The relevance of proteins involved in zinc homeostasis has been
particularly studied since the discovery of the zinc binding proteins
called metallothioneins (MT). Despite the great interest aroused around
these proteins, an unequivocally established biological function for MT
has not yet been defined. What is firm is that MT bound zinc with high
affinity but, at the same time, release free Zn ions in response to
oxidative stress, suggesting an intriguing role for zinc, similar to
that found for calcium as signal transducer. In other words zinc
signals tells the cells to express "shield" and "protection" genes such
as chaperones and MT and trigger the activation of intracellular
"weapons", such as the CuZn-superoxide dismutase (SOD) enzyme, to fight
oxidative stress. For instance, zinc deficiency prejudices immune
functions, impairs cognitive performance and brain functions. Moreover,
zinc deficiency is a common event in aging due to a reduced intake of
this trace element and perhaps to the persistent stress induced
overexpression of zinc-binding proteins such as MT. In contrast, zinc
excess causes also detrimental effects probably due to the binding of
zinc to metalloproteins that require other metals for their biological
activities and to a massive activation of some zinc dependent enzymes,
which, in turn, depletes intracellular energy stores. The influx of
toxic amounts of zinc into degenerating neurons seems to be mainly
responsible for the neurodegenerative process in transient forebrain
ischemia, seizures and traumatic brain injury, and excessive amount of
zinc may have a role in Alzheimer pathology. Therefore, it is not
surprising that the cell uses sophisticated mechanisms to control the
intracellular levels and movements of zinc. The age-related alteration
of these mechanisms have been just begun to be studied and constitute a
growing field of research in order to search for anti-aging targets.
However, before developing these therapies it is necessary to better
clarify the biology and biochemical features of these mechanisms with
particular attention to aging, taking also carefully into account that
what is of benefits during young/adult age may be detrimental in aging.
New insight into the functionality of zinc homeostasis in aging may be
acquired soon, with the application in aging research of specific
fluorescent "zinc sensors", which localize into different intracellular
compartments and stain specifically the amount of free plus "loosely
bound" zinc.
Key words:
zinc, zinc homeostasis, aging, metallothioneins
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