PharmacoNutrition Reviewed

Source: Neuroscience Letters 439 (2008): 208-211
Article Type: Original Research
Authors: Kushida S et al.

In their latest paper, Kushida and colleagues examined in Amyloid beta-infused rats the effect of soft-diet feeding on two parameters which are typically affected in Alzheimer’s Disease (AD) patients

a) the release of the neurotransmitter dopamine
b) the learning ability and memory performance

Rats were fed either a hard (standard) or soft diet for 3 weeks days. During the last 2 weeks, rat brains were continuously infused with Abeta, the putative main culprit in AD.

“We found no significant differences in the basal level of dopamine release in the hippocampus between soft- and hard-diet-fed groups; however, the dopamine release evoked by high-K Ringer’s solution was significantly different between the soft- and hard-diet-fed groups. The increase of dopamine release in the hard-diet-fed group reached 420%; however, that in the soft-diet-fed group reached only 260%. In AD model rats, dopamine release in the soft-diet-fed group was significantly less than that of the hard-diet-fed group.”

After assessing the rats in the co-called step-through passive avoidance test, the authors conclude that:

“Our results also suggest that soft-diet feeding impairs learning ability and memory in AD rats; however, the underlying mechanism is unknown. One possible explanation is that the present results may be caused by the changes of activity in sensori-motor pathways of soft-diet-fed rats.”

How does this now relate to AD patients?

“Elderly people lose many teeth as they age. The loss of teeth not only forces them to eat soft foods, but also correlates to the development of senile dementia and Alzheimer’s disease (AD).”

So might one speculate that a rather early move in life towards the consumption of soft food triggers the onset of AD? An interesting idea – although much research is needed to establish this link of cause and consequence.

More on AD and diet (i.e. coffee intake) can be found here.

Source: Science 317: 516-519
Article Type: Original Research
Authors: Outeiro et al.
As members of the histone deacetylase family of proteins, sirtuins play a prominent role in aging. Seven sirtuins, SIRT1 to SIRT7, have been identified in humans.
Most research on sirtuin-mediated modulation of life span focussed on the activation of sirtuins (especially SIRT1), e.g. via resveratrol, a stilbene present in red wine and other food plants.
In the July 27 issue of Science, Outeiro et al. now report on the rescue of alpha-synuclein-induced neurotoxicity in models (cell cuture and Drosophila m.) of Parkinson’s disease (PD) due to inactivation of SIRT2. The mechanism of action might be due to 1) alterations in alpha-synuclein aggregation and 2) microtubule stabilization. Whether SIRT2 inactivation also directly affects life span, however, has not been addressed in this article. Those interested in this aspect might want to have a look at a recent paper published by Wang et al. (Aging Cell 6(4), 2007), where the authors descibe elevated SIRT2 expression in response to caloric restriction, a classical ‘inducer’ of longevity.

If you are looking for more information on PD, have a look at the PD Blog Network.

Image taken from: www.pdmdcenter.com

Source: Biogerontology (200), 7: 307-314
Article Type: Review
Authors: V Frazzini, E Rockabrand, E Mocchegiani, SL Sensi

Image Taken From:
http://upload.wikimedia.org/wikipedia/commons/thumb/7/79/
Zinc_finger_DNA_complex.png/300px-Zinc_finger_DNA_complex.png

Zinc (Zn) is the second most abundant trace element in the body (total amount approx. 2 g) and essential for human survival. Zics’s role in human physiology include a) catalytic (about 300 enzymes are Zn-dependent), b) structural (‘Zn-finger motifs in proteins) and c) regulatory (metallothioneins, immunes response, insulin metabolism) function.
Currently, a daily Zn intake of 10 mg is considered adequate. Dietary surveys showed widespread, worldwide prevalence of inadequate Zn intakes with, however, considerably lower risk in North America and Europe than other parts of the world.
Well-known clinical Zn-deficiency symptoms include a) skin lesions & delayed wound healing, b) immune deficiency, c) impaired taste and appetite and d) eye lesions. Consequently, Zn is nowadays commonly found in dietary/food supplements.

As with any nutrient, too much is too much. This brings us to the recent article by Frazzini et al. who asked the question whether Zn could actually be a link between oxidative stress and brain aging.
What caught my interest are the in nerve cells observed regional differences of Zn dysregulation, which have been suggested to trigger ‘normal’ brain aging and especially neurodegeneration.
The figure below summarizes the key aspects of the mechanisms possibly explaining Zn’s potential to induce brain cell death.

Does this now mean we should be aware of our daily Zn intake to protect our brain?
Most probably not. Although Zn toxicity (here especially peripheral symptoms) has been described in individuals repeatedly consuming more than 50 mg per day, the blood brain barrier, which regulates Zn homeostasis of the brain, is comparatively impermeable to changes in the concentration of blood metal ions. This does, of course, not mean that one cannot deplete the brain of Zn when significantly cutting down oral Zn intake.
In terms of neurodegeneration, for example Alzheimer’s disease, current believe is that the toxic effects of Zn are due to disruption of the brain endogenous Zn homeostasis, a hypothesis which is supported by studies in neuronal-specific Zn-transporter knockout mice.

As a general comment, I think Zn deficiency is a far bigger problem that chronic Zn overload for the majority of people. So, despite the increasing number of studies linking brain Zn with neurodegeneration, the above mentioned facts hopefully made clear that there’s only little - better to say no - hope of preventing neurodegeneration by reducing Zn intake. Vice versa, increase Zn intake above the current RDA to boost the body’s antioxidant and subsequently disease resistance, as suggested in various publications, must also be discouraged due to lack of evidence.

FIGURE: Mechanism of Zn-mediated Neurodegeneration