Deciphering Secrets of Longevity, from Worms

Microscopic view of a glowing green worm

Caption: Long-lived worms show increased activation of DAF-16 (green), a protein linked with longevity in worms and humans.
Credit: Kapahi Lab, Buck Institute for Research on Aging, Novato, CA

How long would you want to live, if you could remain healthy? New clues from experiments done in microscopic worms suggest that science may have the potential to extend life spans dramatically.

Taking advantage of the power of the worm Caenorhabditis elegans (C. elegans) as a model system for genetic studies, NIH-funded researchers at the Buck Institute for Research on Aging in Novato, CA, decided to set about testing ways to extend the worms’ lifespan.

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Fighting Obesity: New Hopes From Brown Fat

Artist rendition of a xray showing brown fat as glowing green

Caption: Brown fat—actually marked in green on this image—is wrapped around the neck and shoulders. This “shawl” of brown fat warms blood before it travels to the brain.
Illustration: John MacNeill, based on patient imaging software designed by Ilan Tal. Copyright 2011 Joslin Diabetes Center

If you want to lose weight, then you actually want more fat, not less. But you need the right kind: brown fat. This special type of fatty tissue burns calories, puts out heat like a furnace, and helps to keep you trim. White fat, on the other hand, stores extra calories and makes you, well, fat. Wouldn’t it be nice if we could instruct our bodies to make more brown fat, and less white fat? Well, NIH-funded researchers have just taken another step in that direction [1].

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New Understanding of a Common Kidney Cancer

Purple stained kidney tissue

Caption: Histologic image of clear cell kidney cancer
Slide courtesy of W. Marston Linehan, National Cancer Institute, NIH

Understanding how cancer cells shift into high gear—what makes them become more aggressive and unresponsive to treatment—is a key concern of cancer researchers. A new study reveals how this escalation occurs in the most common form of kidney cancer: clear cell renal cell carcinoma (ccRCC). The study shows that ccRCC tumors acquire specific mutations that encourage uncontrollable growth and shifts in energy use and production [1].

Conducted by researchers in the NIH-led The Cancer Genome Atlas (TCGA) Research Network, the study compared more than 400 ccRCC tumors from individual patients with healthy tissue samples from the same patients. Researchers were looking for differences in the gene activity and proteins in healthy vs. tumor tissue. Continue reading

Fishing for Answers in Human Disease

Images of both a wild type zebrafish and a vhnf1 mutant zebrafish. The mutant fish shows abnormal bulging in its upper body.

Caption: Researcher Zhaoxia Sun, at Yale, uses the zebrafish to study Polycystic Kidney Disease, which affects more than 600,000 Americans. Mutations in the zebrafish vhnf1 gene, and its human counterpart, cause cysts in both zebrafish and human kidneys (as shown by the large “bubble” seen in the mutant fish). [3]
Credit: Zhoaxia Sun, Biological & Biomedical Sciences, Yale University

Wouldn’t it be instructive if we could see the effect of a genetic mutation in real time, as the gene was misbehaving? Well, that’s one of the perks of using the zebrafish—a tiny, striped, transparent fish.

Just last month, an international team of scientists—funded in part by NIH—published the entire genetic code of the zebrafish [1]. This is a vital resource for understanding human health and disease. How does the genetic blueprint of a fish help us or accelerate drug discovery? Well, it turns out that more than 75% of the genes that have been implicated in human diseases have counterparts in the zebrafish. So, if we discover a mutation in a human, we can make the corresponding mutation in the zebrafish gene—and often get a pretty good idea of how the gene works, how the mutation causes havoc, and how it causes disease in humans. We can even use the zebrafish to test potential drug candidates, to see whether they can alter or fix the symptoms before moving on to mice or humans.

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