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SUNDAY, Jan. 27 (HealthDay News) -- A once-promising pathway for research into preventing and treating Alzheimer's disease may have been derailed by a surprise chemical finding, researchers report.

Scientists in laboratories around the world have been investigating drug candidates called amyloid inhibitors, which many experts believed could keep proteins such as amyloid-beta from sticking together in brain tissue.

This type of "sticky" protein plaque build-up is a hallmark of Alzheimer's disease. It also characterizes brain illnesses such as Huntington's disease and "mad cow" disease.

But the new study, published Jan. 27 in the journal Nature Chemical Biology, may sound an unexpected death knell for amyloid inhibitor research.

In the study, a team of chemists at the University of California, San Francisco, found that these candidate drugs form large, unwieldy clumps themselves, rendering them useless as targeted therapy against amyloid in the brain.

High-tech research in the lab is revealing that typical amyloid inhibitors "seem to act not in the way people expect them to and want them to," explained study senior author Brian Shoichet, professor of pharmaceutical chemistry at UCSF.

Once these drugs aggregate into clumps, "they no longer have the right pharmacology, they won't cross the [brain's] membrane barriers, and they inhibit everything -- any protein will bind with them," he said.

In other words, the drugs lose their ability to migrate to the brain to fight amyloid plaque. They also give up their targeted specificity against amyloid, Shoichet said. "They end up inhibiting everything -- any protein that sees them will be sequestered by them," he said. This molecular clumping process is largely inevitable, Shoichet added.

His advice to neuroscientists investigating these agents as potential Alzheimer's therapies: "They should stop."

Another expert agreed.

David Lynn is a Howard Hughes Institute investigator and professor of biological chemistry at Emory University in Atlanta. "I think that Brian's paper argues that [scientists] have been missing the boat here," he said. "It's not clear that you are ever going to get the concentrations that you need of these agents at the right site to be able to have any therapeutic intervention."

On the level of basic chemistry, attacking Alzheimer's and other protein-clumping diseases by preventing amyloid from concentrating has "always been a long shot," Lynn said. That's because amyloid proteins are incredibly "sticky," chemically speaking.

"To find things that will competitively stick and stop them from assembling is theoretically hard to imagine," Lynn said. It was thought that individual molecules of amyloid inhibitors might do so, but the new finding -- that the molecules inevitably bind together in a more impractical mass -- renders them therapeutically useless.

But other avenues of Alzheimer's research remain promising, Lynn said.

"There are certainly other strategies that have potential," he noted, including antibody-focused strategies aimed at eliminating plaques, or treatments focused on easing the downstream effects of amyloid buildup.

Both scientists stressed that it's still not certain whether protein plaques even cause Alzheimer's and other brain diseases, or whether they are merely byproducts of the disease process. "That's really another open area of research," Shoichet said.

"The problem with these diseases is that it is such a moving target," Lynn said. "And so, different people are looking at different things."

More information

There's much more on Alzheimer's disease at the Alzheimer's Association  .

MONDAY, Jan. 28 (HealthDay News) -- People who are physically active in their free time may be biologically younger than couch potatoes, a new British study suggests.

"A sedentary lifestyle increases the propensity to aging-related diseases and premature death. Inactivity may diminish life expectancy not only by predisposing to aging-related diseases, but also because it may influence the aging process itself," study author Lynn F. Cherkas, of King's College London, said in a prepared statement.

The researchers looked at the physical activity levels, smoking habits and socioeconomic status of 2,401 white twins. The researchers also collected DNA samples from participants, and examined the length of telomeres-repeated sequences at the end of chromosomes in white blood cells (leukocytes). Leukocyte telomeres shorten over time and may serve as a marker of a person's biological age.

Overall, the study participants had an average telomere loss of 21 nucleotides (structural units) per year. But those who were more active in their leisure time had longer leukocyte telomeres than those who were less active.

"Such a relationship between leukocyte telomere length and physical activity remained significant after adjustment for body-mass index, smoking, socioeconomic status and physical activity at work," the authors wrote.

"The mean difference in leukocyte telomere length between the most active [who performed an average of 199 minutes of physical activity per week] and least active [16 minutes of physical activity per week] subjects was 200 nucleotides, which means that the most active subjects had telomeres the same length as sedentary individuals up to 10 years younger, on average."

Oxidative stress damage caused to cells by exposure to oxygen and inflammation may be a factor contributing to shorter telomere length in sedentary people. Stress has also been linked to telomere length. Exercise may reduce stress and its effect on telomeres and the aging process, the study authors suggested.

"The U.S. guidelines recommend that 30 minutes of moderate-intensity physical activity at least five days a week can have significant health benefits," they wrote. "Our results underscore the vital importance of these guidelines. They show that adults who partake in regular physical activity are biologically younger than sedentary individuals. This conclusion provides a powerful message that could be used by clinicians to promote the potential anti-aging effect of regular exercise."

But more research is needed to confirm a direct link between physical activity and aging, the study added.

"Persons who exercise are different from sedentary persons in many ways, and although certain variables were adjusted for in this analysis, many additional factors could be responsible for the biological differences between active and sedentary persons, a situation referred to by epidemiologists as residual confounding," Dr. Jack M. Guralnik, of the U.S. National Institute on Aging, wrote in an accompanying editorial.

"Nevertheless, this article serves as one of many pieces of evidence that telomere length might be targeted in studying aging outcomes," he added.

The study was published in the Jan. 28 issue of the Archives of Internal Medicine.

More information

The U.S. Centers for Disease Control and Prevention has more about physical activity.

FRIDAY, Jan. 25 (HealthDay News) -- Antioxidants such as vitamin E and lutein could lower a woman's risk of sight-robbing cataracts, new research suggests.

The new observational study included more than 35,000 women aged 45 and older.

"The data suggests that those people who consumed diets higher in lutein/zeaxanthin or total vitamin E may have a lower risks of cataracts," said lead author William G. Christen, an epidemiologist at Brigham and Women's Hospital and Harvard Medical School, Boston.

Participants who consumed the largest amounts of lutein/zeaxanthin -- found in many vegetables -- had an 18 percent lower risk of developing cataracts than the group who consumed the least. The group who consumed the most vitamin E from both food and supplements had a 14 percent lower risk.

The study, published in the January issue of Archives of Ophthalmology, found that vitamin E obtained from food alone was not enough to reduce the risk significantly.

The lutein/zeaxanthin combination is most abundantly found in spinach, broccoli, kale, eggs, corn, and peas, Christen explained. He added, however, that it's too soon to be making specific food recommendations. Supplement manufacturers have recently added lutein to multivitamins, but a clinical trial is needed to determine a definite benefit from the compound, Christen explained.

Cataracts, a clouding of the eye's lens, afflicts many elderly adults. In fact, by age 80, more than half the population will have developed cataracts, according to the U.S. National Eye Institute (NEI). Cataracts can reduce the sharpness of vision or add a brownish tint to vision. According to the institute, smoking, alcohol use, diabetes and prolonged exposure to sunlight increase the risk of cataracts.

The new findings are based on a follow-up of female health professionals who participated in the multi-faceted Women's Health Study. At the beginning of the study, data was collected on the amount of lutein/zeaxanthin and vitamin E in each participant's diet, including their history of supplement use. Medical records were checked to verify the self-reports of cataracts from the more than 2,000 women who said they had developed cataracts.

The new study doesn't claim that lutein/zeaxanthin can prevent cataracts, only that it seems that it may delay their formation, the researchers stressed.

How might the nutrients ease or slow cataracts? Lutein/zeaxanthin are pigments, so they might "absorb harmful radiation coming into the eye from UV radiation," Christen speculated. "They may act as antioxidants as well," preventing cellular damage thought to be caused by free radicals.

Other studies, conducted in both men and women, have looked at the impact of lutein/zeaxanthin and/or vitamin E on cataracts, Christen said. But he said the new 10-year study is one of the longest so far. That's important, he said, because cataracts develop over time. "It appears that we are coming to a critical point where the data are strong enough to suggest a need for a clinical trial" looking at the antioxidants' potential impact on eye health, Christen said.

For its part, the NEI is currently is recruiting subjects from 50 to 85 years of age for a clinical trial on the ability of lutein/zeaxanthin and another antioxidant nutrient, fish oil, to reduce age-related cataracts and macular degeneration. Dr. Emily Y. Chew is leading that study, which she said will be a randomized, controlled trial looking at whether lutein/zeaxanthin, fish oil or a combination of lutein/zeaxanthin plus fish oil are effective.

Chew praised Christen's work as being "another piece of the puzzle that looks toward lutein being helpful." However, while lutein may appear protective in observational studies, that may not pan out in a stricter randomized trial, she said.

John J. McNeil, an Australian epidemiologist who has studied vitamin E and cataracts, agreed that a randomized clinical trial would be more reliable because "observational studies involving nutrients have a mixed record of reliability -- mainly because dietary patterns are so easily confounded by other aspects of lifestyle."

Several randomized clinical studies on vitamin E and cataracts -- including one of his own -- have had disappointing results, added McNeil, who heads the department of epidemiology and preventative medicine at Monash University in Melbourne.

Dr. Richard Bensinger, a spokesman for the American Academy of Ophthalmology, said he regards Christen's findings as "soft data," since it "wasn't designed to control for all the variables in diet and women."

For example, he said the study could not monitor the women's previous intake of food. That means that the researchers had to make assumptions about the amount of carotinoids in specific foods, although they can vary greatly based on how and where they were cultivated, he said.

More information

There's more on cataracts at the U.S. National Eye Institute.