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Glucose restriction extends healthy cellular life span
University of Alabama Department of Biology professor Trygve Tollefsbol, PhD, DO and colleagues cultured healthy and precancerous human lung cells with normal or significantly restricted glucose for several weeks. "In that time, we were able to track the cells' ability to divide while also monitoring the number of surviving cells,” Dr Tollefsbol reported. “The pattern that was revealed to us showed that restricted glucose levels led the healthy cells to grow longer than is typical and caused the precancerous cells to die off in large numbers.” Dr Tollefsbol and his associates found that while there was an increase in the expression of the human telomerase reverse transcriptase gene and a decrease in the expression of the anticancer protein p16 in normal glucose restricted cells, opposite effects were observed in precancerous cells that were glucose-restricted. "The healthy cells saw their telomerase rise and p16 decrease, which would explain the boost in healthy cell growth,” Dr Tollefsbol noted. “The gene reactions flipped in the precancerous cells with telomerase decreasing and the anticancer protein p16 increasing, which would explain why these cancer-forming cells died off in large numbers." "Our results not only support previous findings from the feeding of animals but also reveal that human longevity can be achieved at the cellular level through caloric restriction," he added. "The hope is that this UAB breakthrough will lead to further discoveries in different cell types and facilitate the development of novel approaches to extend the lifespan of humans." —D Dye High methionine diet may increase Alzheimer’s disease risk
“When methionine reaches too high a level, our body tries to protect itself by transforming it into a particular amino acid called homocysteine,” explained lead researcher Domenico Praticò, who is an associate professor of pharmacology at Temple University. “The data from previous studies show — even in humans — when the level of homocysteine in the blood is high, there is a higher risk of developing dementia. We hypothesized that high levels of homocysteine in an animal model of Alzheimer's would accelerate the disease." Dr Praticò and colleagues fed one group of seven month old mice a high methionine diet and gave another group a regular diet for 8 months. At 15 months of age, which is the equivalent of a 70 year old human, serum homocysteine levels were measured. “We found that the mice with the normal diet had normal homocysteine levels, but the mice with the high methionine diet had significantly increased levels of homocysteine, very similar to human subjects with hyperhomocysteinemia,” Dr Praticò reported. “The group with the high methionine diet also had up to 40 percent more amyloid plaque in their brains, which is a measurement of how much Alzheimer’s disease has developed.” “Stopping one’s intake of methionine won’t prevent Alzheimer’s,” he added, “but people who have a diet high in red meat, for instance, could be more at risk because they are more likely to develop this high level of circulating homocysteine.” —D Dye Antioxidants decrease colorectal polyp recurrence
The study enrolled 411 participants aged 25 to 75 who did not have cancer or other life-threatening illnesses. Subjects were randomized to receive a daily placebo or a supplement containing 6000 international units vitamin A, 180 milligrams vitamin C, 30 milligrams vitamin E, 200 micrograms selenium and 30 milligrams zinc. Colonoscopy was repeated one, three and five years after the beginning of the study, and according to current guidelines thereafter over follow-up. Of 311 participants for whom follow-up information was available in June of this year, adenomas recurred in 98 and 2 subjects had invasive cancer. The risk of adenoma recurrence was 41 percent lower for those who received the antioxidant supplement than those who received a placebo. Among those in whom advanced adenomas were originally detected, there was a 10 times lower risk of advanced adenoma recurrence compared with the placebo group. "Our study is the first intervention trial specifically designed to evaluate the efficacy of the selenium-based antioxidant compound on the risk of developing metachronous adenomas," noted Dr Bonelli, who is the head of the unit of secondary prevention and screening at Italy’s National Institute for Cancer Research. "It is noteworthy that the benefit observed after the conclusion of the trial persisted through 13 years of follow up." An investigation of genetic alterations that could account for the study’s findings is currently underway. —D Dye Delay aging, delay Alzheimer’s
Andrew Dillin, PhD of the Salk Institute for Biological Studies and his colleagues discovered that reducing insulin/insulin growth factor (IGF) signaling, which is a pathway through which aging has been delayed in laboratory animals, results in protection from the signs of Alzheimer’s disease in mice modified to carry human genes for the disease. In the brains of the animals in which insulin/IGF signaling was reduced, the amyloid plaques that characterize Alzheimer’s disease were still present, yet the plaques were more tightly packed than what is usually seen in the disease. "We expected to see less plaque in the protected mice," Dr Dillin remarked. "Instead we saw the same number of plaques, but there was a qualitative difference in how they looked. They were condensed so that they took up less area in the brain." The insulin/insulin growth factor pathway controls two transcription factors, FOXO and HSF-1. Increasing these transcription factors could be a drug target for Alzheimer’s disease prevention. "This highly conserved pathway plays a crucial role in the regulation of lifespan and youthfulness across many species, including worms, flies, and mice and is linked to extreme longevity in humans," lead author Ehud Cohen, PhD explained. "The reporting of this work is a celebration for the entire field of aging researchers,” he affirmed, “as it validates the long-held hypothesis that genetic and pharmacologic changes to create a healthy lifespan, or 'healthspan,' can greatly reduce the onset of some of the most devastating diseases that afflict mankind.“ —D Dye Higher omega-3 fatty acid intake correlated with reduced colon cancer risk
Dr Kim and colleagues at the University of North Carolina compared 716 Caucasian and 213 African American men and women with distal colorectal cancer to 787 Caucasian and 156 African American control subjects for their study. Dietary questionnaire responses were evaluated to determine omega-3 and other polyunsaturated fatty acid intake over the previous year. For participants whose intake of omega-3 fatty acids was among the top 25 percent of participants, a 39 percent lower risk of the disease was observed in comparison with subjects whose intake was in the lowest fourth. The protective effect was limited to Caucasians. "We were surprised that the association was not also observed among blacks," Dr Kim remarked. "We considered several possible explanations but were not able to account for this difference with the data we had. This finding warrants future study, but we should be careful about drawing conclusions about potential racial differences in the benefit from long-chain omega-3 fatty acids from this study." "Experimental data have shown benefits of long-chain omega-3 fatty acids in colorectal carcinogenesis, ranging from reduced tumor growth, suppression of angiogenesis and inhibition of metastasis," Dr Kim noted. "Our finding of inverse association between dietary intakes of long-chain omega-3 fatty acids and distal large bowel cancer in white participants adds additional support to the hypothesis." —D Dye Breast cancer patients who consume soy experience improved survival
Xiao Ou Shu, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee and colleagues examined data from 5,033 participants in the Shanghai Breast Cancer Survival Study who were surgically treated for breast cancer. Participants enrolled between 2002 and 2006 and were followed through June, 2009, during which three interviews were conducted to reassess lifestyle exposures and disease progression. Dietary questionnaire responses were analyzed for the intake of soy protein and soy isoflavones. Over a median follow-up of 3.9 years, 444 total deaths and 534 recurrences or deaths from breast cancer were documented. The use of tamoxifen, and, interestingly, hormone therapy, were associated with improved survival. For women whose intake of soy protein was among the top 25 percent of participants, there was a 29 percent lower risk of dying over follow-up and a 32 percent lower risk of recurrence compared to those whose intake was in the lowest fourth. When soy isoflavones were evaluated, the risk of dying over follow-up was 21 percent lower and the risk of recurrence was 23 percent lower for those whose intake was highest. The authors conclude that soy foods are safe and of potential benefit to women with breast cancer. However, in an accompanying editorial, Rachel Ballard-Barbash, MD, MPH, and Marian L. Neuhouser, PhD remark that the effects of soy dietary supplements are still unknown. —D Dye Branched chain amino acids show promise for the treatment of traumatic brain injury
Branched chain amino acids include valine, leucine and isoleucine. These amino acids are precursors to the neurotransmitters glutamate and gamma-aminobutyric acid, which balance brain activity. In research involving humans with brain injuries, functional improvements were associated with branched chain amino acids administered intravenously. In the current study, the researchers compared amino acid levels in the hippocampuses of mice that received injuries to this area with animals that received sham injuries. (The brain’s hippocampus, which is involved in higher learning, is frequently damaged during traumatic brain injury.) Of 18 amino acids evaluated, only the three branched chain amino acids were found to be significantly lower compared to levels measured in the sham injured animals. Mice given branched chain amino acids in their drinking water after brain injury showed similar learning responses to uninjured mice, and electrophysiological experiments with brain tissue demonstrated a normal balance of neural activity in the hippocampus. "The electrophysiological results were consistent with what we saw in the animals' functional recovery," Dr Cohen noted. "We have shown in an animal model that dietary intervention can restore a proper balance of neurochemicals in the injured part of the brain, and simultaneously improves cognitive performance," Dr Cohen concluded. She suggests that branched chain amino acids administered as an oral supplement could be more beneficial than the intravenous route, which may flood brain receptors. A trial of oral branched chain amino acids in patients with traumatic brain injury is planned for next year. —D Dye December 04, 2009Green tea compound helps destroy amyloid
Writing in the December 9, 2009 issue of Nature Chemical Biology, Dr Martin L Duennwald of Boston Biomedical Research Institute and his colleagues at the University of Pennsylvania School of Medicine report the effect of EGCG and DAPH-12 on amyloids made by a yeast amyloid protein that produces structures similar to those found in damaged human brains. Although EGCG alone dissolved weak amyloid structures, it did not dissolve all of the stronger amyloids tested and caused some of them to develop resistance to the compound. However, the combination of EGCG with DAPH-12 resulted in the destruction of all of the amyloids tested. "These findings are significant because it is the first time a combination of specific chemicals has successfully destroyed diverse forms of amyloids at the same time," noted Dr Duennwald, who led the study with Dr James Shorter of University of Pennsylvania School of Medicine’s department of biochemistry and biophysics. "Our findings are certainly preliminary and we need further work to fully comprehend the effects of EGCG in combination with other chemicals on amyloids. Yet, we see our study as a very exciting initial step towards combinatorial therapies for the treatment of amyloid-based diseases." —D Dye Selenium supplementation normalizes oxidative stress in women at high risk of breast cancer
“It has long been known that the anticancer properties of selenium may involve inhibition of oxidative stress ,” the authors explain. “Therefore, investigating the chemopreventing effect of this nutritional supplement in high-risk individuals and cancer patients by means of biomarkers that would signal changes in oxidative stress/oxidative DNA damage may be an important approach to understanding the mechanisms of selenium action and cancer prevention.” The researchers conducted a double-blinded trial involving 136 women with BRCA1 mutations who did not have cancer, 28 BRCA-1 mutation carriers with breast or ovarian cancer, and 91 healthy women without the mutation. The mutation carriers were divided to receive 300 micrograms per day selenium or a placebo for one year. White blood cell 8-oxodG, a measure of oxidative stress and DNA damage, was found to be higher in BRCA-1 carriers compared to the control group. Selenium supplementation was associated with a significant reduction in 8-oxodG and an increase in urinary 8-oxoGua, a product of DNA repair, in BRCA-1 carriers, however the reduction was only determined to be significant in those without cancer who underwent removal of their ovaries and Fallopian tubes adnexectomy). “Oxidative DNA damage and the risk to develop breast cancer in BRCA1 mutation carriers may be reduced in selenium supplemented patients who underwent adnexectomy,” the authors conclude. —D Dye
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Writing in an article published online on December 2009 in 
Research described in an article published online in the journal 
At a presentation at the Frontiers in Cancer Prevention Research Conference held in Houston December 6-9, 2009 Luigina Bonelli, MD reported that a combination of antioxidants consumed daily over a 5 year period reduced the risk of recurring colorectal adenomas (polyps) in subjects who had already had one or more adenomas removed during colonoscopy. While most adenomas never become cancerous, detection and removal of polyps is one of the most effective means to prevent the development of 
An article published in the December 11, 2009 issue of the journal 
In a presentation at the Frontiers in Cancer Prevention Research Conference, held December 6th though the 9th this year in Houston, Sangmi Kim, PhD of the National Institute of Environmental Health Sciences reported the finding of a reduction in the risk of distal 
More evidence for the safety of soy consumption by breast cancer patients has been provided by the results of a study published in the December 9, 2009 issue of the 
An article published online on December 7, 2009 in the 
A compound known as epigallocatechin gallate (EGCG) found in green tea, along with a previously researched compound known as DAPH-12 have been shown to dissolve amyloid when administered in combination. Amyloids are proteins that form plaques in the brain that may be responsible for 
In the November, 2009 issue of the journal 