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Archive - Dec 2018

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December 10th

Lifespan Extension at Low Temperatures Is Actively Controlled by Genes, Not by Passive Lowering of Metabolic Rate Reducing Reactive Oxygen Species (ROS), New Study Suggests

Why do we age? Despite more than a century of research (and a vast industry of youth-promising products), what causes our cells and organs to deteriorate with age is still largely unknown. One known factor is temperature: Many animal species live longer at lower temperature than they do at higher temperatures. As a result, "there are people out there who believe, strongly, that if you take a cold shower every day it will extend your lifespan," says Kristin Gribble (photo), PhD, an Assistant Scientist at the Marine Biological Laboratory(MBL) in Woods Hole, Massachusetts (the MBL is an affiliate of the University of Chicago). But a new study from Dr. Gribble's lab indicates that it's not just a matter of turning down the thermostat. Rather, the extent to which temperature affects lifespan depends on an individual's genes. The study from Dr. Gribble's group, which was published in Experimental Gerontology (114: 99-106; 2018), was conducted in the rotifer, a tiny animal that has been used in aging research for more than 100 years. Gribble's team exposed 11 genetically distinct strains of rotifers (Brachionus) to low temperature, with the hypothesis that if the mechanism of lifespan extension is purely a thermodynamic response, all strains should have a similar lifespan increase. However, the median lifespan increase ranged from 6 percent to 100 percent across the strains, they found. They also observed differences in mortality rate. The new study is titled “Congeneric Variability in Lifespan Extension and Onset of Senescence Suggest Active Regulation of Aging in Response to Low Temperature.” This study clarifies the role of temperature in the free-radical theory of aging, which has dominated the field since the 1950s.

December 9th

A-T Children’s Project Announces Selection of First Child to Receive ASO Gene Therapy for Ataxia-Telangiectasia

On November 30, 2018, the Ataxia-Telangiectasia (A-T) Children’s Project and its President Brad Margus announced that the Project has selected a little, 18-month girl on the west coast of the U.S. to be the first A-T child in history to receive gene therapy. The Project had the pleasure of letting th girl's parents know the exciting news last week. How was the first child selected? The laboratory of Dr. Tim Yu at Boston Children’s Hospital/Harvard collected and grew skin, blood, and stem cells from three different young children who we believed had the right type of mutations in their A-T genes to be treated with an antisense oligonucleotide (ASO) gene therapy approach. The scientists then made many different oligonucleotides designed to silence each of the children’s mutations and tested them in each child’s cells. In the end, the group identified several oligonucleotide molecules that worked really well in this little girl’s cells, not only silencing her mutation and causing the A-T protein to be made correctly, but also causing downstream biological pathways to be activated as though her cells were from a healthy child (confirming this downstream function took us longer than planned to do, but now gives us more confidence to move forward). This means that we now have both our drug and our patient selected. Very soon, we’ll be signing a contract to begin the manufacture of enough quantity of the drug to run our “n of 1” clinical trial (we’ll keep the other oligonucleotides that worked as backups). We’ll also make sure that the drug produced will be clinical-grade to satisfy the FDA. As soon as we receive the first batch of this final version of the drug, we’ll test it for safety in rats before applying to the FDA for approval to start testing it in a human.