Researcher studies protein's role in aging

With time, the amino acid known as asparagine will eventually degrade. Long considered a type of protein “damage,” the phenomenon has come to be accepted as yet another part of aging: our hair turns gray, our joints begin to ache, and our asparagine turns into isoaspartic acid.

The surprising thing about this change is that it forces the protein’s backbone to follow a new track, just like a railroad switch sends a train on an entirely different journey. “This is exceptionally rare,” said chemistry and associate professor Sunny Zhou, who recently received a $1 million grant from the National Institutes of Health to study the etiologic role of isoaspartic acid, or isoAsp, in aging and disease. It’s research that could dramatically change how doctors treat diseases such as Alzheimer’s, which significantly elevates patients’ isoAsp levels.

According to Zhou, the rate at which isoAsp forms depends on the sequence of  in the protein. If asparagine sits next to the amino acid proline, it will take a long time to degrade. If it’s next to glycine, on the other hand, it may take just half a day. Luckily, there’s an . The enzyme “protein isoaspartate ,” or PIMT, can rectify the damage.

The degradation process that leads to isoAsp happens in virtually all cells and PIMT is present in almost all animal systems except baker’s yeast; how regulate isoAsp remains a mystery. Additionally, animal studies have shown that eliminating PIMT from the body does reduce life expectancy—but not through aging. “IsoAsp levels in these animals increase,” said Zhou. “But only twofold, not tenfold.” This suggests something else must be at play in the regulation process in other animals too, not just yeast.

IsoAsp has the same  as aspartic acid, making it extremely difficult to detect. At least it used to be. In previous research as a faculty fellow at Northeastern’s Barnett Institute of Chemical and Biological Analysis, Zhou helped develop a method for easily tracking it down.

Degradation cannot be prevented, he said, because it happens spontaneously. But if researchers found a way to repair the damage, their work could have a significant effect on the ability to treat age-related disease such as Alzheimer’s.

“If we can find the machinery that gets rid of isoaspartic faster, then we can somehow use a driver to boost that machinery,” Zhou said, noting that the damaged cells in an Alzheimer’s brain contain up 70 percent isoaspartic acid. “That’s the hope.”

New herbal supplement helps slim and trim without side effects, studies show

New herbal supplement helps slim and trim without side effects, studies show

Study participants who took a new herbal supplement, while also exercising and controlling their food intake, had greater success in losing weight and slimming down than did those who didn’t take the supplement, report researchers at the University of California, Davis, and in India.

The researchers suggest that the supplement—made from extracts of a wild herb and a tropical fruit rind—may be a safe and effective aid for dealing with and obesity, which affect more than 60 percent of adults in the United States.

Two clinical trials involving the supplement were conducted at Alluri Sitarama Raju Academy of Medical Sciences in India. Results from both trials combined are reported in the June issue of the Journal of Medicinal Food, while results from just the second of the two trials appears in the May issue of the journal Obesity.

Data analysis and study communication was led by Judith Stern, distinguished professor of nutrition and internal medicine at UC Davis.

“The results from our study are promising, and we did not see significant side effects with this supplement extract,” Stern said. “This was a short-term study, and we don’t know what happens in the long run; along with a diet and exercise program, the results may be even greater,” she said.

Stern noted that study results indicate that the herbal supplement may cause these positive effects by interfering with the formation and storage of fatty compounds in the body.

The two studies included a total of 95 subjects, many of whom were considered obese according to their —a measurement based on a person’s weight and height and used to screen for weight categories that may lead to health problems.

During each clinical trial, participants in the test group received twice daily a 400-mg capsule containing the herbal mix. That mix was made from extracts of the aromatic annual plant Sphaeranthus indicus, a member of the aster and daisy family, and the rind of the tropical fruit Garcinia mangostana, commonly called mangosteen. Both plants have long been valued as having medicinal properties in Ayurvedic medicine—an ancient system of medicine that originated in India.

Participants in the control group for the two trials received placebo capsules rather than the herbal supplement. All participants in the study also were provided with three meals totaling 2,000 kcal per day, and each of the participants walked for 30 minutes five days per week.

At the end of each eight-week trial, the researchers found that participants who had taken the herbal supplement lost significantly more weight than did the control-group participants, who had not taken the supplement.

In the combined clinical outcomes reported in the Journal of Medicinal Food, the test-group participants with the supplement had lost an average of 5.2 kg (11 lbs. 7 oz.) by the end of eight weeks compared to the control group participants’ loss of an average of 1.5 kg (3 lbs. 5 oz.) The supplemented group also had an average decrease in waist circumference of 11.9 cm (about 4.75 inches) compared to the control group’s average decrease in waist circumference of 6 cm (about 2.5 inches).

In the clinical trial published in the journal Obesity, participants taking the supplement lost an average of 5.1 kg (11 lbs. 3 oz.) compared to the control group’s loss of an average of 1.3 kg (2 lbs. 15 oz.). The supplemented group also had an average decrease in waist circumference of 11.8 cm (4.5 inches) compared to the control group’s average decrease in waist circumference of 6.4 cm (about 2.5 inches).

The researchers also noted that in both clinical trials, the study participants receiving the herbal supplement experienced significant reduction in their blood levels of cholesterol and triglycerides.

Consumption of the  did not to appear to be linked to any negative health effects in any either clinical study, the researchers said.

 

More about weight loss recent news:

The new weight loss drug lorcaserin (Belviq) appears to improve blood sugar control in nondiabetic, overweight individuals, independent of the amount of weight they lose, a new study finds. The results will be presented Saturday at The Endocrine Society’s 95th Annual Meeting in San Francisco.

Lorcaserin activates a (5HT2C) in the brain believed to decrease appetite and promote a sense of fullness, thus encouraging decreased , said the study’s principal investigator, Louis Aronne, MD, professor of clinical medicine at Weill Cornell Medical College, New York City.

“This analysis supports the possible role that the drug’s serotonin receptor activation may play in regulating glucose [blood sugar] metabolism,” Aronne said.

The U.S. approved lorcaserin last June as an add-on treatment to diet and exercise for long-term weight management in adults who are obese (, or BMI, greater than 30 kg/m2), or overweight (BMI of 27 or greater) with at least one weight-related health complication.

Aronne’s study was a pooled analysis of two previously published clinical trials that together included more than 6,300 overweight or obese, nondiabetic patients. These trials compared the effects of lifestyle changes—diet and exercise—combined with either lorcaserin treatment or a placebo ().

The new study received funding from San Diego-based Arena Pharmaceuticals, the maker of lorcaserin, and from Eisai in Woodcliff Lake, N.J.

As a group, the 3,195 patients treated with lorcaserin tablets lost twice as much weight after one year of treatment and lifestyle changes than the 3,185 patients in the  did: an average of 12.8 pounds versus 5.6 pounds, the study authors reported. However, even when lorcaserin-treated patients and placebo-treated patients lost the same amount of weight, those receiving lorcaserin had a greater average decrease (improvement) in their  level than the other group did, Aronne said. Hemoglobin A1c is a measure of long-term glycemic (blood sugar) control.

“More than just weight loss alone may explain the significant improvement in glycemic control associated with lorcaserin,” Aronne said.

Fasting blood sugar levels also were better after one year in the lorcaserin group, which had an average decrease since the study started of 0.23 milligrams per deciliter (mg/dL), according to the abstract. In the placebo group, fasting blood sugar levels rose 0.60 mg/dL in the same period.

In a separate study not included in this analysis, lorcaserin also demonstrated improved blood glucose measures in patients with type 2 diabetes, Aronne said.

The two earlier studies included in the new analysis were the BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) Study and BLOSSOM (Behavioral modification and Lorcaserin Second Study for Overweight and Obesity Management). The pooled data confirmed the independent findings of BLOOM and BLOSSOM, Aronne said.

Helping to restore balance after inner ear disorder

Many disorders of the inner hear which affect both hearing and balance can be hugely debilitating and are currently largely incurable. Cochlear implants have been used for many years to replace lost hearing resulting from inner ear damage. However, to date, there has not been an analogous treatment for balance disorders resulting from inner ear disease. One potential new treatment is an implantable vestibular prosthesis which would directly activate the vestibular nerve by electrical stimulation. This prosthetic treatment is tested in a new study by Christopher Phillips and his colleagues from the University of Washington in Seattle, USA. Their findings are published in the Springer journalExperimental Brain Research.

Meniere’s disease is a disorder of the inner ear that can affect hearing and balance to varying degrees. The characteristic symptoms are episodes of vertigo, tinnitus, a feeling of pressure in the  and hearing loss which tends to worsen as time goes on. Although there is medication which can help once an attack is underway, there is currently no long-term therapy which can resolve the disease completely.

Phillips and his colleagues have developed a vestibular prosthesis which delivers electrical stimulation to the fluid inside the semi-circular canals of the ear. In effect, the stimulation of the fluid makes the brain believe that the body is moving or swaying in a certain direction. This then causes a compensatory postural reflex to stabilize the posture thereby helping to restore balance.

For their study, this prosthesis was inserted into the ears of four subjects all suffering from long-term Meniere’s disease and differing degrees of hearing loss which was resistant to other . After a full evaluation of each participant’s vestibular function, their eye function was measured in response to electrical stimulation along with their postural response both with their eyes open and closed.

The researchers found that  of the fluid in the semicircular canals of the affected ear did result in a change in posture, the direction of which was dependent on which ear was stimulated. However, each subject had different sway responses to the stimulation given. The authors believe this could be caused by small differences in the location of the electrode between subjects. Thus fine tuning and individual calibration for each electrode implant would be required for it to be effective.

Overall the results illustrate that this type of prosthesis may eventually be a possible treatment for balance issues caused by Meniere’s disease. However, there are a large number of matters which would need resolving before it is ready for use. The lack of consistency in direction and magnitude of sway response would require further study to ensure that any prosthesis developed could give reliable results for different individuals.

The authors conclude: “Taken together, our findings support the feasibility of a vestibular  for the control of balance and illustrate new challenges for the development of this technology. This study is a first step in that direction.”