Ageing does not result in a decline in cell synthetic activity in an injury prone tendon

Abstract

1Advancing age is a well-known risk factor for tendon disease. Energy storing tendons, (e.g. 2human Achilles, equine superficial digital flexor tendon (SDFT)) are particularly vulnerable 3 and it is thought that injury occurs following an accumulation of micro-damage in the 4 extracellular matrix (ECM). Several authors suggest that age-related micro-damage 5 accumulates due to a failure of the aging cell population to maintain the ECM or an 6 imbalance between anabolic and catabolic pathways. We hypothesised that ageing results in a 7 decreased ability of tendon cells to synthesise matrix components and matrix degrading 8 enzymes, resulting in a reduced turnover of the ECM and a decreased ability to repair micro-9 damage. The SDFT was collected from horses aged 3-30 years with no signs of tendon 10 injury. Cell synthetic and degradative ability was assessed at the mRNA and protein levels. 11Telomere length was measured as an additional marker of cell ageing. There was no decrease 12 in cellularity or relative telomere length with increasing age, and no decline in mRNA or 13 protein levels for matrix proteins or degradative enzymes. The results suggest that the 14 mechanism for age-related tendon deterioration is not due to reduced cellularity or a loss of 15 synthetic functionality and that alternative mechanisms should be considered.

Aging does not alter tendon mechanical properties during homeostasis, but does impair flexor tendon healing

“…Our secondary focus was investigating the effects of aging on FDL tendon healing. Consistent with healing in other tendons, our data demonstrate that aging impairs restoration of mechanical properties and results in decreased matrix deposition …”

Age‐related changes of tendon fibril micro‐morphology and gene expression

“…The findings by Thorpe et al () and our study also support the assumption that whereas energy‐storing tendons appear to be able to respond to the mechanical forces during growth, there is no evidence that they can do so after skeletal maturity. Instead, cumulative fatigue damage may cause degeneration, potentially weakening tendons and increasing the risk of tendon injury (Smith et al, ).…”

“…In this study, the most striking differences for all analyzed parameters (fibril diameters and fibril counts, fibril diameter distributions and gene expression of tendon relevant genes) were found between immature (≤ 6 months) and mature tendons (≥ 2.75 years). This result may be considered complementary to Thorpe et al () who showed in their study that aging does not result in a decline in cell synthetic activity after the age of 3 years.…”

“…Additional analyses of the age‐specific protein synthesis, rather than changes of the intrinsic cellular function based merely on gene expression, may offer valuable information about the molecular biology dictating tendon development, maturation and aging. This was also suggested by Thorpe et al () who found that an important mechanism for age‐related tendon deterioration might be connected with protein post‐translational modifications.…”

Collagen V haploinsufficiency in a murine model of classic Ehlers–Danlos syndrome is associated with deficient structural and mechanical healing in tendons

“…This suggests that differences in healing properties are not caused by disparities in the recruitment of or number of tendon cells within the healing midsubstance. A rounded nuclear shape has been regarded as a sign of metabolic activation in response to matrix damage . Our findings suggest that reduction in collagen V and the resulting alterations in collagen I fibril structure do not impact this general response mechanism.…”