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Caloric Restriction Extends Lifespan in Primates

A 20-year study in adult rhesus monkeys has shown that caloric restriction (CR) in these primates can extend healthy lifespan. At the end of the study, 37 percent of the control group had died of age-related causes, while only 13 percent of the CR group had. This finding means that the control monkeys experienced a death rate from age-related conditions such as diabetes, cancer, cardiovascular disease, and brain atrophy almost three times that of the CR group. Previous studies with yeast, worms, flies, and rodents have suggested that this kind of caloric restriction–a reduction of about 30 percent, and very different from malnutrition–can lead to such health benefits in some mammals, but given the many parallels between rhesus monkeys and humans, this study suggests that these benefits might occur in humans as well. "We have been able to show that caloric restriction can slow the aging process in a primate species," said Dr. Richard Weindruch, senior author of the study. "We observed that caloric restriction reduced the risk of developing an age-related disease by a factor of three and increased survival." The incidence of cancerous tumors and cardiovascular disease in animals on a restricted diet was less than half that seen in animals permitted to eat freely. Remarkably, while diabetes or impaired glucose regulation is common in monkeys that can eat all they want, it has yet to be observed in any animal on a restricted diet. "So far, we've seen the complete prevention of diabetes," said Dr. Weindruch. Furthermore, he noted, "The atrophy or loss of brain mass known to occur with aging is significantly attenuated in several regions of the brain. That's a completely new observation." The results of this study were published in the July 10 issue of Science.

A Molecular Link Between Obesity and Type 2 Diabetes Discovered

Although obesity is a major risk factor for type 2 diabetes, the factors linking these disorders are not well defined. Now, scientists at Monash University in Australia, and collaborating institutions, have obtained evidence for a molecular link between the two conditions. In a mouse model, the researchers have shown that a novel protein (pigment epithelium-derived factor or PEDF) released by fat cells triggers a chain of events and interactions that lead to the development of type 2 diabetes. "When PEDF is released into the bloodstream, it causes the muscle and liver to become desensitized to insulin. The pancreas then produces more insulin to counteract these negative effects," said Dr. Matthew Watt, senior author of the study. “This insulin release causes the pancreas to become overworked, eventually slowing or stopping insulin release from the pancreas, leading to type 2 diabetes. Our research was able to show that increasing PEDF not only causes type 2 diabetes-like complications but that blocking PEDF reverses these effects. The body again returned to being insulin-sensitive and therefore did not need excess insulin to remain regulated," Dr. Watt continued. "Until now scientists knew there was a very clear pattern and had strong suspicions that a link existed between the two conditions, but our understanding of the chain of events that are caused by the release of PEDF shows a causal link," Dr. Watt said. The results of this work were published in the July 8 issue of Cell Metabolism. [Press release] [Cell Metabolism abstract]

Easter Island Compound Extends Lifespan of Older Mice

In a multi-center study, scientists have shown that a compound first discovered in the soil of Easter Island can extend the lifespan of older mice. The compound is rapamycin, named from the Polynesian for the island, Rapa Nui. Discovered in the 1970s, rapamycin was first noted for its anti-fungal properties and later was used to prevent organ rejection in transplant patients. It is also used in stents, which are implanted in patients during angioplasty to keep coronary arteries open. It is in clinical trials for the treatment of cancer. In the current work, when rapamycin was added to the diets of older, genetically diverse mice (at an age equivalent to 60 years in humans), it extended lifespan by 28 to 38 percent. In human terms, this would be greater than the predicted increase in extra years of life if cancer and heart disease were both cured and prevented. "I've been in aging research for 35 years and there have been many so-called 'anti-aging' interventions over those years that were never successful," said Dr. Arlan G. Richardson, director of the Barshop Institute for Longevity and Aging Studies, and not involved in the study. "I never thought we would find an anti-aging pill for people in my lifetime; however, rapamycin shows a great deal of promise to do just that." "We believe this is the first convincing evidence that the aging process can be slowed and lifespan can be extended by a drug therapy starting at an advanced age," said Dr. Randy Strong, a lead author of the study. Aging researchers currently acknowledge only two life-extending interventions in mammals: calorie restriction and genetic manipulation. Rapamycin appears to partially shut down the same molecular pathway as restricting food intake or reducing growth factors.

Two Genes Associated with Mole Number and Melanoma Risk

Researchers from the Queensland Institute of Medical Research in Australia, and collaborators, have shown that variants in two genes (MTAP and PLA2G6) are associated with an increased number of moles and with an increased risk of melanoma, the deadliest form of skin cancer. "These are the first genes found to increase melanoma risk by influencing the number of moles a person has," explained Dr. Nick Hayward, a lead author of the study. "This finding improves our understanding of the genetics of melanoma and therefore the molecular pathways that lead to its development.” He noted that “it has long been known that having a large number of moles is the biggest risk factor. Therefore we predicted we would find genes linking moles and melanoma. We now have conclusive genetic evidence that having a large number of moles increases an individual's risk of developing melanoma." The study found that having an associated variant in one of the two genes increased the risk of melanoma by 25 percent, while having associated variants in both genes doubled the risk. Australia has the highest incidence of melanoma in the world with more than 10,000 new cases and 1,000 people dying from the disease every year. Queensland has the highest incidence of any state in Australia with seven Queenslanders diagnosed with melanoma every day. More than one in 20 Queenslanders is expected to develop melanoma during his or her lifetime. The new research was reported online in Nature Genetics on July 5. [Press release] [Nature Genetics abstract]

Prostate Cancer Homing Molecule Could Carry Imaging Agents and Therapeutics

Researchers at Purdue University and Endocyte, Inc., have synthesized a molecule that selectively targets prostate cancer cells and penetrates them. The researchers have designed the molecule so that imaging agents or therapeutic agents can be carried with it as cargo. The molecular “homing device” could improve detection and allow for the first targeted treatment of the disease, the researchers believe. "Currently none of the drugs available to treat prostate cancer are targeted, which means they go everywhere in the body as opposed to only the tumor, and so are quite toxic for the patient," said Dr. Philip Low, senior author of two papers describing the new research in the June 1 edition of Molecular Pharmaceutics. "By being able to target only the cancer cells, we could eliminate toxic side effects of treatments. In addition, the ability to target only the cancer cells can greatly improve imaging of the cancer to diagnose the disease, [and to] determine if it has spread or is responding to treatment." Prostate cancer is the most common cancer, other than skin cancers, and is the second leading cause of cancer death in American men, according to the American Cancer Society. It is estimated that about 192,280 new cases will be diagnosed and 27,360 men will die of prostate cancer in the United States this year. The new synthetic molecule attaches to prostate-specific membrane antigen (PSMA), a protein that is found on the membranes of more than 90 percent of all prostate cancers. It also is found on the blood vessels of most solid tumors and thus could also provide a way to cut off the tumor blood supply, Dr. Low said. "A lot of new drugs are being designed to destroy the vasculature of solid tumors, and, if they could be linked to this new targeting molecule, we could have a two-pronged attack for prostate cancer," he said.

Gene Region Linked to Perfect Pitch

Researchers at the University of California-San Francisco (UCSF) have found evidence that a particular gene region on chromosome 8 is linked to the phenomenon of perfect pitch (also known as absolute pitch), at least in people of European ancestry. The finding, part of a larger examination of families of various ancestries (Europeans, Ashkenazi Jews, Indians, and East Asians) is said to be the first significant genetic evidence for a role of genes in perfect pitch. Perfect pitch is the rare ability to instantaneously recognize and label tones with their musical note names without using a reference pitch for comparison. It is likely, the researchers said, that multiple genes are involved in all cases of perfect pitch and that different genes could be associated with perfect pitch in those from different ethnic backgrounds. "Perfect pitch is a window into the way in which multiple genes and environmental factors influence cognitive or behavioral traits," said Dr. Jane Gitschier, the senior author of the study. The UCSF research team has learned over the last decade that both influences contribute to perfect pitch. "What's exciting now," Dr. Gitschier said, "is that we now have made the first foray into teasing out the genes that may be involved." This work was published online on July 2 in the American Journal of Human Genetics. [Press release] [AJHG abstract]

Comas in Locusts Offer Clues to Human Migraine and Stroke

Neural spreading depression (SD), a phenomenon in which neurons shut down, is associated with important human CNS pathologies, including migraine and stroke. Locusts undergo SD-like events when exposed to extremer conditions such as high temperature or lack of oxygen. The insects essentially go into a coma and emerge from it after the stress is removed. Now, a Queen’s University-Canada research team has shown that the ability of the locusts to resist entering the coma, and the speed of their recovery, can be manipulated using drugs that target one of the cellular signaling pathways in the brain, i.e., the nitric oxide/cyclic guanosine monophosphate/protein kinase G (NO/cGMP/PKG) pathway. "This suggests that similar treatments in humans might be able to modify the thresholds or severity of migraine and stroke," said Gary Armstrong, lead author of the report. "What particularly excites me is that in one of our locust models, inhibition of the targeted pathway completely suppresses the brain disturbance in 70 percent of animals," added Dr. Mel Robertson, senior author of the study. Noting that it is hard to drown an insect, due to its ability to remain safely in a coma under water for several hours, Mr. Armstrong said, "It's intriguing that human neural problems may share their mechanistic roots with the process insects use to survive flash floods." This research was reported in the June issue of the Journal of Neuroscience. [Press release] [Journal of Neuroscience abstract]

Compound Stops Diabetic Retinopathy in Experimental Systems

Researchers at the University of Oklahoma Health Sciences Center and the University of Nebraska Medical Center have found evidence that a natural angiogenic inhibitor known as plasminogen kringle 5 (K5) can be used to stop diabetic retinopathy, one of the leading causes of blindness in the United States. Diabetic retinopathy is caused by changes in blood vessels of the retina, the light-sensitive tissue at the back of the eye. In some people with diabetic retinopathy, blood vessels may swell and leak fluid. In other people, abnormal new blood vessels grow on the surface of the retina. Over time, diabetic retinopathy can worsen and cause some vision loss or blindness. The researchers found that this inflammation and leakage is caused by an imbalance of two systems in the eye. To restore this balance, they delivered K5 to cells using nanoparticle technology. In rat models, the treatment stopped the leakage, blocked inflammation, and kept unwanted blood vessels from growing. “There is no good treatment for retinopathy, which is why we are so excited about this work. This opens an entirely new area for pharmaceutical companies to target,” said Dr. Jay Ma, the senior author of the study. The discovery of K5’s function in inflammation and blood vessel formation related to eye disease means scientists may now possibly be able to develop new therapies, including eye drops, to stop diabetic retinopathy, a disease which affects as many as five million Americans with type 1 or type 2 diabetes. The researchers are now testing K5’s uses for cancer and age-related macular degeneration. The research results were reported online on June 2 in Diabetes. [Press release] [Diabetes abstract]

Interferon-Alpha May Delay Full Onset of Type 1 Diabetes

Results of a phase 2 trial indicate that a low dose of oral interferon-alpha may, for a period, preserve beta cell function in newly diagnosed type 1 diabetes (formerly juvenile diabetes). "It shows a strong trend in preserving insulin-producing beta cell function that is significantly better than placebo," said Dr. Staley Brod, principal investigator of the trial, which includes the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). "It can extend the 'honeymoon phase' of the disease, allowing the body to still produce insulin from beta cells, which correlates with decreased complication rates." A honeymoon phase sometimes occurs just after diagnosis as the body tries to rebound. Many patients experience a period when their need for insulin becomes minimal, control of blood sugar improves and beta cells partially recover. If the pancreas is still able to function, the highs and lows experienced by taking manufactured insulin can be decreased. The results of the phase 2 trial were published in the July issue of Diabetes Care. [Press release] [Diabetes Care abstract]

Desert Rhubarb Is “Self-Irrigating” Plant

Researchers from the University of Haifa-Oranim have discovered that the desert rhubarb in the mountains of Israel’s Negev desert is able to harvest 16 times as much water as other plants in the arid area that receives only 75 mm of rainfall annually. The scientists determined that the rhubarb achieves this feat by having unusually broad leaves that have ridged surfaces much resembling a mountain range. These ridged surfaces funnel water down to the ground surrounding the plant’s single deep root and serve essentially as a “self-watering” system. "We know of no other plant in the deserts of the world that functions in this manner," the researchers concluded. Most desert plants have very small leaves in order to minimize moisture loss and survive on the little rain water that penetrates the ground in their immediate area. In addition to the rhubarb’s harvesting much more water than small-leaved desert plants, experiments showed that water that funneled down the rhubarb’s leaves penetrated as deep as 10 cm into the ground, whereas water that simply fell on the ground penetrated only 1 cm deep. The image shows the desert rhubarb and is credited to Professor Gidi Ne'eman, University of Haifa. [Press release]

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