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

6 Comments

Filed under Article, Mechanisms of aging

6 responses to “The Most Important Scientific Discovery of the Year

  1. How much do we know about the transferability of such strategies to humans? Nematodes and arthropods are rather different from vertebrates. It’s encouraging, but is there any reason to think that, say, adding Thioflavin T to a human’s diet would extend life span?

    • Of course, studies are needed in order to investigate the possible effect of Thioflavin T on humans. But yes, I would say there is a reason to think that adding Thioflavin T to human diet may extend life span. The article proves that this compound activates stress resistance in nematodes. Stress resistance genes are quite conservative, meaning the majority of species have these genes, so if this chemical activates these effects in worms, there’s a good chance it’s going to do the same in mammals, humans in particular. But again, experiments are needed and for now it’s just speculation. Although, the article is a proof of principle that we can alter stress resistance mechanisms by simply adding a compound to the diet without any genetic mutations.

  2. Pingback: stem cells xenobiotics | StemEnhance™ and StemFlo™ | Stem Cell Enhancer

  3. Were trying to figure out what is causing this or that disease but in reality it’s all the same formula. Enough stress from either external or internal factors eventually creates a disease.

    • We are constantly experiencing stress. However, when we are young, our body is capable of keeping itself not harmed by that stress. Our stress resistance works good. But when time passes by the maintenance mechanisms begin to fail bit by bit and we end up having all those pathologies and then we die. So, one of the anti-aging strategies would be to activate the stress resistance mechanisms at older ages and make them work better than they do.

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