Category Archives: Article

A Way to Rejuvenate Old Stem Cells

Wnt5a

 

This chart says that old stem cells, that give birth to blood cells, have much much more Wnt5a protein than the young stem cells. The canonical Wnt signaling cascade changes to the non-canonical one that produces more Wnt5a product. This observation was done by a group of scientists at the universities of Ulm and Muenchen, Germany and was published in Nature. So, why is this such a special observation?

Well, because it gives us a clue to what can be done to rejuvenate our blood producing stem cells. We can “turn off” the Wnt5a gene and make the old stem cells young again, which was successfully done by the authors of the experiment. The researchers took the short hairpin RNA and inserted it into the stem cells using a lentivirus. This hairpin RNA blocks translation of the Wnt5a protein sort of like a blank plug. So, these cells were transplanted into mice and those mice showed improved B lymphopoiesis and peripheral blood differentiation profile overall more similar to the one characteristic of young mice. This can one day become a therapy for humans. We could periodically receive such transplantations of our own hematopoietic stem cells, rejuvenated using gene therapy and we could have young blood production again.

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Filed under Article, Genetics

Age-related regeneration decline conundrum

Over a 16-year period, Panagiotis Tsonis at the University of Dayton, Ohio, and colleagues removed the lenses of six Japanese newts (Cynops pyrrhogaster) 18 times. After each excision, the lenses regenerated. They did so not from remaining lens tissue, but from pigment epithelial cells in the upper part of the iris. There was no documented decline in regenerative capacity neihter due to aging, nor to repetition.

The paper published in Nature Communications reports: “In addition, despite beliefs that aged animals regenerate less efficiently than young ones (also discussed by Darwin), our experiments show that this is not the case in the newt. As regenerative medicine has entered a new era, the knowledge that aged tissues possess robust regenerative capabilities should provide the impetus to identify mechanisms underlying this capacity in the newt and compare them with strategies being employed to promote mammalian regeneration, such as the creation of iPS cells.”

Unfortunately, the authors don’t discuss possible mechanisms underlying such an extraordinary capacity. This absolutely has to be studied, because these mechanisms, when identified, may shed light at how we can manipulate mammalian and human cells in order to trigger at least somewhat similar effects. I find restoration of own regenerative capacity to be a very potent way of extending our lives, therefore this work in newts and other animals with fantastic regenerative abilities has to be continued and multiplied. Any ideas about how this may be done are welcome.

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Filed under Article, Tissue rejuvenation

David Gems Argues for Radical Life Extension

I’d like to share a truely great article by David Gems, Assistant Director of the Institute of Healthy Ageing, UCL. In this paper Professor Gems proves that aging is a diseases and encourages researchers and agencies like FDA to view it as a disease. If this happens there will be demand on therapies that decellerate aging and there will be much less anti-aging fraud, because we’ll have strict regulations for anti-aging drugs.  In this article David Gems describes the possible ways to tacle the problem of aging and explains why he thinks that the best way to persue the problem is to try to decelerate aging. In my opinion, one shouldn’t neglect the possibility to arrest aging in general, but I totally agree with Professor Gems that we have to intervene in the fundamental mechanisms of aging, and not just separate diseases, because only this approach will yield in therapies capable of significantly extending our life span and reducing disease risks.

The article represents a wonderful example of how the ethical questions related to aging research and life extension should be answered.

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The Most Important Scientific Discovery of the Year

Our body is constantly being stressed. There’s nothing new about it and everybody seems to understand what it means. But I’d like to clarify what stress is from the biological point of view. The term stress stands for the negative effects including oxidation of macromolecules with free radicals, inflammation and infections, lack of nutrients, increase or decrease in temperature, light regime disturbance, impact of ionizing radiation. It all leads to damage on molecular and tissue levels. Our body has got the mechsnisms that protect us from this damage. It’s the mechanisms of stress resistance: DNA repair (the glossary is below), autophagy, proteasome activity, xenobiotic detox systems and anti-oxidant systems, heat shock factors, LON mitochondrial protease, methionine sulfoxide reductase, neuroendocrinological regulation of homeostasis.

A paper of extreme importance for fighting aging came out in the Nature journal on Thursday. A research group from Buck Institute lead by Professor Gordon Lithgow was able to prolong life of nematodes by 78% by adding one compound to the worms’ diet – a dye Thioflavin T. The authors showed that the effect of the dye was due to activation of stress resistance mechanisms, which lead to significant increase in median (60%) and maximum lifespan (43-78%). Thioflavin T is used to mark the amyloid protein aggregates in Alzheimer’s disease. Dr. Lithgow’s group showed that this compound regulates protein homeostasis, which leads to life extension in nematodes and improvement of their health later in life. The effect of Thioflavin T depends on autophagy, proteasomal functions, heat shock factor-1 (HSF-1) and transcription factor SNK-1. Both of these proteins play a role in response to stress in nemamtodes: HSF-1 triggers the production of heat shock proteins and SNK-1 takes part in neutralizing oxidative stress. So, Thioflavin T intensificates cellular stress response by activating signaling pathways dependant on HSF-1 and SNK-1, which lealds to misfolded protein stabilization and increased longevity.

This article proves the possibility to prolong life by activating stress resistance using chemical compounds simply added to the diet. There’s also some research where the positive effect on longevity was achieved by mutations in genes governing stress resistance. For example, the work of Dr. Alexey Moskalev, where they activated the DNA repair gene GADD45 and extended maximum lifespan of drosophilas by 77%. Right now it is necessary to identify the chemicals that would activate GADD45 genes in humans and develop drugs based on these compounds.

I’d like to highlight the need of creation of a new class of drugs – geroprotectors. Their distinctive feature is that not so much they will cure the already manifested diseases, as they will prevent them. And the most important part is that geroprotectors will extend our lives. In order for these drugs to be created it is necessary to fund research on activation of stress resistance genes and clinical trials of chosen chemical activators. Again, I’d like to stress that it is time to start clinical trial of geroprotectors.

Glossary:

DNA repair – restoration of damaged DNA structures

Autophagy – process of digestion of cellular components, including damaged proteins and organelles, in lysosomes

Proteasome – protein complex that degrades proteins in the end of their life cycle

Xenobiotics – foreign chemical compaound for an organism, like antibiotics

Heat shock proteins – class of protection proteins, which expression is increased upon high temperature or other stresses

LON Mitochondrial protease – enzyme that cleaves oxidized proteins in the mitochondrial matrix

Methionine sulfoxide reductase – enzyme that restores the oxidized proteins structure by turning methionine sulfoxide into methinine

Neuroendocrinal regulation of homeostasis – maintaining the equilibrium of the internal environment of the organism via the vegetative nervous and endocrine systems

HSF-1 – heat shock factor-1, triggers synthesis of heat shock proteins as a response to ovarious types of stress

Transcription factors – regulatory proteins that control the transfer of the information from the DNA to the mRNA molecules that recognize their target genes by binding to specific fragments of DNA

SNK-1 – transcription factor in nematodes that participates in protection from the oxidative stress

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Filed under Article, Mechanisms of aging

New DNA Repair Process Discovery May Lead to Human Life Extension

A key component of aging is the accumulation of errors in cells genetic’ genetic code or DNA. Once enough errors accumulate, the cell makes faulty proteins leading to irreparable cell damage and death, or in some cases cancer.

In a new study published in the Journal of Biological Chemistry researchers discovered that DNA acetylation governs DNA replication and repair. This process adds acetyl groups to DNA segments which then determines what path of DNA doubling that segment will take.

Cells are known to use a high fidelity yet high energy consuming path for DNA that encodes for proteins.  A low cost yet lower fidelity pathway is used for non protein encoding segments of DNA. The acetylation process just identified tells the cell which repair process the section of DNA should undergo.

Once the process of DNA acetylation can be exploited and applied at will it is possible to ensure cells have very low DNA error rates and thus live longer.

“Our research is in the very early stages, but there is great potential here, with the capacity to change the human experience,” said Robert Bambara, Ph.D., chair of the Department of Biochemistry and Biophysics at the University of Rochester Medical Center and leader of the research. “Just the very notion is inspiring.”

Though exciting it could take a while before this research leads to human lifespan extension.

“The translational rate is becoming better and better. Today, the course between initial discovery and drug development is intrinsically faster. I could see having some sort of therapeutic that helps us live longer and healthier lives in 25 years,” said Bambara.

Source (Eureka Alert)

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Filed under Article, Life Extension, Stem Cell Research

DARPA wants machine to suck all your blood out, other fun stuff

DARPA‘s budget for next year includes funding for all kinds of wild new medical technologies for military medicine, from electromagnetic tissue regeneration to a machine that can suck your blood out, clean it, and then fill you back up.

DARPA is making a major push to try to reduce battlefield casualties, and they’re pouring a lot of money into new technologies to help soldiers recover from injury. The blood-sucking machine is part of a ‘Dialysis-Like Therapeutics’ program designed to combat sepsis, which is caused by toxins in the blood. Basically, DARPA is looking for a system that can filter up to 5 liters of blood at a time, identifying and removing bacteria and viruses and poisons and other toxic stuff and then returning clean blood back into the body.

Also on the table are new autonomous diagnostic sensors that can detect both known and unknown diseases and come up with fast and effective treatments, and tissue regeneration technology that uses hordes of individually magnetized cells controlled by electromagnetic fields to encourage natural ‘scaffolding’ to promote the rapid healing of wounds.

One other exciting little nugget that somehow falls under the medical category for DARPA is the creation of artificial eyes that see as well as the biological eyes of animals. From the sound of things, the end result of the Neovision2 program will be little electronic eyeballs that can learn and recognize objects as quickly as we can, that can be tossed into dangerous situations and report back what they see. Plus, throwing disembodied eyeballs around just generally sounds like a good idea and a lot of fun!

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Filed under Article, Artificial Intelligence, Immortalism, Life Extension, Tissue rejuvenation

Convincing An Insurance Company To Pay For Sequencing A Child’s DNA

Geneticist Elizabeth Worthey worked on the first-ever treatment of a patient based on DNA sequencing, helping doctors decide to give a bone marrow transplant to a 6-year-old boy who had suffered through more than a hundred operations. Now Worthey, an assistant professor at the Medical College of Wisconsin, is part of a team working to comb through the sequences of five more children.

Every Friday, she and her colleagues at Wisconsin Children’s Hospital meet to go over cases that other doctors have put forward for DNA sequencing. There have been about three dozen requests. An insurance company has even agreed to pay for one of the cases, although the money is not yet in the bank and the hospital will not disclose either the insurer or details about the patient. This is the first time that an insurer is known to have agreed to pay for the sequencing of an entire human genome!

“For some of these kids there is no alternative,” Worthey says, “You either guess, you do nothing, or you do something — in this case, sequence their genome.”

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Filed under Article, Genetics, genomics