-adaptive response relationship to mechanical loading is non-linear in ageing tendons. References 1. Reeves et al. (2003). J Physiol, 548, 971–981. 2. Arampatzis et al. (2007). J Exp Biol, 210, 2743–2753

VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy

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Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status

Background: Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer’s continuum in the 2018 NIA-AA research framework. Objective: This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus. Methods: From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ−) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB). Results: ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAβ+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAβ+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAβ+) and precuneus SUVRFBB (both groups). Conclusion: While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAβ+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-β load, highlighting incipient pathology in stage 2 of the AD continuum

Vascular Wall-Resident CD44+ Multipotent Stem Cells Give Rise to Pericytes and Smooth Muscle Cells and Contribute to New Vessel Maturation

Here, we identify CD44(+)CD90(+)CD73(+)CD34(−)CD45(−) cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs). VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFß1 stimulation up-regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes

The role of muscle strength on tendon adaptability in old age.

PURPOSE: The purpose of the study was to determine: (1) the relationship between ankle plantarflexor muscle strength and Achilles tendon (AT) biomechanical properties in older female adults, and (2) whether muscle strength asymmetries between the individually dominant and non-dominant legs in the above subject group were accompanied by inter-limb AT size differences. METHODS: The maximal generated AT force, AT stiffness, AT Young's modulus, and AT cross-sectional area (CSA) along its length were determined for both legs in 30 women (65 ± 7 years) using dynamometry, ultrasonography, and magnetic resonance imaging. RESULTS: No between-leg differences in triceps surae muscle strength were identified between dominant (2798 ± 566 N) and non-dominant limb (2667 ± 512 N). The AT CSA increased gradually in the proximo-distal direction, with no differences between the legs. There was a significant correlation (P < 0.05) of maximal AT force with AT stiffness (r = 0.500) and Young's modulus (r = 0.414), but only a tendency with the mean AT CSA. However, region-specific analysis revealed a significant relationship between maximal AT force and the proximal part of the AT, indicating that this region is more likely to display morphological adaptations following an increase in muscle strength in older adults. CONCLUSIONS: These findings demonstrate that maximal force-generation capabilities play a more important role in the variation of AT stiffness and material properties than in tendon CSA, suggesting that exercise-induced increases in muscle strength in older adults may lead to changes in tendon stiffness foremost due to alterations in material rather than in its size