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Dean Pomerleau

Adult-onset CR Protects Against Parkinson's-like Motor Decline

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Ever since CR pioneer Roy Walford died of amyotrophic lateral sclerosis (ALS - or something resembling ALS), there has been some concern that CR may not protect against, and may in fact hasten, neurodegenerative diseases, particularly those involving dopaminergic neurons, like ALS, Parkinson's Disease (PD) and Multiple Sclerosis (MS).

 

This new study [1] by Ingram et al posted by James in his latest weekly CR research update (thanks James!), suggests otherwise. It found that adult-onset CR in rats was protective against bradykinesia, a slowness of movement which is a hallmark of Parkinson's disease. They also found elevated levels of dopamine in an important brain region implicated in PD, the substantia nigra. This result supports an earlier, perhaps more germane finding from a study of primates done by Ingram's group in 2004 [2]. In [2], Ingram et al found that 30% CR for six months in adult male rhesus monkeys protected against a drop in dopamine level and dopamine neuron cell death when the (unfortunate  :(xyz) monkeys were exposed to a neurotoxin that mimics Parkinson's Disease in primates.

 

So overall that is more encouraging news for CR & brain health - on top of the finding of preserved white matter by CR I reported on earlier. 

 

In researching this post, I came across a review article [3] about a possible link between these three neurodegenerative diseases (PD, ALS & MS) and iodine. It observed that in regional population studies, long-term dietary iodine deficiency is associated with all three of these diseases, and may be explained by iodine deficiency interfering with dopamine and dopaminergic neurons. Whether this link holds up under scrutiny I'm not sure, but it is another possible reason to make sure one isn't deficient in iodine.

 

Unfortunately, iodine is not well represented in the USDA (or any other) food database. For many people who consumed a low sodium diet, and in particular don't consume iodized salt, iodine deficiency is a real concern. That's why I supplement with the RDA (150mcg) of iodine per day. Note - high sodium processed foods typically do not contain iodine, so even the general population may be iodine deficient if they aren't eating foods with iodized salt.

 

--Dean

 

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[1] Neurobiol Aging. 2015 Oct 19. pii: S0197-4580(15)00495-9. doi:

10.1016/j.neurobiolaging.2015.10.006. [Epub ahead of print]

Initiation of calorie restriction in middle-aged male rats attenuates
aging-related motoric decline and bradykinesia without increased striatal
dopamine.

Salvatore MF(1), Terrebonne J(2), Fields V(3), Nodurft D(3), Runfalo C(2),
Latimer B(3), Ingram DK(2).

Aging-related bradykinesia affects ∼15% of those reaching age 65 and 50% of those
reaching their 80s. Given this high risk and lack of pharmacologic therapeutics,
noninvasive lifestyle strategies should be identified to diminish its risk and
identify the neurobiological targets to reduce aging-related bradykinesia.
Early-life, long-term calorie restriction (CR) attenuates aging-related
bradykinesia in rodents. Here, we addressed whether CR initiation at middle age
could attenuate aging-related bradykinesia and motoric decline measured as
rotarod performance. A 30% CR regimen was implemented for 6 months duration in
12-month-old male Brown-Norway Fischer 344 F1 hybrid rats after establishing
individual baseline locomotor activities. Locomotor capacity was assessed every 6
weeks thereafter. The ad libitum group exhibited predictably decreased locomotor
activity, except movement speed, out to 18 months of age. In contrast, in the CR
group, movement number and horizontal activity did not decrease during the
6-month trial, and aging-related decline in rotarod performance was attenuated.
The response to CR was influenced by baseline locomotor activity. The lower the
locomotor activity level at baseline, the greater the response to CR. Rats in the
lower 50th percentile surpassed their baseline level of activity, whereas rats in
the top 50th percentile decreased at 6 weeks and then returned to baseline by 12
weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be
greater in the CR group and observed a modest increase only in substantia nigra
with no group differences in striatum, nucleus accumbens, or ventral tegmental
area. These results indicate that initiation of CR at middle age may reduce
aging-related bradykinesia, and, furthermore, subjects with below average
locomotor activity may increase baseline activity. Sustaining nigral dopamine
neurotransmission may be one component of preserving locomotor capabilities
during aging.

Copyright © 2015 Elsevier Inc. All rights reserved.

PMID: 26610387 

 

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[2] Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18171-6. Epub 2004 Dec 16.

Caloric restriction increases neurotrophic factor levels and attenuates
neurochemical and behavioral deficits in a primate model of Parkinson's disease.

Maswood N(1), Young J, Tilmont E, Zhang Z, Gash DM, Gerhardt GA, Grondin R, Roth
GS, Mattison J, Lane MA, Carson RE, Cohen RM, Mouton PR, Quigley C, Mattson MP,
Ingram DK.

Author information:
(1)Laboratory of Neurosciences, National Institute on Aging Intramural Research
Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.

Comment in
Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):17887-8.

We report that a low-calorie diet can lessen the severity of neurochemical
deficits and motor dysfunction in a primate model of Parkinson's disease. Adult
male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30%
caloric restriction (CR)] or an ad libitum control diet after which they were
subjected to treatment with a neurotoxin to produce a hemiparkinson condition.
After neurotoxin treatment, CR monkeys exhibited significantly higher levels of
locomotor activity compared with control monkeys as well as higher levels of
dopamine (DA) and DA metabolites in the striatal region. Increased survival of DA
neurons in the substantia nigra and improved manual dexterity were noted but did
not reach statistical significance. Levels of glial cell line-derived
neurotrophic factor, which is known to promote the survival of DA neurons, were
increased significantly in the caudate nucleus of CR monkeys, suggesting a role
for glial cell line-derived neurotrophic factor in the anti-Parkinson's disease
effect of the low-calorie diet.

PMCID: PMC539733
PMID: 15604149

 

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[3] Journal of Orthomolecular Medicine Vol. 14, 3rd Quarter 1999

 

Parkinson’s Disease, Multiple Sclerosis and Amyotrophic Lateral Sclerosis: The Iodine-Dopachrome-Glutamate Hypothesis

 

Harold D. Foster

 

Full text: http://orthomolecular.org/library/jom/1999/articles/1999-v14n03-p128.shtml

 

Abstract
 
Background. Globally, Parkinsonism, multiple sclerosis and amyotrophic lateral sclerosis mortalities tends to increase with latitude. These disorders also display a north-south gradient in the coterminous United States. This spatial distribution suggests their etiologies are significantly influenced by one or more geographical variables.
 
Methods. Pearson’s correlation was used to compare mortalities, at the state scale, in the United States, from these three neurologic disorders and the spatial patterns of 81 other diseases and 219 environmental variables.
 
Results. The resulting correlations suggest that mortality from Parkinsonism, multiple sclerosis and amyotrophic lateral sclerosis occurs most often in recently glaciated, iodine deficient regions, that were formerly marked by elevated goiter prevalence.
 
Conclusions. Long-term iodine deficiency appears linked to abnormalities in the dopaminergic system that include an increased number of dopamine receptors. It is argued that this raises susceptibility to dopamine oxidation which, in turn, causes deficiencies of the antioxidant enzymes Cu/Zn superoxide dismutase, glutathione peroxidase and catalase. Dopamine deficiency also leads to elevated cytotoxic glutamate levels. Implications of the iodine-dopachrome-glutamate hypothesis, for treatment of these three neurologic disorders, are then discussed. Possible interventions include the use of levodopa, vitamin B3, Coenzyme Q10, various antioxidants, amino acids, iodine and glutamate antagonists.
 
Key words: Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, glaciation, iodine, goiter, dopamine, dopachrome, glutamate, oxidative stress.

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