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2019 New Year’s Message – A Call for Medical Progress and Preservation of the Good – Article by Victor Bjoerk

2019 New Year’s Message – A Call for Medical Progress and Preservation of the Good – Article by Victor Bjoerk

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Victor Bjoerk


I celebrated the end of 2018 like normally with neuroscientist Anders Sandberg and several other “transhumanists” or “technoprogressive people” in Stockholm!

Why am I in that place to start with? Well, I’m quite frustrated with the human condition in the first place; I’ve always questioned everything from social norms and different kinds of problems in the world, and there’s still so much misery around that we need to unite and fix. (I know it sounds cliché, but it’s true!)

As people reading this know, the vast majority of human misery worldwide today occurs due to our bodies damaging themselves with the passage of time, the biological process we call aging. This occurs because evolution has no goals and our ancestors died at the age of 30-40 prehistorically, and therefore there was no pressure for evolution to create humans that could repair themselves molecularly to live thousands of years. The closest we get among Eukaryotes/Vertebrates are Greenland sharks, which can live to 500+ years; that is easy to understand since they have no predators and just have to open their mouths to get their daily food. On the opposite side we have as a prominent example the mouse, with a very poor molecular repair system and subsequent 2.5-year lifespan, easy to understand when you realize how dangerous life is in the wild if having a mouse body.

Thanks to our technology, we have created the “paradise Greenland shark scenario” for humans during the past century essentially, creating very comfortable existences where nearly everyone survives.

So if you’re 25 years old, life is really great nowadays in Western countries (unless you like to complain about everything!); the existential risks are so low in the absence of aging that you would live many thousands of years just by being a young person living in Sweden.

So I’ve worked a lot in nursing homes both before and during my studies in molecular biology, and what those people have to endure would be strictly illegal in most countries if we knew how to change it. Imagine if, for example, Saudi Arabia allowed its citizens to age while the Western world had abolished it; wouldn’t Amnesty International intervene?

But what can be done with the human body? Well, I assume quite a lot! We are seeing so many people who can’t stand the medical monopoly and the 17-year bench-to-bedside status quo, which isn’t an abstract academic complaint but which impact their daily lives, so they start self-experimenting with, for example, senolytic medicines to kill their senescent cells, making themselves “younger” in certain aspects, which is pretty cool!

However I’m not someone who constantly calls for change and “progress”; I mean, if something is nice, then why not keep it? As far as I’m concerned, for example, the beautiful architecture from the past can continue to stand for thousands more years. These buildings fulfill their purpose and look nice; I’m quite conservative on those points – but please accelerate the medical research, and it is crucial to spot the techniques that actually do work and to not waste resources on hype!

2018 has brought me many good things, those which one can call “achievements” and those which are not visible. The Eurosymposium on Healthy Aging in Brussels became a success! (And there will be some events during 2019 that I am also announcing for everyone who enjoyed it!)

I’ve been learning a lot about CRISPR and many other techniques both practically and theoretically, though I have not exactly used them to change the world. Medical progress takes forever to achieve, and it’s not exactly helped by a massive web of bureaucracy/hierarchies/prestige/laws, all contributing to slowing down progress for people in need. What can really be done? One needs to focus on the positive and go where the biotech companies can succeed!

So if things are working out for me as I hope now in 2019, I hope being able to really work full time to impact the longevity industry, I really feel like an overripe fruit that needs to get things done, because implementing stuff is what matters and not becoming some passive “longevity encyclopedia”. I’ll keep everyone as usually updated!

So happy new 2019 everyone! And make sure to take good care of yourselves!

Victor Bjoerk has worked for the Gerontology Research Group, the Longevity Reporter, and the Fraunhofer-Institut für Zelltherapie und Immunologie. He has promoted awareness throughout Europe of emerging biomedical research and the efforts to reverse biological aging. 

BGRF and SILS Scientists Analyze Viability of shRNA Therapy for Huntington’s Disease – Press Release by Biogerontology Research Foundation

BGRF and SILS Scientists Analyze Viability of shRNA Therapy for Huntington’s Disease – Press Release by Biogerontology Research Foundation

Biogerontology Research Foundation


Friday, December 1, 2017, London, UK: Researchers from the Biogerontology Research FoundationDepartment of Molecular Neuroscience at the Swammerdam Institute for Life Sciences at the University of Amsterdam, and the Department of Neurobiology, Care Sciences and Society at the Karolinska Institute announce the publication of a paper in Translational Neurodegeneration, a BioMedCentral journal, titled RNAi mechanisms in Huntington’s disease therapy: siRNA versus shRNA.

After many years of development, RNAi therapeutics are nearing the clinic. There are several variants on RNAi therapeutics, such as antisense oligonucleotides (ASOs), short-hairpin RNA (shRNA), small interfering RNA (siRNA), et cetera. The researchers’ paper aimed to answer the question of why RNAi therapeutics for nucleotide repeat disorders (specifically Huntington’s, a devastating genetic neurodegenerative disease), have lost favor in recent years. After a phenomenal amount of excitement, these therapies were hindered by problems like molecular stability, dosing, and transcriptional control of the gene therapeutic construct.

“We compared various RNAi-based therapeutic modalities available for the treatment of Huntington’s Disease and offered mechanistic proposals on how to break through current barriers to clinical development. One key problem has proven to be modulating the expression level of shRNA constructs, which would otherwise be the clear frontrunner among ASOs, siRNAs, and other methods due to duration of expression, dramatically reduced off-target effects, and ease of delivery by adeno-associated viruses that are already approved by the EMA and FDA. We also put forward novel methods of modulating construct expression and avoiding off-target effects” said Franco Cortese, co-author of the paper and Deputy Director of the Biogerontology Research Foundation.

The researchers analyzed available data on the levels of off-target effects associated with siRNA vs shRNA, surveyed emerging strategies to reduce off-target effects in shRNA therapies (such as tough decoy RNAs, or TuDs), and proposed novel methods of controlling shRNA expression, in particular through the use of negative feedback-driven oscillating promoters.

Mechanism of TFEB at the PGC1-a promoter. The PGC1a promoter contains a CLEAR-box that is known to be bound by TFEB, a transcription factor induced during autophagy and lysosomal biogenesis. A construct being the PGC1a promoter CLEAR-box would be induced by TFEB under conditions of intracellular proteotoxicity due to HTT aggregation. By this mechanism, on-demand suppression of HTT could be achieved | Credit: Translational Neuroscience

 

“We proposed two novel feedback mechanisms that 1) activate construct expression stoichiometrically with mutant Huntingtin expression, or 2) only during aggregate-induced autophagy and lysosomal biogenesis. That way, the problem of excessive construct expression may be mitigated. These ideas were inspired by feedback systems used in synthetic biology, and in ‘nonsynthetic,’ naturally occurring biological systems” said Sebastian Aguiar, lead author of the paper.

Readers can read the open-access paper here: https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-017-0101-9.

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About the Biogerontology Research Foundation

The Biogerontology Research Foundation is a UK non-profit research foundation and public policy center seeking to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF funds and conducts research which, building on the body of knowledge about how ageing happens, aims to develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of ageing, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

About the Swammerdam Institute for Life Sciences

The Swammerdam Institute for Life Sciences (SILS) is the largest institute of the Faculty of Science at the University of Amsterdam. The institute comprises biological disciplines including molecular and cell biology, microbiology, plant science, physiology and neurobiology, supported by modern enabling technologies for the life sciences. The research groups of SILS also develop methods in genomics (micro-array, next-gen sequencing, proteomics), bioinformatics and advanced light microscopy technologies. Knowledge from adjacent fields of science, in particular biochemistry, biophysics, medicine, bioinformatics, statistics and information technology make SILS a multidisciplinary research institute with a systems biology approach to the life sciences. SILS’ research objective is to understand the functioning of living organisms, from the most basic aspects up to complex physiological function(s). Biological processes are studied at the level of molecules, cells, cellular networks and organisms. SILS research topics have in common that similar cellular processes and interactions are studied, likewise using similar methodologies and technologies. Therefore SILS scientists often study the same concepts in different biological systems. Within the institute, this leads to exchange of information and extension of research over the borders of different disciplines. Part of SILS research activities are directed to application-oriented research in close collaboration with industry.