Tag: Alex Zhavoronkov

International Team Publishes Roadmap to Enhance Radioresistance for Space Colonization – Press Release by Biogerontology Research Foundation

International Team Publishes Roadmap to Enhance Radioresistance for Space Colonization – Press Release by Biogerontology Research Foundation

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Biogerontology Research Foundation

 

IMAGE: These are ways to reduce health risks from space radiation during deep space travels. Multiple approaches from medical selection of radioresistant individuals to gene therapy may be proposed.

Editor’s Note: Below is a press release by the Biogerontology Research Foundation which features a roadmap to enhance radioresistance for space exploration and colonization, published by an international team of scientists from NASA, Health Canada, Canadian Nuclear Laboratories and many other organizations. This press release was originally published here.

~ Dinorah Delfin, Director of Admissions and Public Relations, U.S. Transhumanist Party, February 22, 2018

An international team of researchers from NASA Ames Research Center, Environmental and Radiation Health Sciences Directorate at Health Canada, Oxford University, Canadian Nuclear Laboratories, Belgian Nuclear Research Centre, Insilico Medicine, the Biogerontology Research Center, Boston University, Johns Hopkins University, University of Lethbridge, Ghent University, Center for Healthy Aging, and many others have published a roadmap toward enhancing human radioresistance for space exploration and colonization in the peer-reviewed journal Oncotarget.

“Our recent manuscript provides a comprehensive review of radioresistance for space radiation. Currently there is minimal research being done for radioresistance against HZE irradiation. The importance of these types of studies will be to reduce the associated health risks for long-term space exploration and allow for the development of potential countermeasures against space radiation. In addition, the synergy between understanding aging with radioresistance will allow for further benefits for humans in long-term space missions and allow for reduced health risk. This review sets the stage for the potential research the scientific community can do to allow for safe long term space exploration” said Afshin Beheshti, an author of the paper and a Bioinformatician at NASA Ames Research Center.

The roadmap outlines future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, the coordination of regenerative and ablative technologies, and methods of slowing metabolic activity while preserving cognitive function. The paper concludes by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.

“This paper explores the foreseeable means by which human radioresistance could be biomedically enhanced for the purposes of space exploration and colonization. It also aims to elucidate the links between aging, longevity and radioresistance, and the ways in which research into enhancing human radioresistance could synergistically enable human healthspan extension, ultimately highlighting how ongoing research into the very well-funded sphere of aerospace research could galvanize progress in biomedical gerontology, a massively under-funded area of research despite the grave economic burden posed by demographic aging” said Franco Cortese, an author of the paper and Deputy Director of the Biogerontology Research Foundation.

The publication of the paper in Oncotarget this week is timely, given the test launch of the Falcon Heavy, SpaceX’s largest rocket to date, just last week. Interest into space exploration and even colonisation has been mounting for a number of years. Less than one year ago Elon Musk, CEO of SpaceX, unveiled a roadmap toward colonizing Mars, outlining the ambitious goal of placing a million people on Mars within the next 40 to 100 years. If interest in space colonization continues apace, research into methods of enhancing radioresistance to protect against the various forms of space radiation that spacefarers would be subjected to needs to be accelerated accordingly.

“In linking ageing and radioresistance and tying together research into enhancing the radioresistance of astronauts with the extension of healthy longevity, we hope to have shown how aerospace research could be used to leapfrog the massive funding deficit surrounding the clinical translation of healthspan-extending interventions, in order to brave the storm of the oncoming Silver Tsunami and prevent the looming economic crisis posed by demographic aging” said Dmitry Kaminskiy, an author of the paper and Managing Trustee of the Biogerontology Research Foundation.

The roadmap highlights the need to converge and accelerate research in radiobiology, biogerontology and AI to enable spacefarers to address both the healthcare challenges that we are already aware of, as well as those that we are not.

“Sooner or later we’ll have to do it – leave Earth and wander into deep space. Such travel, taking one or more years outside the Earth’s magnetosphere, would take a high toll on astronauts’ health due to exposure to cosmic radiation. So it’s better to start thinking now about how we are going to cope with that challenge. Luckily, current knowledge from such fields as radiobiology, aging research and biotechnology in general, with the wealth of recent advances in gene editing and regenerative medicine, allow for the drafting of conceptual roadmaps to enhance human resistance to cosmic radiation. This is exactly what this work is all about. It was fun and a pleasure to partake in this theoretical project with such a diverse international team. We were just throwing ideas on the table, some being quite ambitious and futuristic, and then examining them carefully for feasibility and assessing their potential. The work laid out several interesting directions and concepts that can eventually pay off. Last but not least, I think it is also very important to attract widespread attention and interest to this topic” said Dmitry Klokov, an author of the paper and Section Head of the Radiobiology & Health section at Canadian Nuclear Laboratories.

Furthermore, given the massive amount of funding allocated to research into facilitating and optimizing space exploration and optimization, the researchers hope to have shown how research into enhancing radioresistance for space exploration could galvanize progress in human healthspan extension, an area of research that is still massively underfunded despite its potential to prevent the massive economic burden posed by the future healthcare costs associated with demographic aging.

“This roadmap sets the stage for enhancing human biology beyond our natural limits in ways that will confer not only longevity and disease resistance but will be essential for future space exploration” said João Pedro de Magalhães, an author of the paper and a Trustee of the Biogerontology Research Foundation.

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The paper, entitled “Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization”, can be viewed on Oncotarget here.

Citation: Franco Cortese, Dmitry Klokov, Andreyan Osipov, Jakub Stefaniak, Alexey Moskalev, Jane Schastnaya, Charles Cantor, Alexander Aliper, Polina Mamoshina, Igor Ushakov, Alex Sapetsky, Quentin Vanhaelen, Irina Alchinova, Mikhail Karganov, Olga Kovalchuk, Ruth Wilkins, Andrey Shtemberg, Marjan Moreels, Sarah Baatout, Evgeny Izumchenko, João Pedro de Magalhães, Artem V. Artemov, Sylvain V. Costes, Afshin Beheshti, Xiao Wen Mao, Michael J. Pecaut, Dmitry Kaminskiy, Ivan V. Ozerov, Morten Scheibye-Knudsen and Alex Zhavoronkov. Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization, Epub ahead of print. Published online 2018 February 09. doi: 10.18632/oncotarget.24461

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.

Induced Cell Turnover: A Proposed Modality for In Situ Tissue Regeneration and Repair – Press Release by Biogerontology Research Foundation

Induced Cell Turnover: A Proposed Modality for In Situ Tissue Regeneration and Repair – Press Release by Biogerontology Research Foundation

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Biogerontology Research Foundation

Scientists at the Biogerontology Research Foundation, Feinberg School of Medicine at Northwestern University and Swammerdam Institute of Life Sciences at the University of Amsterdam have published a paper on a proposed method of in situ tissue regeneration called Induced Cell Turnover (ICT) in the journal Human Gene Therapy. The proposed therapeutic modality would aim to coordinate the targeted ablation of endogenous cells with the administration of minimally-differentiated, hPSC-derived cells in a gradual and multi-phasic manner so as to extrinsically mediate the turnover and replacement of whole tissues and organs with stem-cell derived cells.

“One of the major hurdles limiting traditional cell therapies is low levels of engraftment and retention, which is caused in part by cells only being able to engraft at locations of existing cell loss, and by the fact that many of those vacancies have already become occupied by ECM and fibroblasts (i.e. scar tissue) by the time the cells are administered, long after the actual occurrence of cell loss. The crux underlying ICT is to coordinate endogenous cell ablation (i.e. induced apoptosis) with replacement cell administration so as to manually vacate niches for new cells to engraft, coordinating these two events in space and time so as to minimize the ability for sites of cell loss to become occupied by ECM and fibroblasts. This would be done in a gradual and multi-phasic manner so as to avoid acute tissue failure resulting from the transient absence of too many cells at any one time. While the notion of endogenous cell clearance prior to replacement cell administration has become routine for bone marrow transplants, it isn’t really on the horizon of researchers and clinicians working with solid tissues, and this is something we’d like to change,” said Franco Cortese, Deputy Director and Trustee of the Biogerontology Research Foundation, and lead author on the paper.

Cell-type and tissue-specific rates of induced turnover could be achieved using cell-type specific pro-apoptotic small molecule cocktails, peptide mimetics, and/or tissue-tropic AAV-delivered suicide genes driven by cell-type specific promoters. Because these sites of ablation would still be “fresh” when replacement cells are administered, the presumption is that the patterns of ablation will make administered cells more likely to engraft where they should, in freshly vacated niches where the signals promoting cell migration and engraftment are still active. By varying the dose of cell-type targeted ablative agents, cell type and tissue-specific rates of induced turnover could be achieved, allowing for the rate and spatial distribution of turnover to be tuned to the size of the tissue in order to avoid ablating too many cells at once and inadvertently inducing acute tissue failure.

“Cell therapies are limited by low levels of engraftment, and in principle their ability to improve clinical outcomes is limited by the fact that they can only engraft at locations of existing cell loss. Conversely, therapeutic tissue and organ engineering requires surgery, is more likely to introduce biochemical and mechanical abnormalities to tissue ultrastructure through the decellularization process, and is fundamentally incapable of replacing distributed tissues and structures with a high degree of interconnectivity to other tissues in the body. The aim of ICT is to form a bridge between these two main pillars of regenerative medicine, extending the efficacy of cell therapies beyond a patch for existing cell loss and accomplishing the aim of tissue and organ engineering (i.e. the replacement and regeneration of whole tissues and organs) while potentially remaining free of some of their present limitations,” said Giovanni Santostasi, co-author on the paper and a researcher at the Feinberg School of Medicine, Northwestern University.

While future iterations of the therapy could use patient-derived cells, such as ESCs derived via somatic cell nuclear transfer (SCNT) or iPSCs derived from nuclear reprogramming, shorter-term applications would likely use existing stem cell lines immunologically matched to the patient via HLA matching. The authors contend that the cloning of adult organisms with normal lifespans from adult somatic cells testifies to the fact that adult cells can be rejuvenated and used to produce a sufficient quantity of daughter cells to replace the sum of cells constituting adult organisms, and that serial cloning experiments (in which this process is done iteratively, using an adult cell of each subsequent generation to derive the next) attests to this fact even more strongly.

“ICT could theoretically enable the controlled turnover and rejuvenation of aged tissues. The technique is particularly applicable to tissues that are not amenable to growth ex vivo and implantation (as with solid organs) – such as the vascular, lymphatic, and nervous systems. The method relies upon targeted ablation of old, damaged and/or senescent cells, coupled with a titrated replacement with patient-derived semi-differentiated stem and progenitor cells. By gradually replacing the old cells with new cells, entire tissues can be replaced in situ. The body naturally turns over tissues, but not all tissues and perhaps not optimally. I am reminded of the quote attributed to Heraclitus: ‘No man ever steps in the same river twice, for it’s not the same river and he’s not the same man,'” said Sebastian Aguiar, a coauthor on the paper and researcher at the Swammerdam Institute of Life Sciences, University of Amsterdam.

“Reversing aging in humans will require a multi-step approach at multiple levels of the organismal organization. In situ targeted ablation of the senescent cells and regeneration will be an important component of comprehensive anti-aging therapies,” said Alex Zhavoronkov, Chief Science Officer of the Biogerontology Research Foundation.

The researchers originally proposed ICT in 2016 in the context of biomedical gerontology as a possible means of preventing and/or negating age-related phenotypic deviation for the purposes of healthspan extension, and in this new paper they refine the methodological underpinnings of the approach, take a closer look at potential complications and strategies for their deterrence, and analyze ICT in the context of regenerative medicine as an intervention for a broader range of conditions based on disease or dysfunction at the cellular and intercellular level, with potential utilities absent from traditional cell therapies and tissue/organ engineering, the two main pillars of regenerative medicine. The intervention is still very much conceptual, and any potential utilities over other therapeutic modalities within regenerative medicine would need to be verified via preclinical studies, but their hope is to stimulate further research at this interface between geroscience and regenerative medicine.

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The paper is available here.

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.