INTRODUCTION: TSC1mKO mice have muscle-specific knockout of the TSC1 inhibitor that leads to paraspinal myopathy-induced kyphosis and disc degeneration which is useful in the study of sarcopenia and the aging spine. Exercise has been commonly used for sarcopenia treatment, but its impact on spinal degeneration remains unclear. In this study, we examine general treadmill exercise on paraspinal muscle myopathy, intervertebral disc degeneration and kyphosis in female TSC1mKO mice.

METHODS: Twenty-five female mice were used for this study (TSC1mKO: n = 7, control: n = 7, TSC1mKO exercise (TSC1mKOEx): n=4, control exercise (ControlEx) n=7). Cobb angle, disc height was measured using high resolution microCT at 12 months. Exercise group mice were treated by uphill treadmill exercise 5 days/week between 8 and 12 months (2 stints of a 3-week exercise). At the end of treatment, time to exhaustion was measured. Myopathic changes in the paraspinal muscle were examined via Wheat Germ Agglutinin (WGA)/DAPI stain, and IVD was evaluated via FAST stain.

RESULTS: Similar to our previous study[1], TSC1mKO mice developed 1) accelerated myopathy representative of sarcopenia with histological sections showing presence of central nuclei and triangular fibres, 2) larger thoracolumbar kyphosis, and 3) faster intervertebral disc degeneration in terms of disc height loss and higher FAST staining disc scores at L3/4, L4/5 compared to controls.

After uphill treadmill exercise regime, the endurance performance of TSC1mKO exercise mice reached a level comparable to control sedentary mice level (>1000s) while TSC1mKO mice had reduced endurance of 750s. Exercise reduced the proportion of triangular degenerated fiber (TSC1mKOEx 2.9±0.1% vs TSC1mKO 6.3±4.8%, p= 0.07) in TSC1mKO mice. (Figure 1A)

In terms of disc health, exercise improved disc heights of control mice at L4/5 (ControlEx 294 ±33µm vs Control 247 ± 59µm, p=0.03) but not in TSC1mKO mice (TSC1mKOEx 164±42µm vs TSC1mKO 164 ±27µm, p=0.49), as well as the disc scores of control mice at L4/5 (ControlEx 1.25 ±0.50 vs control 2.0 ±0.53, p=0.025) but not in TSC1mKO mice (TSC1mKO 5.38 ±1.69 vs TSC1mKOEx 6.50±1.91, p= 0.18) (Figure 1B). Interestingly, exercise increased disc matrix/disc tissue area at L4/5 in TSC1mKO mice (TSC1mKOEx 59.4±17.3% vs TSC1mKO 37.4±13.1%, p=0.04) but not in control mice (ControlEx 61.9±19.3% vs Control 47.3±1.3%, p=0.14). (Figure 1C)

In spite of exercise, there were no changes in spinal kyphosis for both TSC1mKO mice (TSC1mKOEx 82.17±14.87° vs TSC1mKO 83.67±17.18°, p=0.44) (Figure 1D) and control mice (ControlEx 47.8±15.5° vs control 57.1±16.7°, p=0.17).

DISCUSSION: This study demonstrated that general treadmill exercise can improve overall TSC1mKO mice endurance and paraspinal myopathy. It fails to improve intervertebral disc health but increases disc matrix formation in TSC1mKO mice compared to control mice. Exercise has no impact on spinal alignment for all mice. This study supports further optimization of exercise regimes to be paraspinal muscle-specific, so as to treat the spinal degenerative process.