Klotho senolytic reduces ECM degradation and neo-angiogenesis in IDD through inhibition of the Ras-1/PAK-1/MMP-2 signaling axis (by inhibition of Ras-associated substrate botulinum toxin C3 1 (Ras-1)/PAK-1 and MMP-2 protein expression by exogenous co-administration with Klotho with Ras-1 inhibitor) [99]. Here, PAK1 is linked to intervertebral disk degenerative disorder.