Abstract：
The clearance of senescent cells may be detrimental to low cell density diseases, such as intervertebral disc degeneration (IVDD), and rejuvenating these cells presents a formidable obstacle. In this study, we investigate a mild-alkalization strategy employing magnesium boride-alginate (MB-ALG) hydrogels to rejuvenate senescent cells associated with age-related diseases. MB-ALG hydrogels proficiently ensnare senescent cells owing to their surface roughness. The hydrolysis of MB-ALG hydrogels liberates hydroxide ions (OH-), effecting a transition from an acidic microenvironment (pH ∼ 6.2) to a mildly alkaline state (pH ∼ 8.0), thereby fostering senescent cell proliferation via activation of the PI3K/Akt/mTOR pathway. Additionally, H2 aids in ROS clearance, which reduces cellular oxidative stress. And, Mg2+ rejuvenates senescent cells by inhibiting Ca2+ influx and fine-tuning the sirt1-p53 signaling pathways. Both in vitro and in vivo experiments conducted on rat intervertebral discs corroborate the sustained antisenescence and rejuvenation properties of MB-ALG hydrogels, with effects persisting for up to 12 weeks postoperation. These discoveries elucidate the role of mild-alkalization in dictating cellular destiny and provide key insights for addressing age-related diseases.
摘要：
清除衰老细胞可能对低细胞密度疾病有害，如椎间盘退变（IVDD），使这些细胞恢复活力是一个巨大的障碍。在这项研究中,我们研究了采用硼化镁-藻酸盐(MB-ALG)水凝胶的温和碱化策略,以恢复与年龄相关疾病相关的衰老细胞的活力.MB-ALG水凝胶由于其表面粗糙度而熟练地吸引衰老细胞。MB-ALG水凝胶的水解释放氢氧离子（OH-），实现从酸性微环境(pH~6.2)到轻度碱性状态(pH~8.0)的转变，从而通过激活PI3K/Akt/mTOR途径促进衰老细胞增殖。此外,H2有助于清除ROS，减少细胞氧化应激。And,Mg2+通过抑制Ca2+流入和微调sirt1-p53信号通路使衰老细胞恢复活力。在大鼠椎间盘上进行的体外和体内实验证实了MB-ALG水凝胶的持续抗衰老和恢复活力的特性，术后效果持续12周。这些发现阐明了轻度碱化在决定细胞命运中的作用，并为解决与年龄有关的疾病提供了关键见解。
