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Archive - Mar 9, 2015

Mayo/TSRI Study IDs New Class of Healthspan-Extending Drugs Called “Senolytics”

A research team from The Scripps Research Institute (TSRI), Mayo Clinic, and other institutions has identified a new class of drugs that, in animal models, dramatically slows the aging process—alleviating symptoms of frailty, improving cardiac function and extending a healthy lifespan. The new research was published online on March 9, 2015 in Aging Cell. The scientists coined the term “senolytics” for the new class of drugs. “We view this study as a big, first step toward developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders,” said TSRI Professor Paul Robbins, Ph.D., who, with Associate Professor Laura Niedernhofer, M.D., Ph.D., led the research efforts for the paper at TSRI Florida. “When senolytic agents, like the combination we identified, are used clinically, the results could be transformative.” “The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with aging,” said Mayo Clinic Professor James Kirkland, M.D., Ph.D., senior author of the new study. “It may eventually become feasible to delay, prevent, alleviate, or even reverse multiple chronic diseases and disabilities as a group, instead of just one at a time.” Senescent cells—cells that have stopped dividing—accumulate with age and accelerate the aging process. Because the “healthspan” (time free of disease) in mice is enhanced by killing off these cells, the scientists reasoned that finding treatments that accomplish this in humans could have tremendous potential. The scientists were faced with the question, though, of how to identify and target senescent cells without damaging other cells.

Unprecedented Insight into Structure of Dynein-Dynactin Molecular Motor Complex

A team led by scientists at The Scripps Research Institute (TSRI) in La Jolla, California has determined the basic structural organization of a molecular motor that hauls cargoes and performs other critical functions within cells. Biologists have long wanted to know how this molecular motor—called the “dynein-dynactin complex”—works. But the complex’s large size, myriad subunits, and high flexibility have, until now, restricted structural studies to small pieces of the whole. In the new research, however, TSRI biologist Dr. Gabriel C. Lander and his laboratory, in collaboration with Dr. Trina A. Schroer and her group at Johns Hopkins University, created a picture of the whole dynein-dynactin structure. “This work gives us critical insights into the regulation of the dynein motor and establishes a structural framework for understanding why defects in this system have been linked to diseases such as Huntington’s, Parkinson’s, and Alzheimer’s,” said Dr. Lander. The findings are reported in a Nature Structural & Molecular Biology advance online publication on March 9, 2015. The article is titled “Structural Organization of the Dynein–Dynactin Complex Bound to Microtubules.” The proteins dynein and dynactin normally work together on microtubules for cellular activities such as cell division and intracellular transport of critical cargo such as mitochondria and mRNA. The complex also plays a key role in neuronal development and repair, and problems with the dynein-dynactin motor system have been found in brain diseases including Alzheimer’s, Parkinson’s and Huntington’s diseases, and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.

Queen Bee’s Microbiome Distinct from Rest of Colony

An Indiana University (IU) researcher and collaborators have published the first comprehensive analysis of the gut bacteria found in queen bees. Despite the important role of gut microbial communities -- also known the "microbiome" -- in protecting against disease, as well as the central role of the queen bees in the proper function and health of the hive, similar analyses of honey bees have previously only been performed on worker bees. Apis mellifera -- or the western honey bee -- contributes significantly to agriculture, including pollinating one out of every three mouthfuls of food globally. Understanding the role of microbes in the productivity of queen bees and the health of bee colonies may provide critical insights into the decline of bees in recent years, with colony losses as high as 40 percent over winter. The research, titled "Characterization of the Honey Bee Microbiome Throughout the Queen-Rearing Process," was published online on February 27, 2015, and will appear in print in the journal Applied and Environmental Microbiology. Also contributing to the study were researchers at Wellesley College and North Carolina State University. "This might be a case in which 'mother does not know best,'" said Dr. Irene L.G. Newton, Assistant Professor of Biology in the College of Arts and Sciences' Department of Biology at IU Bloomington, who is corresponding author on the study. "In many animals, transmission of the microbiome is maternal. In the case of the honey bee, we found that the microbiome in queen bees did not reflect those of worker bees -- not even the progeny of the queen or her attendants. In fact, queen bees lack many of the bacterial groups that are considered to be core to worker microbiomes."

New Evidence Suggests Protein Kinase C (PKC) Proteins Suppress Rather Than Promote Cancer

Researchers from Manchester, UK, working with scientists in California, have found that certain molecules long thought to promote cancer growth, actually suppress tumors, suggesting that therapeutic approaches should aim to restore, rather than block, their activity. The protein kinase C (PKC) family of molecules are enzymes that facilitate a range of cellular processes, including cell survival, proliferation, migration, and death. In the 1980s, it was found that PKCs were activated by cancer-causing phorbol esters, and that led to the conclusion that PKCs themselves induced the development of tumors. However, attempts to develop new treatments that prevent tumor cell growth by blocking the activity of PKCs have had little success. A recent study involving Manchester scientists, the findings of which have been published in the January 29, 2015 issue of Cell, has explored the effect of mutations in PKC on tumor growth. The article is titled “Cancer-Associated Protein Kinase C Mutations Reveal Kinase’s Role as Tumor Suppressor.” Dr. John Brognard, from the Cancer Research UK Manchester Institute at The University of Manchester – part of the Manchester Cancer Research Centre – said: “Despite phorbol esters being known to cause cancers, we’ve seen frustratingly little progress when targeting PKCs to stop tumor growth.” The Manchester group collaborated with a team from the University of California, San Diego, to analyze PKC mutations in human cancer cells. They found that most were ‘loss of function’ mutations, meaning that the genetic changes stopped PKC from working. When they corrected these mutations in bowel cancer cells, they saw a reduction in tumor growth, meaning that contrary to the previous understanding, PKC normally acts to block cancer.

Highlights from Tri-Con 2015 Conference; Zon Zones In

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, dated March 2, 2015, and published by TriLink BioTechnologies of San Diego, provides a summary of highlights from the 22nd Annual Molecular Medicine Tri-Conference—better known as Tri-Con—which took place February 15-20 in San Francisco, and which Dr. Zon attended along with approximately 3,000 other scientists, physicians, and entrepreneurs from over 40 countries. With difficulty, given the many impressive presentations, Dr. Zon was able to select three particularly impressive highlights from the content-packed conference. His pick for the top presentation, which was actually also a poster and exhibit all-in-one, featured what he called “the amazing achievement” of a group of New Zealanders from the University of Otago. The team, led by Dr. Jo-Ann Stanton, recently introduced a first-of-a-kind hand-held device for performing real-time or quantitative PCR (qPCR) in the field. This remarkable, palm-size instrument manages to squeeze a plastic four-well sample (10microL-40microL) strip into a thermal cycling block along with an optical system and still only measure a mere 4 x 8 inches. Not only is its size impressive, but the instrument will reportedly perform conventional 40-cycle qPCR with SYBR green or FAM in about 50 minutes. To top it off, results are said to be comparable to “gold standard” laboratory systems. The device is being commercialized as the Freedom4 device by a New Zealand-based start-up company named Ubiquitome, which values this device at $25,000 according to a Feb 25, 2015 press release.
The Tri-Con’15 app allowed attendees to vote for the top poster and the winner—who certainly got my vote—was S. Pranav of Monta Vista High School, whose poster was entitled “Integrative Network Analysis of Epigenetic and Genomic Data for Colorectal Cancer.”