A great many research groups are engaged in the search for distinct biochemistry in extremely old humans. How do older individuals survive where their peers did not, and can any of the answer to that question be turned into useful therapies? My suspicion is that there are no useful therapies to be found in the genetics and metabolism of exceptional human longevity: these people are still suffering a high burden of damage, and are greatly diminished in capacity. The differences they carry do not tend to swing the odds far, and epidemiological studies suggest that individual variation in genetics and metabolism is a tiny contribution compared to life-long lifestyle choices.

The matrix metalloproteinase (MMP) group of proteins controls a large variety of key physiological and pathological processes, including tissue remodelling, DNA replication, cell-cycle progression, neurodegeneration, and cancer. MMP-2 is constitutively expressed in several tissues and is tightly associated with inflammatory states such as osteoarthritis. MMP-9 is implicated in lipid metabolism and its activity contributes to endothelial dysfunction.

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.

Link: https://doi.org/10.1155/2020/8635158