Chemical concoctions can smooth over wrinkles and hide those pesky grays, but what about the signs of aging that aren’t so easy to fix, such as losing muscle mass? Cutting calories early could help, say University of Florida researchers who studied the phenomenon in rats.A restricted-calorie diet, when started in early adulthood, seems to stymie a mitochondrial mishap that may contribute to muscle loss in aging adults, the researchers reported recently in the journal PLoS One.

In rats, the scientists found pockets of excess iron in muscle cell mitochondria, the tiny power plants found in every cell. The excess iron affects the chemistry inside the mitochondria, sparking the formation of harmful free radicals that can lead a mitochondrion straight to the emergency exit, said Christiaan Leeuwenburgh, a UF professor of aging in the UF College of Medicine and the Institute on Aging. Leeuwenburgh was the senior author of the study and of a related report published online this month in Aging Cell that details the damage done by excess iron in mitochondria.

“We become less efficient at an old age and we need to understand why this is,” Leeuwenburgh said. “One thing, maybe, is the accumulation of redox-active metals in cells. If the mitochondria become unhappy or are ready to kick the bucket, they have proteins in the inner and outer membranes that they can open up and commit suicide. They’re tricky beasts.”

The suicidal mitochondria can damage the rest of the muscle cell, leading to cell death and perhaps to muscle wasting, a big problem for adults as they reach their mid-70s, Leeuwenburgh added.

“Muscle is critical for your overall well-being,” Leeuwenburgh said. “As you walk, muscle functions partly as a pump to keep your blood going. Muscle is an incredible source of reserves.”

The researchers found increasing amounts of iron in the muscle cells of aging rats fed a typical unrestricted diet. The older the rats got, the more iron accumulated in the mitochondria and the more damage was done to its RNA and DNA. Rats of the same ages that were kept on a calorie-restricted diet — about 60 percent of the food typically ingested — seemed to maintain more normal iron levels in mitochondria, the researchers reported.

“The novel thing here is that iron is accumulating in places it does not normally accumulate,” said Mitch Knutson, a UF assistant professor of food science and human nutrition and a study co-author. “Such iron accumulation in muscle was quite unexpected. This may be of concern because more people are genetically predisposed to developing iron overload than we originally thought.”

The problem occurs when metals such as iron accumulate in the mitochondria and react with oxygen. Iron can change the chemical structure of oxygen, triggering its metamorphosis into a free radical, an unstable atom that can upset the delicate balance inside the mitochondria. The result? Leeuwenburgh describes it sort of like internal rust.

“Not all free radicals are harmful,” Leeuwenburgh said. “To just use antioxidants to neutralize all free radicals is a huge misconception because some radicals are helpful. You just need to try and target very specific free radicals that form in specific parts of the body.”

Researchers don’t know exactly what causes iron to accumulate in mitochondria in aging animals, but a breakdown in how iron is transported through cells could be one reason why, Leeuwenburgh said. Understanding how caloric restriction limits the problem in rats could help researchers better understand how to combat it, he added.

Russell T. Hepple, an associate professor of kinesiology and medicine at the University of Calgary in Canada, said the findings are another step forward in linking iron to muscle cell death, but there are more questions researchers must answer.

“They’ve shown that apoptosis (cell death) goes up in aging muscle but where does that happen?” Hepple asked. “There are more than muscle cells in muscle. (For example) in older adults there are inflammatory cells.”

Source: University of Florida (http://news.ufl.edu/2008/09/16/iron-link/)

The most comprehensive-to-date genomic analysis of a cancer – the deadly brain tumor glioblastoma multiforme – shows previously unrecognized changes in genes and provides an overall view of the missteps in the pathways that govern the growth and behavior of cells, said members of The Cancer Genome Atlas Research Network in a report that appears online today in the journal Nature.

“This was a big thrust for the public project,” said Dr. Richard Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Center, a member of the network and a co-author of the paper. “This answers the big question about whether the cancer genome project is worthwhile. The results show that it is—definitely.” The BCM center, the Genome Sequencing Center at Washington University School of Medicine in St. Louis, Mo., and the Broad Institute of MIT and Harvard in Cambridge, Mass., led the effort that included many members from across the nation.

Analysis reveals important clues

This interim analysis of 91 tumors and 623 genes provides important clues about how the disease originates and progresses in cells and how it eludes the effects of potent anti-cancer drugs and radiation, said Dr. David Wheeler, associate professor in the Genome Sequencing Center and a co-author of the report. It could provide researchers with clues about how to treat the disease. The Baylor Human Genome Sequencing Center was a major component in the effort to sequence the genes and identify mutations and changes that affected the ways cells react.

“Studies like this show the breadth of mutation across many genes,” said Wheeler. “We can see the mutations in all the genes of each pathway that control growth, replication and death in the cancer cell. Researchers have never seen the whole landscape like this before, and it’s providing many new insights into strategies to diagnose and treat cancer.”

The ultimate goal of the project is to sequence the entire exome – that portion of the genetic blueprint that provides the code for proteins – of the tumor, said Wheeler. In fact, he said, the goal is to sequence genes in 500 brain cancer samples, but the network decided to publish preliminary results.

“When we pulled everything together with just 91 samples, the results were so interesting and important for treatment that we felt we should publish before the end of the project,” he said.

Glioblastoma is the most common primary brain tumor. Most people live approximately one year after diagnosis. Understanding this cancer could result in better forms of treatment.

Wider view of cell pathways

The analysis identified some genes known to cause cancer but whose role in glioblastoma had been previously underestimated, he said. For example, the genes ERBB2 (known to be implicated in breast and other cancers) and NF1 (neurofibromatosis gene 1 involved in a variety of tumors) were both found to be frequently mutated in this brain tumor. Other genes that previously had no known role in glioblastoma such as PIK3R1, a gene involved in regulating the metabolic actions of insulin were also found mutated in a variety of tumors.

In addition, the analysis gave scientists a wide view of how cell pathways are altered during the initiation and growth of glioblastoma.

“If we know what pathways are key to the formation of a tumor, we can design drugs to block those pathways,” said Wheeler. “In cancer, key pathways are co-opted to make the cell grow and divide in an uncontrolled fashion.”

For example, the TP53 pathway tells mutated cells to die in a process called apoptosis.

“It’s a fail-safe mechanism,” said Wheeler. “If a cell starts to become cancerous, p53 causes the cell to kill itself. If that pathway is knocked out, the cell avoids the fail-safe mechanism and can continue to divide.”

Other pathways involved in the sequencing effort are also disrupted to allow the cancer to grow, he said.

Funding for this work came from the National Institutes of Health.

Others who took part in the sequencing effort at BCM include Donna Muzny, Margaret Morgan, Steve Scherer, Aniko Sabo, Lynn Nazareth, Lora Lewis, Otis Hall, Yiming Zhu, Yanru Ren, Omar Alvi, Jiqiang Yao, Alicia Hawes, Shalini Jhangiani, Gerald Fowler, Anthony San Lucas, Christie Kovar, Andrew Cree, Huyen Dinh, Jireh Santibanez, Vandita Joshi, Manuel L. Gonzalez-Garay, Christopher A. Miller, Aleksandar Milosavljevic and Larry Donehower.

Other institutions involved in this work include the Dana-Farber Cancer Institute in Boston; Harvard Medical School and The Brigham and Women’s Hospital in Boston; Memorial Sloan-Kettering Cancer Center in New York; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore; the National Cancer Institute Center for Bioinformatics in Bethesda, Md; the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill; SRA International Inc., in Fairfax, Va.; HudsonAlpha Institute for Biotechnology in Huntsville, Ala.; Lawrence Berkeley National Laboratory in Berkeley, Calif., and the International Genomics Consortium in Phoenix, Ariz.

Source: Baylor College of Medicine (http://www.bcm.edu/news/item.cfm?newsID=1200)

A program to groom leaders for southern African nations is also producing South Dakota State University research that could add value to dairy products.

Researcher Rosemary Nyoka of Zimbabwe is finding that supplementing the diets of grazing dairy cows with dried distillers grains or fishmeal could increase the level of healthful fatty acids in milk and milk products such as cheese.

“With this potential to improve the healthful fatty acids, we are finding additional uses for distillers grains,” Nyoka said. “We are also trying to improve profitability for dairy farmers. We are hoping they will be able to sell these products at a premium.”

Nyoka, is working towards a Ph.D. in dairy science at SDSU and is also a Fellow of the Kellogg Southern Africa Leadership, or KSAL, Program.

Viwe Mtshontshi, senior program officer from AED, a Washington, D.C.-based organization that administers the KSAL program, said the organization is very pleased with level of support given by the faculty in the SDSU Dairy Science Department.

“Nyoka’s chosen area of research meets one of the Kellogg Foundation, Africa Program goals — addressing the challenge of food security in southern Africa,” Mtshontshi said.

Nyoka’s research is evaluating the extent to which dietary manipulations can improve the levels of healthful fatty acids in milk.

“I’m supplementing cows on pasture with fishmeal and distillers grains to see how much these high-fat diets will improve the concentrations of the healthful fatty acids in the milk and dairy products,” Nyoka said. “I will analyze to see how much fatty acid has been added to the milk through the diet, and then I’ll process the milk and analyze to see how much fatty acid has been added and retained in the cheese.”

Nyoka is monitoring healthful fatty acids called conjugated linoleic acids, or CLAs.

“These CLAs are known now to have anti-carcinogenic properties, as well as anti-arthritis and anti-obesity properties. They’ve also been known to improve bone formation,” Nyoka said. “In general, in an average American diet we are eating maybe 1 gram per day of these fatty acids, while the effective levels known so far are like 3.5 grams of the fatty acids. So we see that in general, people are not getting enough.”

CLAs are found mainly in products from ruminant animals such as milk and meat. Milk typically contains between 0.3 grams and 0.6 grams of CLAs per 100 grams of fat, Nyoka said. But on her trial diets, Nyoka’s SDSU cows produced milk with total CLAs ranging from 2.5 to 5 grams.

“I’m grazing the cows on an alfalfa pasture, and then they get half their daily requirements from a supplement which is either soybean-based, distillers grains-based or fishmeal-based,” Nyoka said.

The soybean-based supplement is the control, since dairy producers commonly use it. The fishmeal- and distillers grains-based diets are Nyoka’s areas of interest.

“Now with the ethanol plants we have a lot of distillers grains, and it has high fat content. Most of the fat in the distillers grains are the unsaturated fatty acids, which are the major precursors for the CLAs,” Nyoka said. “So we want to see how the distillers grains will compare to the fishmeal, as well as to the control diet.”

Nyoka is including cheese in her research because one of her interests is in finding alternative, high-value products that farmers in Zimbabwe can more easily transport to market from remote locations.

As a government dairy officer in Zimbabwe, Nyoka not only helps dairy farmers troubleshoot production issues, she also works with dairy manufacturers. That’s one reason she is studying at SDSU, one of the few dairy science departments in the United States that includes both dairy production and dairy manufacturing under one roof.

Professor Arnold Hippen, Nyoka’s adviser, said one advantage of the SDSU program is that it gives international students a more holistic view of the dairy industry — from the care of the animal to the finished dairy product — while emphasizing animal nutrition.

Vikram Mistry, head of the SDSU Dairy Science Department, said Nyoka is the second Ph.D. student to come through SDSU as a Kellogg Foundation scholar from Africa. SDSU graduate Gaolebale Mpapho has already returned to Botswana after earning her Ph.D.

“We have always talked about how important we are in the dairy education world in the United States,” Mistry said. “This program gives us the opportunity to have an impact beyond our borders.”

Source: South Dakota State University (”http://www3.sdstate.edu/SDSU/NewsDetail45702.cfm?ID=46,6612“)