Aging related Press Releases

PRESS RELEASE: Skin Aging Reversed In Mice By Blocking Action Of Single Protein

Maureen Martino — Tue, 04 Dec 2007 09:57:10 -0500

Skin Aging Reversed In Mice By Blocking Action Of Single Protein

Researchers at the Stanford University School of Medicine have reversed the effects of aging on the skin of mice, at least for a short period, by blocking the action of a single critical protein.

The work could one day be useful in helping older people heal from an injury as quickly as they did when they were younger, said senior author Howard Chang, MD, PhD, assistant professor of dermatology. However, Chang and his colleagues warned their finding will likely be useful in short-term therapies in older people but not as a potential fountain of youth.

The work backs up the theory that aging is the result of specific genetic changes rather than accumulated wear and tear, Chang said. What's more, those genetic changes can be reversed even late in life.

"The implication is that the aging process is plastic and potentially amenable to intervention," Chang said. The results will be published in the Dec. 15 issue of the journal Genes and Development.

The work came about thanks to existing data from experiments using microarrays, which detect the activity of all genes in a cell. In past experiments, researchers have found a large number of diverse genes that become either more active or less active in older people.

Chang and graduate student Adam Adler, the study's first author, searched through this existing data to see if those age-related genes had anything in common. It turned out that their activity gets dialed up or down with the help of the protein called NF-kappa-B.

Chang said people had long known that NF-kappa-B winds its way into a cell's nucleus to control which genes were active. What they didn't know is that many of those genes regulated by the protein have a role in aging.

Chang and Adler tested whether blocking the activity of NF-kappa-B in the skin of older mice for two weeks had a youthful effect. "We found a pretty striking reversal to that of the young skin," Chang said.

First they looked at the genetic changes resulting from blocking NF-kappa-B. After two weeks, the skin of 2-year-old mice had the same genes active as cells in the skin of newborn mice-a striking difference when compared with the skin of a normal 2-year-old mouse. The skin looked more youthful too. It was thicker and more cells appeared to be dividing, much like the skin of a younger mouse.

Chang and Adler caution that their findings aren't likely to be the source of the long-sought fountain of youth. That's because they don't know if the rejuvenating effects of NF-kappa-B are long-lasting. Also, the protein has roles in cancer, the immune system and a range of other functions throughout the body. Suppressing the protein on a long-term basis could very well result in cancers or other diseases that undermine its otherwise youthful effect.

"You might get a longer lifespan but at the expense of something else," Chang said.

Instead, the researchers believe their work could point to a way of helping older people heal more quickly after surgery or boost organ function during illness. These short-term applications aren't as likely to risk side effects that could accompany blocking such a critical protein.

The work was supported by grants from the American Cancer Society, the National Institutes of Health, the National Cancer Institute and the California Breast Cancer Research Program.

Other Stanford researchers who participated in the work are graduate student Tiara Kawahara and Jennifer Zhang, PhD, who was a postdoctoral scholar.

PRESS RELEASE: Drug Commonly Used to Treat Bi-Polar Disoreder Dramatically Increases Lifespan in Nematode Worms

Maureen Martino — Thu, 01 Nov 2007 11:57:25 -0400

Drug Commonly Used to Treat Bi-Polar Disoreder Dramatically Increases Lifespan in Nematode Worms

Nematode worms treated with lithium show a 46 percent increase in lifespan, raising the tantalizing question of whether humans taking the mood affecting drug are also taking an anti-aging medication. Results of the Buck Institute study, led by faculty member Gordon J. Lithgow, PhD, are currently published online in the Journal of Biological Chemistry.

Lithium has been used to treat mood affective disorders, including bipolar disease for decades. While the drug has been shown to protect neurons, the underlying mechanism of its therapeutic action is not understood. In humans, lithium’s therapeutic range is very limited and the drug has serious side effects. The research provides a novel genetic approach to understanding how lithium works and highlights the utility of using the nematode C. elegans as a research subject in the field of “pharmacogenetics”. Pharmocogenetics involves the study of genetic factors that influence an organism’s reaction to a drug.

In the study, scientists discovered that longevity was increased in the worms when the lithium “turned down” the activity of a gene that modulates the basic structure of chromosomes.

Lithgow believes that lithium impacts many genes. “Understanding the genetic impact of lithium may allow us to engineer a therapy that has the same lifespan extending benefits,” said Lithgow. “One of the larger questions is whether the lifespan extending benefits of the drug are directly related to the fact that lithium protects neurons.” The process of normal aging in humans is intrinsically linked to the onset of neurodegenerative disease. However, the cellular changes and events due to aging that impact neurodegeneration are not yet understood said Lithgow. Studies involving compounds such as lithium could provide breakthroughs in the attempt to understand the biomedical link between aging and disease. Lithgow and his lab are now surveying tens of thousands of compounds for affects on aging.

The study highlights the efficacy of using C. elegans as a new way of studying drug toxicity and genetic impacts of compounds currently in drug development or already in use in humans. “The use of simple model organisms with well developed genetic tools can speed the identification of molecular targets,” said Lithgow. “This could facilitate the development of improved therapies for diseases.”

Others involved in the study include Simon Melov and Maithili C. Vantipalli, also of the Buck Institute; Gawain McColl, the lead author, formerly of the Buck Institute, now at the Mental Health Research Institute of Victoria, Australia; along with David W. Killilea of Children’s Hospital Oakland Research Institute, Oakland, CA and Alan E. Hubbard, University of California, Berkeley. G.M was supported by the American Federation for Aging Research. S.M was supported by the Ellison Medical Research Foundation, and NIH AG24385 and AG18679. G.J.L is supported by NIH AG21069, AG22868, NS050789-01, the Ellison Medical Research Foundation, the Glenn Foundation for Medical Research and the Herbert Simon Family Medical Foundation. Gene expression studies were facilitated by a Nathan Shock award P30AG025708. All other nematode strains were obtained from the Caenorhabditis Genetics Center, funded by the National Institutes of Health National Center for Research Resources.

The paper can be accessed at http://www.jbc.org/cgi/content/abstract/M705028200v1

The Buck Institute is an independent non-profit organization dedicated to extending the healthspan, the healthy years of each individual’s life. The National Institute on Aging designated the Buck a Nathan Shock Center of Excellence in the Biology of Aging, one of just five centers in the country. Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer’s and Parkinson’s disease, cancer, stroke, and arthritis. Collaborative research at the Institute is supported by genomics, proteomics and bioinformatics technology.

PRESS RELEASE: Genes That Both Extend Life And Protect Against Cancer Identified

Maureen Martino — Tue, 16 Oct 2007 10:24:03 -0400

Genes That Both Extend Life And Protect Against Cancer Identified

A person is 100 times more likely to get cancer at age 65 than at age 35. But new research reported today in the journal "Nature Genetics" identifies naturally occurring processes that allow many genes to both slow aging and protect against cancer in the much-studied C. elegans roundworm.

Many of the worm genes have counterparts in humans, suggesting that new drugs may some day ensure a long, cancer-free life. The new research and a related study the scientists reported in "Science" last year indicate that cellular changes leading to longevity antagonize tumor cell growth.

The studies are by scientists at the University of California, San Francisco, who say the research also underscores the deep evolutionary connection between lifespan and cancer.

The worms, known formally as Caenorhabditis elegans, were the stars of a startling 1993 discovery by UCSF biologist Cynthia Kenyon, PhD. She found then that a change in just one gene, called daf-2, doubled the worms' lifespan. This finding led to the understanding that lifespan is regulated by genes and is therefore changeable, rather than the inevitable result of the body's breakdown. The discovery in worms has been confirmed in other animals including mice.

The new research by Kenyon and graduate student Julie Pinkston is reported in the advanced online edition of the journal.

Kenyon is the American Cancer Society Professor and director of the Hillblom Center for the Biology of Aging at UCSF.

"This is very exciting," Kenyon said. "There is a widely held view that any mechanism that slows aging would probably stimulate tumor growth. But we found many genes that increase lifespan, but slow tumor growth. Humans have versions of many of these genes, so this work may lead to treatments that keep us youthful and cancer-free much longer than normal."

Since her early finding that the gene daf-2 and another gene known as daf-16 regulate lifespan, Kenyon's research team has hoped to identify the genes that they in turn affect -- those that more directly affect aging and tumor growth.

"Now we are really getting there," Kenyon said.

The gene daf-2 codes for a receptor for insulin and also for an insulin-like protein that promotes growth. It influences daf-16, which makes a so-called transcription factor -- a protein that determines when and where hundreds of other genes are turned on. The focus of the new study was to identify specific genes regulated by daf-16 which affect cancer and/or lifespan.

The scientists used an established tumor model in the worms. Then, starting with a list of 734 genes known to be targets of daf-16, they identified 29 genes that either promote or suppress tumor cell growth. They did this using several techniques, including RNA interference or RNAi, a powerful tool that allows scientists to control the expression of just one kind of gene at a time.

About half of the genes stimulated tumor growth and half suppressed it, they found. Strikingly, about half of these genes also affect lifespan in animals that do not have tumors, further strengthening the model Kenyon and others have conceived in which the insulin receptor, daf-2, works in concert with the transcription factor daf-16 to link longevity and tumor resistance. The "downstream" genes appear to act in a cumulative way, they found.

The genes that stimulated tumor growth also accelerated aging itself, and the genes that prevented tumor growth slowed down the aging process and extended lifespan. These findings greatly strengthen the view that the controls of lifespan and cancer have deep, common roots, Kenyon and Pinkston conclude.

PRESS RELEASE: Einstein Researchers Use Novel Approach to Uncover Genetic Components of Aging

Maureen Martino — Tue, 28 Aug 2007 09:28:21 -0400

Einstein Researchers Use Novel Approach to Uncover Genetic Components of Aging

August 24, 2007 –– People who live to 100 or more are known to have just as many—and sometimes even more—harmful gene variants compared with younger people. Now, scientists at the Albert Einstein College of Medicine of Yeshiva University have discovered the secret behind this paradox: favorable “longevity” genes that protect very old people from the bad genes’ harmful effects. The novel method used by the researchers could lead to new drugs to protect against age-related diseases.

“We hypothesized that people living to 100 and beyond must be buffered by genes that interact with disease-causing genes to negate their effects,” says Dr. Aviv Bergman, a professor in the departments of pathology and neuroscience at Einstein and senior author of the study, which appears in the August 31 issue of PLoS Computational Biology.

To test this hypothesis, Dr. Bergman and his colleagues examined individuals enrolled in Einstein’s Longevity Genes Project, initiated in 1998 to investigate longevity genes in a selected population: Ashkenazi (Eastern European) Jews. They are descended from a founder group of just 30,000 or so people. So they are relatively genetically homogenous, which simplifies the challenge of associating traits (in this case, age-related diseases and longevity) with the genes that determine them.

Participating in the study were 305 Ashkenazi Jews more than 95 years old and a control group of 408 unrelated Ashkenazi Jews. (Centenarians are so rare in human populations—only one in 10,000 people live to be 100—that “longevity” genes probably wouldn’t turn up in a typical control group. Longevity runs in families, so 430 children of centenarians were added to the control group to increase the number of favorable genes.)

All participants were grouped into cohorts representing each decade of lifespan from the 50’s on up. Using DNA samples, the researchers determined the prevalence in each cohort of 66 genetic markers present in 36 genes associated with aging.

As expected, some disease-related gene variants were as prevalent or even more prevalent in the oldest cohorts of Ashkenazi Jews than in the younger ones. And as Dr. Bergman had predicted, genes associated with longevity also became more common in each succeeding cohort. “These results indicate that the frequency of deleterious genotypes may increase among people who live to extremely old ages because their protective genes allow these disease-related genes to accumulate,” says Dr. Bergman.
The Einstein researchers were able to construct a network of gene interactions that contributes to the understanding of longevity. In particular, they found that the favorable variant of the gene CETP acts to buffer the harmful effects of the disease-causing gene Lp(a).

If future research finds that a single longevity gene buffers against several disease-causing genes, then drugs that mimic the action of the longevity gene could help protect against cardiovascular disease and other age-related diseases.

“This study shows that our approach, which was inspired by a theoretical model, can reveal underlying mechanisms that explain seemingly paradoxical observations in a complex trait such as aging,” says Dr. Bergman. “So we’re hopeful that this method could also help uncover the mechanisms—the gene interactions—responsible for other complex biological traits such as cancer and diabetes.”

Meanwhile, the Einstein researchers are greatly expanding their longevity research: From the 66 genetic markers examined in this study, they are now using a high-throughput technology that allows them to assay one million genetic markers throughout the human genome. The goal is to find additional genetic networks that are involved in the process of aging.

Other Einstein researchers involved in the study were Gil Atzmon, Kenny Ye, Thomas McCarthy and Nir Barzilai.