Zinc-bound metallothioneins as potential biological markers of ageing

Metallothioneins (MTs) (I+II) play pivotal roles in metal-related cell home ostasis because of their high affinity for metals forming clusters. The mai n functional role of MTs is to sequester and/or dispense zinc participating in zinc homeostasis. Consistent with this role, MT gene expression is tras criptionally induced by a variety of stressing agents to protect cells from reactive oxygen species. In order to accomplish this task, MTs induce the secretion of pro-inflammatory cytokines by immune and brain cells, such as astrocytes, for a prompt response against oxidative stress. These cytokines are in turn involved in new synthesis of MTs in the liver and brain. Such protective mechanism occurs in the young-adult age, when stresses are trans ient. Stress-like condition is instead constant in the old age, and this ca uses continuous stealing of intracellular zinc by MTs and consequent low bi oavailability of zinc ions for immune, endocrine, and cerebral functions. T herefore, a protective role of zinc-bound MTs (I+II) during ageing can be q uestioned. Because free zinc ions are required for optimal efficiency of th e immune-endocrine-nervous network, zinc-bound MTs (I+II) may play a differ ent role during ageing, switching from a protective to a deleterious one in immune, endocrine, and cerebral activities. Physiological zinc supply, per formed cautiously, can correct deficiencies in the immune-neuroendocrine ne twork and can improve cognitive performances during ageing and accelerated ageing. Altogether these data indicate that zinc-bound MTs (I+II) can be co nsidered as novel potential markers of ageing. (C) 2001 Elsevier Science In c.