Histones deacetylation - new lead to degenerative diseases?

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This recent article (and that paper) discuss the link between histones abnormality and schizophrenia.

Histones acetylation reduction or "deacetylation" cripples the ability of DNA to encode proteins thus can affects the entire cellullar metabolic and regenerative apparatus, producing effects probably resembling genetic disorders.  (What are histones? Read here)

The study reports particulary strong histone anomaly among schizophrenic patients of young age. This suggests a possible neurodegenerative process indicating a possible mechanism of the pathology of a young brain, that may lead to schizophrenia later in life.

Questions to think about:

1. Could histone deacetylation anomaly lead to other common degenerative diseases?
2. How does it affect mitochondria?
3. Is there a connection between wheat histones (*) (or this) and human histones?

Few more facts about histones and neurological health:

- Since acetylation reduction is done by deacetylation enzymes called "deacetylase", inhibiting of deacetylase should restore the required level of histone acetylation. What are the common deacetylase inhibitors? Quote from the wiki article:

HDIs [Histone Deacetylase Inhibitors] fall into several groupings, in order of decreasing potency[6]:

• hydroxamic acids (or hydroxamates), such as trichostatin A,
• cyclic tetrapeptides (such as trapoxin B), and the depsipeptides,
• benzamides,
• electrophilic ketones, and 
• the aliphatic acid compounds such as phenylbutyrate and valproic acid.

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More references:
Scientists discover a brain cell malfunction in schizophrenia
( Note: the link above as well as the original article twit was posted on this blog )

Note (*): interestingly, wheat uses histone disruptors to fight funghi.  New wheat variety introduced in the last century was specifically bread to resist funghi and molds.  Recent wheat variety  = heart diesease and cancer.  Earlier wheat, 19-th century and back = no prob!  Or is it too far out to conclude that?

Latest news (9-Feb-2012):


Scientists make discovery related to atherosclerosis

A research team funded by the National Science Council achieved a breakthrough in molecular--targeted therapy of atherosclerosis by experimenting on the condition’s formation mechanism from the perspective of cardiovascular biodynamics.
The council said discoveries by the team led by National Health Research Institutes [Taiwan] researcher Chiu Jeng-jiann (裘正健) had been recognized by the prominent academic journal Physiological Reviews in a cover story last year.

...the team focused on discovering the mechanism of how different levels of blood flow shear stress could affect molecules related to atherosclerosis formulation. The team was able to demonstrate that oscillated shear stress can increase the performance of several types of histone deacetylase (HDAC) in the endothelium, modulating some transcription factors and gene transcription. A noteworthy discovery is that the third type of HDAC has the important function of modulating oxidation, inflammation and hyperplasia and can be seen as an important targeted therapy for the prevention or treatment of atherosclerosis, Chiu said.

Reference:
"Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives", JENG-JIANN CHIU AND SHU CHIEN, Physiol Rev 91: 327–387, 2011

Update (28/08/2013)


Age-Related Forgetfulness Tied to Diminished Brain Protein (RbAp48)

and


RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein.


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More starch more breast cancer recurrence

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New analysis based on WHEL study titled "Starch Intake May Influence Risk for Breast Cancer Recurrence" presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

Quotes:

“The results show that it’s not just overall carbohydrates, but particularly starch,” said Jennifer A. Emond, M.S., a public health doctoral student at the University of California, San Diego. “Women who increased their starch intake over one year were at a much likelier risk for recurring.”
Researchers conducted a subset analysis of 2,651 women who participated in the Women’s Healthy Eating and Living (WHEL) Dietary Intervention Trial, a plant-based intervention trial that enrolled about 3,088 survivors of breast cancer. WHEL researchers studied breast cancer recurrence and followed the participants for an average of seven years.
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The change in starch intake was “independent of dietary changes that happened in the intervention arm,” Emond said. “It is independent of more global changes in diet quality.”

I have to comment on the following quote: . “The WHEL dietary trial, even though it focused on fruits and vegetables, fiber and fat, didn’t really have a specific carbohydrate goal,” Emond said.

Time and time again studies focus on some secondary issues such as which particular vegetable or fruit selection affects some outcome while at the same time ignoring a major issue of macronutrient ratios! Such analyses often come as afterthoughts and end up using incomplete or partial data, just because the study proponents didn't bother to measure a major variable.  Now they seem surprized finding an "elephant" in their  lab! The biggest kicker is that vegetables - the one "healthy" diet aspect that they WHEL study authors did focused to the detriment of other more real issues, turned out to be irrelevant as far as cancer was concerned! (see the study I discuss further down)

Even though the results suffer from the fact that the original study methodology wasn't properly focused on the issue that mattered, the results are consistent with other studies. For example this one:

"Carbohydrates and the Risk of Breast Cancer among Mexican Women"
Isabelle Romieu, Eduardo Lazcano-Ponce, Luisa Maria Sanchez-Zamorano, Walter Willett and Mauricio Hernandez-Avila

The study showed a very strong breast cancer promoting effect of carbohydrate consumption: for every additional 1% of carbohydrate calories consumed above 52%, the relative risk of breast cancer was incrementally increasing by about 10%!

Consistent also with the Italian data:

"Dietary glycemic index, glycemic load, and the risk of breast cancer in an Italian prospective cohort study", Sabina Sieri et al.

The study showed that a 56% higher glycaemic load (from 96g/d to 150g/d) produced 2.53 times higher relative risk of breast cancer among Italian women.

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The following paper (also based on the same WHEL study as the headline study!) demonstrated that a low fat high vegetable diet was useless for fighting cancer!

"Influence of a Diet Very High in Vegetables, Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer." John P. Pierce, PhD; Loki Natarajan, PhD; Bette J. Caan, et al. The Women's Healthy Eating and Living (WHEL) Randomized Trial. JAMA. 2007;298:289-298.

Quote:

Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.

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Similar pattern with the ovarian cancer:

"Nutrient dietary patterns and the risk of breast and ovarian cancers." Edefonti V, et al., Int J Cancer. 2008 Feb 1;122(3):609-13.

... Cases were 2,569 breast cancers and 1,031 ovarian cancers hospitalized in 4 Italian areas between 1991 and 1999. Controls were 3,413 women from the same hospital network. Dietary habits were investigated through a validated food-frequency questionnaire. ... The animal products pattern and the unsaturated fats pattern were inversely associated with breast cancer (OR = 0.74, 95% CI: 0.61-0.91 and OR = 0.83, 95% CI: 0.68-1.00, respectively, for the highest consumption quartile), whereas the starch-rich pattern was directly associated with it (OR = 1.34, 95% CI: 1.10-1.65). The vitamins and fiber pattern was inversely associated with ovarian cancer (OR = 0.77, 95% CI: 0.61-0.98), whereas the starch-rich pattern was directly associated with it (OR = 1.85, 95% CI: 1.37-2.48). In conclusion, the starch-rich pattern is potentially an unfavorable indicator of risk for both breast and ovarian cancers, while the animal products and the vitamins and fiber patterns may be associated with a reduced risk of breast and ovarian cancers, respectively.

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[side issue: carbs and HDL putting it here as a reminder for myself to write some more on it]
"Carbohydrate intake and HDL in a multiethnic population." Am J Clin Nutr. 2007 Jan;85(1):225-30.

"Previous research has identified ethnic differences in cholesterol and other blood fat levels that couldn't be explained by genes, obesity, lifestyle factors or diet, Merchant and his team note, but these analyses usually looked at dietary fat, not carbohydrate consumption"

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Another Italian study, similar pattern:

"Intake of macronutrients and risk of breast cancer."
Franceschi S, Favero A, Decarli A, Negri E, La Vecchia C, Ferraroni M, Russo A, Salvini S, Amadori D, Conti E, Montella M, Giacosa A.
Lancet. 1996 May 18;347(9012):1351-6.

... FINDINGS: The risk of breast cancer decreased with increasing total fat intake (trend p ? 0.01) whereas the risk increased with increasing intake of available carbohydrates (trend p=0.002). The odds ratios for women in the highest compared with the lowest quintile of energy-adjusted intake were 0.81 for total fat and 1.30 for available carbohydrates. Starch was the chief contributor to the positive association with available carbohydrates. ... Conversely, the intakes of saturated fatty acids, protein, and fibre were not significantly associated with breast-cancer risk. ...

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Update (25-12-2011)

I am slapping this paper here quickly for the reference although it is not strictly on-topic (thanks Kiran)

Mean life span of CR sucrose-fed rats was significantly greater than all other groups [including starch fed CR]

Feed	Corn starch	Sugar
100% cal	720	659
60% cal	726	890

The rats diet consisted of 14% protein, 10% fat, and 66% sucrose or cornstarch. The numbers are the average lifespans of rats in days (standard deviation is about +/-20days). 100% cal means an ad-libidum diet. 60% cal = calorie-restriction diet.
(this study needs a discussion)
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Arterial plaque = glucose + insulin, C14 traced study

Atheroma (from wiki)

A "blast from the past": two old forgotten papers that were never followed up, as far as I was able to find.  I wonder why not?

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INSULIN STIMULATED LIPOGENESIS IN ARTERIAL TISSUE IN RELATION TO DIABETES AND ATHEROMA
R. W. Stout, Lancet p702,1968

Summary

Discussion (p1 of 2)

Discussion (p2 of 2)

INSULIN STIMULATION OF CHOLESTEROL SYNTHESIS BY ARTERIAL TISSUE

R.W. Stout, Lancet p467,1969

Summary

Discussion (p1 of 2)

Discussion (p2 of 2)

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Dav0 found a more recent paper by Stout (thanks):


Insulin and Atheroma: 20-Yr Perspective, Robert W Stout, MD, DSc, FRCP

Quote:

Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower highdensity lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels.

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