[Age-related dynamics of the contents of matrix metalloproteinases (MMP-1, -2, -3, -9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, -2, -4) in blood plasma of residents of the European part of the Arctic zone of the Russian Federation.]

Here we present the study of enzymes involved in the regulation of extracellular matrix metabolism. It was the first study of this kind in the European part of the Arctic zone of the Russian Federation (AZRF). The contents of matrix metalloproteinases (MMP-1, -2, -3, -9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, -2, -4) were measured in blood plasma of 91 men in AZRF (67o N) and 14 men in Western Siberia. The contents of MMP-1, MMP-9, TIMP-1 and TIMP-4 in plasma of northerners were higher compared to those of the residents of Western Siberia (55o N). Age-related dynamics of MMP and TIMP contents had a mixed trend in northerners. The maximum contents of MMP-1 and MMP-9 and of MMP-3 were observed in 30-39 and 40-49 years old groups, respectively. The contents of these enzymes tended to decease with age. The maximum contents of TIMP-1 and TIMP-2 and of TIMP-4 were in 50-59 and 60-69 years old groups, respectively, while the minimum contents of these enzymes were in the group of young men up to 29 years old. Hyaluronidase activity was minimal in 30-39 years old group and increased with age up to maximum values at 50-59 years old. Age-related imbalance of MMP/TIMP system (MSE content reduction with age vs TIMP content increase in older age groups) can be considered one of the reasons of the identified age-related increase of interstitial fibrosis and premature aging of the northerners.

[Melatonin and man aging in the European part of the Arctic zone of the Russian Federation.]

The analysis of 6-sulfatoxymelatonin (6-SMT) levels in working-age men (aged 19-69) who live in the European part of the Arctic zone of the Russian Federation is presented. Their urine 6-SMT levels were similar to those of comparison group (residents of Western Siberia). The level of 6-SMT decreased with age and was the lowest in 40-49-year group. Age group 60-69 tended to demonstrate increasing 6-SMT levels. Thus, they were insignificantly different (p>0,05) compared to those of people under 29. We showed that alcohol influenced 6-SMT level. The level was lower in alcohol-consuming north men compared to non-consumers. Free testosterone level in plasma of northerners decreased with age. In 60-69-year group, the level was 50% of that in under-29-year group. Compared to controls, we observed the activation of lipid peroxidation that was not compensated by increased activity of glutathione reductase and plasma SH groups. Age-related decrease in the melatonin metabolite, as an endogenous antioxidant, was accompanied by a gradual accumulation of lipid peroxidation products and lower antioxidative protection mediated by SH groups.

[Age-related dynamics of the main extracellular matrix components in residents of the Russian Arctic].

The main extracellular matrix components in Arctic residents were studied. Northerners had increased levels of total glycosaminoglycans, hyaluronan, and collagen IV in plasma and both general and peptide-bound hydroxyproline in urine, which indicates an accelerated metabolism of the main extracellular matrix components compared with comparison group (residents of Siberia). Age-related remodeling of extracellular matrix in northerners manifested in changing ratio and quantity of its main components. Levels of total glycosaminoglycans, hyaluronan, fibronectin, hydroxyproline and its fractions increased with age while the level of collagen IV changed insignificantly. Average positive correlation between extracellular matrix components and biological aging indicators is suggestive of relationship between these two processes: aging - which is accelerated in the Arctic and pathological remodeling of extracellular matrix as it is associated with accelerated aging. Changes in local regulation system including those related to matrix metalloproteinases and their tissue inhibitors may be one of the reasons for pathological remodeling of extracellular matrix.