Impact of Dietary Restriction on Brain Aging and Neurodegenerative Disorders: Emerging Findings from Experimental and Epidemiological Studies

Summary: Calorie restriction helps mice and rat models of Alzheimer's, Parkinson's and stroke. 2-doxyglucose does too.

Interestingness: 2

Paper by Mark P Mattson in the Journal of Anti-Aging Medicine, Volume 2, Issue 4, Winter 1999.

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Rats and mice models of Alzheimer's disease (AD) did better when they were on a calorie restriction diet (CR). The same for Parkinson's disease (PD). Also for Huntington disease (HD). Also for rats given a stroke. I don't like the models, except the one for stroke, so I don't care much about these results.

They think this effect comes from over-expression of heat shock proteins (HSP-70) when glucose goes low. When given 2-deoxygluose (2-DG), a modified glucose that competes with glucose for the energy chain enzymes but is not able to be broken down properly (http://readingrejuvenationresearch.blogspot.com/2010/07/2-deoxy-d-glucose-feeding-in-rats.html), rats and mice also did better in the AD, PD and stroke models, even though they lived under all-you-can eat buffet conditions.

Finally, some lame-sounding correlation studies between caloric intake surveys with PD, AD and stroke are listed.
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Abstract follows:

Although dietary restriction (DR) extends life span and reduces levels of cellular oxidative stress in several different organ systems of laboratory rodents and monkeys, its impact on the brain is unknown. As is the case with age-related disorders in other organ systems (e.g., cardiovascular disease, diabetes, and many cancers), neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and stroke involve increased levels of cellular oxidative stress and metabolic compromise. Recent studies of experimental rat and mouse models of AD, PD, and stroke have shown that DR increases resistance of neurons to dysfunction and degeneration. DR can attenuate age-related and disease-specific deficits in cognitive and motor functions in rodents. The available data suggest at least two possible mechanisms whereby DR protects neurons. One involves decreased levels of mitochondrial oxyradical production, and the second involves induction of the expression of "stress proteins" and neurotrophic factors. The latter mechanism is supported by data showing that the neuroprotective effect of DR can be mimicked by administration of 2-deoxyglucose to animals fed ad libitum. Recent findings in epidemiological studies of human populations suggest that individuals with a low daily calorie intake have reduced risk for AD and PD. Collectively, the available data suggest that DR may prove beneficial in reducing both the incidence and severity of neurodegenerative disorders in humans.

Diabetes and Hypertension (Syndrome X) as an Increasing Risk Factor for Cerebrovascular Aging in Japan

Summary: Diabetes, hypertension and high serum GOT highly associated with stroke. High cholesterol, salt intake, calorie intake, smoking, alcohol consumption and family history were not associated with stroke.

Paper by Y Wada, M Tsukada and A Koizumi in Journal of Anti-Aging Medicine, Volume 1, Issue 1, Spring 1998.

This is a standard epidemiological study that follows about 7500 over 35 year olds from the Akita prefecture in Japan for 3 to 5 years (((I can't tell exactly. They measured them between '89 and '91 and followed the death registry till '94))) looking for correlations between a number of health and behavioural measures, and stroke. They observed 123 strokes. There were also 94 strokes among their subjects prior to enrolment but they excluded those people and their strokes from the analysis with respect to stroke.

Akita is the high stroke, high alcohol consumption region of Japan. Going by the characteristics table in the paper, the men smoke and drink, and the women do neither. About 3% of the people in the study had diabetes, about half had hypertension and about 2.5% had both. The researchers focused a bit on that combination of diabetes and hypertension called Syndrome X (((which I think is commonly called metabolic syndrome nowadays))), and set it up as another variable to measure correlation.

Results of relative risk of stroke expressed as odds ratio were as follows:

(trait - what is ratio measuring - odds ratio (95% confidence interval)

• Hypertension - yes/no - 3.78 (2.4 - 5.97)
• Diabetes - yes/no - 2.87 (1.51 - 5.44)
• Both (Syndrome X) - yes/no - 7.42 (3.16 - 17.42) (((ratio is people with both to people with neither)))
• serum GOT - >40 IU/L / 8-40 - 4.00 (2.00 - 8.00)
• age class - >60 / 50-59 / <>

All the following were between 0.7 and 1.3:

• Hypercholesterolemia (> 220 mg/dl)
• BMI
• Father, mother or sibling with diabetes, hypertension or stroke
• Miso soup intake
• Salty food intake
• Changes in habits of food intake or salt intake
• Drinking habit
• Smoking habit
• Physical inactivity

Notes regarding models:
Gender, age, diabetes and hypertension were regressed together.
All other variables were adjusted for age and gender only.

(((Serum GOT (aspartase aminotransfarase) is used as a marker for liver damage, but can also be due to heart damage (or kidney, or brain, or muscle in general). They seemed to take it as a marker for alcohol related liver damage)))


They also calculated relative risks of syndrome X of those same variables. (((I don't consider them as interesting)))


(((Conclusion: Same as summary. Watch out for hypertension, but salt isn't the answer.)))

Abstract below:

Recently, there has been an increased incidence of diabetes mellitus in Japan, where the rate of stroke is high. We reviewed the risk factors of stroke with special reference to "Syndrome X." We reviewed a population-based cohort from 1989 through 1991 that consisted of 7,456 subjects over the age of 35 at Akita, a stroke-prevalent rural district in the northeastern part of Japan known to have the shortest longevity and the highest alcohol consumption in the country. Baseline data were obtained by a questionnaire, physical exams, and blood serum tests. Physical characteristics were similar to national norms, although the proportion of heavy (ex-)drinkers was higher (72.5% for male; 12.0% for female). The prevalence of diabetes mellitus, hypertension, and Syndrome X (defined as diabetes mellitus plus hypertension) was 3.0%, 47.0%, and 1.9%. Observed prevalence of Syndrome X was higher than the expected value. The tendency to disease-clustering was strong in young females. The risk factors of Syndrome X were high body mass index (BMI); a family history of diabetes, hypertension or Syndrome X; regular drinking; high serum GOT; and less walking activity (odds ratio: 1.15, 3.91, 1.62, 4.76, 1.35, 3.97, and 1.21). Stressful occupational environment, feelings of daily stress, a tendency to get angry, and snoring also increased risk of Syndrome X. By 1995,129 stroke cases were observed in the cohort; 123 cases were the first episode. Diabetes mellitus, hypertension, Syndrome X, high BMI, high serum GOT, and less walking activity were associated with significantly higher relative risks for stroke (odds ratio: 2.87, 3.78, 7.42, 1.07, 4.00, and 1.28). Intake of salty foods and hypercholesterolemia were not associated with a higher incidence. The population-attributable risks of stroke related to diabetes mellitus, hypertension, Syndrome X, and high serum GOT were 5.2%, 56.7%, 10.6%, and 7.8%. Syndrome X proved to have the highest relative risk of stroke. Important and controllable risk factors of Syndrome X and stroke were habitual alcohol intake with high serum GOT and less walking activity. Genetic factors were also presumably important to the prevention of Syndrome X. These factors must be considered in strategies aimed at preventing cerebrovascular aging.