Department of Biological Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.
Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy.
Mediators Inflamm. 2020 May 5;2020:8635158. doi: 10.1155/2020/8635158. eCollection 2020.
Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant haematochemical parameters in a Sicilian population, including long-living individuals (LLIs, ≥95 years old). A cohort of 154 healthy subjects (72 men and 82 women) of different ages (age range 20-112) was recruited. The cohort was divided into five subgroups: the first group with subjects less than 40 years old, the second group ranging from 40 to 64 years old, the third group ranging from 65 to 89 years old, the fourth group ranging from 90 to 94 years old, and the fifth group with subjects more than 95 years old. A relationship was observed between LLIs and MMP-2, but not between LLIs and MMP-9. However, in the LLI group, MMP-2 and MMP-9 values were significantly correlated. Furthermore, in LLIs, we found a positive correlation of MMP-2 with the antioxidant catabolite uric acid and a negative correlation with the inflammatory marker C-reactive protein. Finally, in LLIs MMP-9 values correlated directly both with cholesterol and with low-density lipoproteins. On the whole, our data suggest that the observed increase of MMP-2 in LLIs might play a positive role in the attainment of longevity. This is the first study that shows that serum activity of MMP-2 is increased in LLIs as compared to younger subjects. As far as we are concerned, it is difficult to make wide-ranging conclusions/assumptions based on these observations in view of the relatively small sample size of LLIs. However, this is an important starting point. Larger-scale future studies will be required to clarify these findings including the link with other systemic inflammatory and antioxidant markers.
细胞外基质金属蛋白酶（MMPs）是一组通过酶切激活底物的蛋白质，根据其活性，已被证明在衰老中发挥作用。因此，为了深入了解衰老的病理生理学并确定长寿的新标志物，我们分析了西西里人群中 MMP-2 和 MMP-9 的活性水平与一些相关的血液化学参数之间的关系，其中包括长寿个体（LLI，≥95 岁）。我们招募了一组不同年龄（年龄范围为 20-112 岁）的 154 名健康受试者（72 名男性和 82 名女性）。该队列被分为五个亚组：第一组年龄小于 40 岁，第二组年龄在 40-64 岁之间，第三组年龄在 65-89 岁之间，第四组年龄在 90-94 岁之间，第五组年龄大于 95 岁。我们观察到 LLI 与 MMP-2 之间存在关系，但 LLI 与 MMP-9 之间不存在关系。然而，在 LLI 组中，MMP-2 和 MMP-9 的值显著相关。此外，在 LLI 中，我们发现 MMP-2 与抗氧化剂代谢产物尿酸呈正相关，与炎症标志物 C 反应蛋白呈负相关。最后，在 LLI 中，MMP-9 值与胆固醇和低密度脂蛋白均呈直接相关。总的来说，我们的数据表明，在 LLI 中观察到的 MMP-2 增加可能在达到长寿方面发挥积极作用。这是第一项表明 MMP-2 血清活性在 LLI 中比年轻个体增加的研究。就我们而言，鉴于 LLI 的样本量相对较小，很难根据这些观察结果得出广泛的结论/假设。然而，这是一个重要的起点。需要进行更大规模的未来研究来阐明这些发现，包括与其他系统性炎症和抗氧化标志物的联系。
