The immuno-reconstituting effect of melatonin or pineal
grafting and its relation to zinc pool in aging mice.
Mocchegiani E, Bulian D, Santarelli L, Tibaldi A, Muzzioli M, Pierpaoli W,
Fabris N.
Gerontology Research Department, Italian National Institute for Research on
Aging (INRCA), Ancona.
It has been demonstrated that melatonin, the main neuro-hormone of the pineal
gland, affects thymic functions and the regulation of the immune system. In
addition, experimental evidences indicate that melatonin can modulate zinc
turnover. The knowledge that with advancing age both melatonin and zinc plasma
levels decline, and that zinc supplementation in old mice is able to restore
the reduced immunological functions, has prompted investigations on the effect
of chronic melatonin treatment or pineal graft in old mice on the age-related
decline of thymic endocrine activity, peripheral immune functions and zinc
turnover. Both melatonin treatment in old mice and pineal graft into the
thymus of old mice correct the reduced thymic endocrine activity and increase
the weight of the thymus and its cellularity. A restoration of cortical thymic
volume, as detected by the percentage of tissue in active proliferation, is
also observed in old mice after both treatments. Thymocyte CD phenotype
expression is also restored to young values. At peripheral level, recovery of
peripheral blood lymphocyte number and of spleen cell subsets, with increased
mitogen responsiveness also occurs. Melatonin treatment or pineal graft induce
also a restoration of the altered zinc turnover in aged mice with an increment
of the crude zinc balance from negative (-1.6 microgram/day/mouse) to positive
value (+1.2 microgram/day/mouse), similar to that one of young mice (+1.4
microgram/day/mouse). The reduced zinc plasma level is restored to normal
values. These findings support the idea that the effect of melatonin on thymic
endocrine activity and peripheral immune functions may be mediated by the zinc
pool.