Polyamines in mammalian ageing: An oncological problem, too? A review

Abstract

This review surveys the literature about changes in polyamine contents and levels of activity of the enzymes involved in the polyamine biosynthetic pathway in organs of ageing mammals. The literature about changes in the polyamine levels in physiological fluids in healthy ageing humans is also reviewed. Generally speaking, decreases in the levels of the main polyamines (noticeably putrescine and spermidine) are observed in different mammalian organs with ageing. The polyamine levels in serum and in urine of healthy human beings are also age-related, declining progressively with increasing age. Some major enzymes (i.e., ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50)) involved in the polyamine biosynthetic pathway show similar trends. Hormonal induction of ornithine decarboxylase activity is strongly reduced in organs of aged animals, as it is in neoplastic organs. There is also some evidence for an age-related decrease in the level of ornithine decarboxylase and its inducibility in mammalian cells cultured in vitro. Some in vitro effects of spermidine and spermine on aged structures or systems are briefly summarized. There is no evidence yet that this generally reduced capacity of mammalian aged organs for polyamine biosynthesis is one of the factors responsible for the well known high incidence of some neoplasias in elderly humans. In view of the typical stimulatory effects of the tumour promoters on polyamine biosynthesis in target tissues and the effects of senescence on the same metabolic pathway, it can be excluded that the ageing process has a tumour promoting effect by itself. However, although the exact mechanism responsible for the increased occurrence of some tumors during mammalian senescence is still obscure, there are enough experimental data (both in humans and in animals) to indicate that the reduced polyamine biosynthetic capacity of aged mammals can account for the slower course of some tumors in elderly patients.