Neuroprotective signaling and the aging brain: take away my food and let
me run
Mark P. MattsonA mattsonm@grc.nia.nih.gov
Laboratory of Neurosciences, National Institute on Aging Gerontology
Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA
http://www.neuroscion.com/fulltext/JOURNAL.BRES.bri00003_00068993_unassign
_19153
It is remarkable that neurons are able to survive and function for a
century or more in many persons that age successfully. A better
understanding of the molecular signaling mechanisms that permit such cell
survival and synaptic plasticity may therefore lead to the development of
new preventative and therapeutic strategies for age-related
neurodegenerative disorders. We all know that overeating and lack of
exercise are risk factors for many different age-related diseases
including cardiovascular disease, diabetes and cancers. Our recent studies
have shown that dietary restriction (reduced calorie intake) can increase
the resistance of neurons in the brain to dysfunction and death in
experimental models of Alzheimer's disease, Parkinson's disease,
Huntington's disease and stroke. The mechanism underlying the beneficial
effects of dietary restriction involves stimulation of the expression of
'stress proteins' and neurotrophic factors. The neurotrophic factors
induced by dietary restriction may protect neurons by inducing the
production of proteins that suppress oxyradical production, stabilize
cellular calcium homeostasis and inhibit apoptotic biochemical cascades.
Interestingly, dietary restriction also increases numbers of
newly-generated neural cells in the adult brain suggesting that this
dietary manipulation can increase the brain's capacity for plasticity and
self-repair. Work in other laboratories suggests that physical and
intellectual activity can similarly increase neurotrophic factor
production and neurogenesis. Collectively, the available data suggest the
that dietary restriction, and physical and mental activity, may reduce
both the incidence and severity of neurodegenerative disorders in humans.
A better understanding of the cellular and molecular mechanisms underlying
these effects of diet and behavior on the brain is also leading to novel
therapeutic agents that mimick the beneficial effects of dietary
restriction and exercise.
Stay hungry,
--J. R.
3M TA3
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