Monthly Archives: June 2017

Slowing down the aging process might be possible one day with supplements derived from gut bacteria. Scientists at Baylor College of Medicine and the University of Texas Health Science Center at Houston have identified bacterial genes and compounds that extend the life of and also slow down the progression of tumors and the accumulation of amyloid-beta, a compound associated with Alzheimers disease, in the laboratory worm C. elegans. The study appears in the journal Cell.

The scientific community is increasingly aware that our bodys interactions with the millions of microbes in our bodies, the microbiome, can influence many of our functions, such as cognitive and metabolic activities and aging, said corresponding author Dr. Meng Wang, associate professor of molecular and human genetics at Baylor and the Huffington Center On Aging. In this work we investigated whether the genetic composition of the microbiome might also be important for longevity.

This question is difficult to explore in mammals due to technical challenges, so the researchers turned to the laboratory worm C. elegans, a transparent, simple organism that is as long as a pinhead and shares essential characteristics with human biology. During its 2 to 3 week long lifespan, the worm feeds on bacteria, develops into an adult, reproduces, and progressively ages, loses strength and health and dies. Many research laboratories around the world, including the Wang lab, work with C. elegans to learn about basic biological processes.

We think that C. elegans is a wonderful system in which to study the connection between bacterial genes and aging because we can very fine tune the genetics of microbes and test many genes in the worm in a relatively short time, Wang said.

Testing thousands of genes, one at a time.

To study the effect of individual bacterial genes on the lifespan of C. elegans, Wang joined efforts with Dr. Christophe Herman, associate professor of molecular and human genetics and molecular virology and microbiology at Baylor, and other colleagues who are experts in bacterial genetics. They employed a complete gene-deletion library of bacterium E. coli; a collection of E. coli, each lacking one of close to 4,000 genes.

We fed C. elegans each individual mutant bacteria and then looked at the worms life span, Wang said. Of the nearly 4,000 bacterial genes we tested, 29, when deleted, increased the worms lifespan. Twelve of these bacterial mutants also protected the worms from tumor growth and accumulation of amyloid-beta, a characteristic of Alzheimers disease in humans.

Further experiments showed that some of the bacterial mutants increased longevity by acting on some of the worms known processes linked to aging. Other mutants encouraged longevity by over-producing the polysaccharide colanic acid. When the scientists provided purified colanic acid to C. elegans, the worms also lived longer. Colanic acid also showed similar effects in the laboratory fruit fly and in mammalian cells cultured in the lab.

The researchers propose that, based on these results, it might be possible in the future to design preparations of bacteria or their compounds that could help slow down the aging process.

Colanic acid mediates crosstalk between bacteria and mitochondria

Interestingly, the scientists found that colanic acid regulates the fusion-fission dynamics of mitochondria, the structures that provide the energy for the cells functions.

These findings are also interesting and have implications from the biological point of view in the way we understand host-microbe communication, Wang said. Mitochondria seem to have evolved from bacteria that millions of years ago entered primitive cells. Our finding suggests that products from bacteria today can still chime in the communication between mitochondria in our cells. We think that this type of communication is very important and here we have provided the first evidence of this. Fully understanding microbe-mitochondria communication can help us understand at a deeper level the interactions between microbes and their hosts.

Other contributors to this work include Bing Han, Priya Sivaramakrishnan, Chih-Chun J. Lin, Isaiah A.A. Neve, Jingquan He, Li Wei Rachel Tay, Jessica N. Sowa, Antons Sizovs, Guangwei Du and Jin Wang.

Financial support for this project was provided by the National Institutes of Health grants R01AG045183, R01AT009050, DP1DK113644, R01HL119478, R01GM088653, R01GM115622, R01CA207701 and Howard Hughes Medical Institute Faculty Scholar Award.

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Gut bacteria might one day help slow down aging process - Baylor College of Medicine News (press release)

Scientists have discovered a new cellular pathway that can promote and support the growth of cancer cells. In a mouse model of melanoma, blocking this pathway resulted in reduction of tumor growth. The study, which appears in Science, offers a novel opportunity to develop drugs that could potentially inhibit this pathway in human cancer cells and help control their growth.

We had been studying components of this pathway for several years, said senior author Dr. Andrea Ballabio, professor of molecular and human genetics at Baylor College of Medicine and Texas Childrens Hospital in Houston, Texas, and director of the Telethon Institute of Genetics and Medicine in Naples, Italy. We know that the pathway is important for normal cells to carry their activities as it is involved in regulating metabolism, that is, how cells process nutrients to obtain energy and how cells use energy to grow. In this study we wanted to learn more about how the pathway regulates its activity.

Pathways involved in cellular metabolism typically regulate themselves, meaning that some components of the pathway control each others activities. We suspected that the pathway was autoregulated, and we confirmed it in this study. Our experimental approaches showed that there is a feedback loop within the path that allows it to control itself.

An important pathway for normal cellular activities

Ballabio and his colleagues studied the role of the pathway in two normal cellular activities; how cells respond to physical exercise and how they respond to nutrient availability. In terms of physical exercise, the researchers determined that the self-regulating mechanism they discovered is essential for the body builder effect.

Some athletes take the aminoacid leucine or a mixture of aminoacids immediately after exercising, which promotes protein synthesis that leads to muscle growth. This is the body builder effect, Ballabio said. When we genetically engineered mice to lack the pathway, we lost the body builder effect.

The researchers had a group of normal mice and another of mice lacking the pathway. Both groups were set to exercise and fed leucine immediately after. While normal mice showed enhanced protein synthesis, the mice without the pathway did not.

In healthy organisms, this pathway also allows cells to adapt more efficiently to nutrient availability, Ballabio said. For example, when transitioning from a period of starvation to one in which food is available, cells need to switch from catabolism to anabolism. Starvation promotes catabolism the breakdown of nutrients to obtain energy to function and eating promotes anabolism the buildup of molecules, such as proteins. The feedback we discovered mediates the switch from catabolism to anabolism, allowing organisms to adapt to food availability.

An important pathway for cancer growth

The scientists also studied the role this pathway might play in cancer cells. They discovered that overactivation of this pathway, which is observed in some types of cancer such as renal cell carcinoma, melanoma and pancreatic cancer, is important to promote and support the growth of cancer cells in culture and animal models.

Most importantly, we demonstrated in our study that blocking the pathway resulted in reduction of tumor growth in an experimental model of human melanoma transplanted into mice, Ballabio said. I am most excited about the future potential therapeutic applications of this discovery against cancer. Developing pharmacological treatments that interfere with this pathway might one day help stop tumor growth.

Rare disease discoveries can improve our understanding of common diseases

Our lab focuses on rare genetic diseases, such as lysosomal storage genetic disorders, in which we originally studied this pathway, Ballabio said. Then, we discovered that the pathway is also important in cancer. Our and other researchers work on rare genetic diseases sometimes produces findings that can potentially be applicable to more common diseases, such as cancer.

For a complete list of the authors of this work and their affiliations, please refer to the published article.

This study was supported by grants from the Italian Telethon Foundation (TGM11CB6); European Research Council Advanced Investigator grant no. 250154 (CLEAR) and no. 341131 (InMec); U.S. National Institutes of Health (R01-NS078072); and the Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.) IG 2015 Id 17639 and IG 2015 Id 17717.

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Newly revealed cellular pathway may lead to cancer therapies - Baylor College of Medicine News (press release)

A bacteria in the gut may could hold the key to slowing down the aging process.

Scientists from Baylor College of Medicine and the University of Texas Health Science Center at Houston have found bacterial genes and compounds that extend the life of and slow down the progression of tumors and the accumulation of amyloid-beta, which is associated with Alzheimers disease.

The scientific community is increasingly aware that our body's interactions with the millions of microbes in our bodies, the microbiome, can influence many of our functions, such as cognitive and metabolic activities and aging, corresponding author Meng Wang, Ph.D., associate professor of molecular and human genetics at Baylor and the Huffington Center On Aging, said in a statement.

In this work we investigated whether the genetic composition of the microbiome might also be important for longevity, she added.

The researchers have identified the genes and compounds in C. elegans, a laboratory worm that is a transparent, simple organism that share essential characteristics with human biology.

The worm only lives two-to-three weeks and feeds on bacteria. However, it does progressively age to develop into an adult, while also reproducing.

We think that C. elegans is a wonderful system in which to study the connection between bacterial genes and aging because we can very fine tune the genetics of microbes and test many genes in the worm in a relatively short time, Wang said. We fed C. elegans each individual mutant bacteria and then looked at the worms' life span.

Of the nearly 4,000 bacterial genes we tested, 29, when deleted, increased the worms' lifespan. Twelve of these bacterial mutants also protected the worms from tumor growth and accumulation of amyloid-beta, a characteristic of Alzheimer's disease in humans.

The researchers then discovered that some of the bacterial mutants increased longevity by acting on some of the worms known processes linked to aging. After providing purified colonic acid to the worms, the researchers found that they lived longer.

Based on these results the researchers believe it is possible to design preparations of bacteria or their compounds that could help slow down the aging process.

See the original post here:
Gut Bacteria Could Impact Aging - R & D Magazine