Age-dependent changes in glycosaminoglycan content in the skin of fasted rats. A possible mechanism.

It is well recognized that during fasting or aging of animals there is a decreased content of several extracellular matrix components in the skin, including glycosaminoglycans (GAGs) and decrease in biosynthesis of these macromolecules. The mechanism for the phenomena is not known. We considered skin and blood lactate as a potential candidate to control GAG metabolism in tissues. Energetic metabolism, reflected by NAD/NADH and lactate/pyruvate ratios is changed during aging or fasting and lactate inhibits at least some GAGs biosynthesis. Therefore we have compared the level of lactate and the ratios of lactate to pyruvate in the blood and skin of fasted young and fasted adult rats and correlated them with the content of skin glycosaminoglycans. It has been found that the skin of adult rats contains about 60% of GAGs found in the skin of young animals. Fasting of both groups of animals resulted in further decrease in skin GAG content. GAG content in the skin of fasted young animals was decreased by 30% while in fasted adult rats no significant differences were observed, compared to fed animals. Lactate concentration was found to be increased over 2-fold in the skin of young fasted rats, compared to young controls. The lactate concentration in adult animals was not changed during fasting, although in both cases the lactate levels were almost 3-fold higher than in young control rats. In blood, lactate concentration increased by 40% during fasting of young animals while it decreased by about 40% during fasting of adult rats. Although no differences were found in blood lactate level between young and adult rats, the ratio of lactate/pyruvate was decreased by over 2 fold in adult rats. The relative differences in mean GAG content in the skin of all experimental groups of animals were related to the similar differences in blood glucose and lactate/pyruvate ratio. Therefore not only skin lactate but also blood lactate concentrations may reflect the extent of skin GAG biosynthesis. We have noticed that increase in the ratio of skin lactate/pyruvate concentration and decrease of the ratio in the blood is accompanied by decrease in the skin GAG content. We suggest that the phenomenon may result from utilization of lactate into glucose in the Cori cycle which regulate glucose availability for GAG biosynthesis. Therefore it can be suggested that lactate may participate in inhibition of skin GAG biosynthesis and the extent of the inhibition is reflected by the ratio of lactate/pyruvate concentrations both in the skin and blood.