Tag Archives: DNA


Aubrey de Grey at the Launching Longevity Panel, and Announcing Acceptance of the First Paper to be Published on MitoSENS Research – Article by Reason

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The New Renaissance HatReason

Today I’ll direct your attention to a couple of videos, thematically linked by the presence of Aubrey de Grey, cofounder of the SENS Research Foundation and tireless advocate for progress towards working rejuvenation therapies. For the first of the videos, de Grey recently took part in a panel discussion involving representatives of the biotechnology industry, the research establishment, and venture capital community, with the topic being the coming development of a new industry that will develop therapies to extend healthy life and turn back aging. That industry has barely started to form its earliest and smallest stage today, as the first lines of rejuvenation research reach the point of commercial viability. There are a few startups and a lot of deep pockets yet to be convinced that this is going somewhere – though the commentary in the panel is encouraged, considering those involved.

The recent Rejuvenation Biotechnology 2016 conference hosted by the SENS Research Foundation was more along the same lines, focused on creating a foundation for the near future industry that will build and provide rejuvenation therapies. The purpose of the conference series is to help smooth the way for these treatments to move rapidly from the laboratory to the clinic, to build the necessary relationships, manage expectations, and pull in the additional support needed to make best possible progress. The conference was livestreamed over the past couple of days, and at one point Aubrey de Grey announced the just-then-and-there acceptance of the first scientific publication for the MitoSENS team at the SENS Research Foundation. They are presently in the lead, at the cutting edge, among the few groups working on the project of copying mitochondrial genes into the cell nucleus to protect them from the damage of aging. Ultimately, copying all thirteen genes should completely remove the contribution of mitochondrial damage to degenerative aging, as mitochondria will no longer become dysfunctional as their local DNA is damaged. They will get the proteins they need from the cell nucleus instead. It is a worthy project, and it is always welcome to see progress on this front.

Launching Longevity: Funding the Fountain of Youth


Can technology make human longevity a reality? As the pace of discovery accelerates, scientists and entrepreneurs are closing in on the Fountain of Youth. Disrupting the aging process by hacking the code of life, promises better health and longer maximum lifespans. With many layers of complexity from science to ethics, there are still skeptics placing odds against human longevity. Venture capitalists are betting on success; putting big money on the table to fund longevity startups. Google/Alphabet and drugmaker AbbVie have invested $1.5 billion on Calico, while Human Longevity Inc. recently raised $220 million from their Series B funding round. Complementing traditional venture investment, VCs like Peter Thiel and Joon Yun have established foundations and prizes to accelerate the end of aging. Why are VCs suddenly investing heavily in longevity startups? Will extended lifespan be a privilege of the wealthy or will the benefits be accessible to all? How long before these well-funded startups bring viable products to market?


Aubrey de Grey Announces Progress in MitoSENS


Ok everybody, before I introduce the next session I just wanted to make a very small, brief, but very welcome announcement. Literally half an hour ago we received some extremely good scientific news. Those of you who have been following SENS research since before the SENS Research Foundation itself even existed will know that, about a decade ago, the very first project, the very first research program that we were able to initiate – with the help of, especially, the initial donation of Peter Thiel – was to make mitochondrial mutations harmless by essentially putting backup copies of the mitochondrial DNA into the nuclear genome, modified in such way of course that the encoded proteins would be colocated back into the mitochondria to do their job. This is an idea that was first put forward more than 30 years ago, but it is an idea that despite quite a bit of initial effort, nobody was able to make work. When I first came across this concept, in fact I’d thought of it myself, it’s a pretty obvious idea really, I came to the conclusion that a lot of the despair and despondency and pessimism about this approach was premature, and that it was worth having another go, and so that was the very first project we decided to fund.

Suffice to say that it has not been quite as easy as I was hoping to make progress in that space, but progress has now been made, step by step, over the past several years, with the help especially of the absolutely amazing team we have at the research center, who work on this, headed by Matthew O’Connor. Amutha Boominathan is the number two on the team, and is absolutely indispensable, I’ve no idea where we’d be without her. So, what’s happened half an hour ago is that for the very first time in the entire history of this project, we have got far enough to have a paper accepted in a very nice journal, Nucleic Acids Research, which reports on our progress in this area. The headline result in this paper is that we are the first team ever to get two of the proteins encoded by genes in the mitochondrial DNA simultaneously functioning in the same cell line, and of course – two is equivalent to infinity for mathematicians, you know that, right? – this is extremely heartening news, and I just wanted to let you all know, thank you.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.
This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.


Towards a Greater Knowledge of Mitochondrial DNA Damage in Aging – Article by Reason

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The New Renaissance HatReason

Today I’ll point out a very readable scientific commentary on mutations in mitochondrial DNA (mtDNA) and the importance of understanding how these mutations spread within cells. This is a topic of some interest within the field of aging research, as mitochondrial damage and loss of function is very clearly important in the aging process. Mitochondria are, among many other things, the power plants of the cell. They are the evolved descendants of symbiotic bacteria, now fully integrated into our biology, and their primary function is to produce chemical energy store molecules, adenosine triphosphate (ATP), that are used to power cellular operations. Hundreds of mitochondria swarm in every cell, destroyed by quality control processes when damaged, and dividing to make up the numbers. They also tend to promiscuously swap component parts among one another, and sometimes fuse together.

Being the descendants of bacteria, mitochondria have their own DNA, distinct from the nuclear DNA that resides in the cell nucleus. This is a tiny remnant of the original, but a very important remnant, as it encodes a number of proteins that are necessary for the correct operation of the primary method of generating ATP. DNA in cells is constantly damaged by haphazard chemical reactions, and equally it is constantly repaired by a range of very efficient mechanisms. Unfortunately mitochondrial DNA isn’t as robustly defended as nuclear DNA. Equally unfortunately, some forms of mutation, such as deletions, seem able to rapidly spread throughout the mitochondrial population of a single cell, even as they make mitochondria malfunction. This means that over time a growing number of cells become overtaken by malfunctioning mitochondria and fall into a state of dysfunction in which they pollute surrounding tissues with reactive molecules. This can, for example, increase the level of oxidized lipids present in the bloodstream, which speeds up the development of atherosclerosis, a leading cause of death at the present time.

The question of how exactly some specific mutations overtake a mitochondrial population so rapidly is still an open one. There is no shortage of sensible theories, for example that it allows mitochondria to replicate more rapidly, or gives them some greater resistance to the processes of quality control that normally cull older, damaged mitochondria. The definitive proof for any one theory has yet to be established, however. In one sense it doesn’t actually matter all that much: there are ways to address this problem through medical technology that don’t require any understanding of how the damage spreads. The SENS Research Foundation, for example, advocates the path of copying mitochondrial genes into the cell nucleus, a gene therapy known as allotopic expression. For so long as the backup genes are generating proteins, and those proteins make it back to the mitochondria, the state of the DNA inside mitochondria doesn’t matter all that much. Everything should still work, and the present contribution of mitochondrial DNA damage to aging and age-related disease would be eliminated. At the present time there are thirteen genes to copy, a couple of which are in commercial development for therapies unrelated to aging, another couple were just this year demonstrated in the lab, and the rest are yet to be done.

Still, the commentary linked below is most interesting if you’d like to know more about the questions surrounding the issue of mitochondrial DNA damage and how it spreads. This is, as noted, a core issue in the aging process. The authors report on recent research on deletion mutations that might sway the debate on how these mutations overtake mitochondrial populations so effectively.

Expanding Our Understanding of mtDNA Deletions

A challenge of mtDNA genetics is the multi-copy nature of the mitochondrial genome in individual cells, such that both normal and mutant mtDNA molecules, including selfish genomes with no advantage for cellular fitness, coexist in a state known as “heteroplasmy.” mtDNA deletions are functionally recessive; high levels of heteroplasmy (more than 60%) are required before a biochemical phenotype appears. In human tissues, we also see a mosaic of cells with respiratory chain deficiency related to different levels of mtDNA deletion. Interestingly, cells with high levels of mtDNA deletions in muscle biopsies show evidence of mitochondrial proliferation, a compensatory mechanism likely triggered by mitochondrial dysfunction. In such circumstances, deleted mtDNA molecules in a given cell will have originated clonally from a single mutant genome. This process is therefore termed “clonal expansion.”

The accumulation of high levels of mtDNA deletions is challenging to explain, especially given that mitophagy should provide quality control to eliminate dysfunctional mitochondria. Studies in human tissues do not allow experimental manipulation, but large-scale mtDNA deletion models in C. elegans have proved to be helpful, showing some conserved characteristics that match the situation in humans, as well as some divergences. Researchers have used a C. elegans strain with a heteroplasmic mtDNA deletion to demonstrate the importance of the mitochondrial unfolded protein response (UPRmt) in allowing clonal expansion of mutant mtDNAs to high heteroplasmy levels. They demonstrate that wild-type mtDNA copy number is tightly regulated, and that the mutant mtDNA molecules hijack endogenous pathways to drive their own replication.

The data suggests that the expansion of mtDNA deletions involves nuclear signaling to upregulate the UPRmt and increase total mtDNA copy number. The nature of the mito-nuclear signal in this C. elegans model may have been the transcription factor ATFS-1 (activating transcription factor associated with stress-1), which fails to be imported by depolarized mitochondria, mediates UPRmt activation by mtDNA deletions. A long-standing hypothesis proposes that deleted mtDNA molecules clonally expand because they replicate more rapidly due to their smaller size. To address this question, researchers examined the behavior of a second, much smaller mtDNA deletion molecule. They found no evidence for a replicative advantage of the smaller genome, and clonal expansion to similar levels as the larger deletion. In human skeletal muscle, mtDNA deletions of different sizes also undergo clonal expansion to the same degree. Furthermore, point mutations that do not change the size of the total mtDNA molecule also successfully expand to deleterious levels, indicating that clonal expansion is not driven by genome size. Thus, similar mechanisms may be operating across organisms. In the worm, this involves mito-nuclear signaling and activation of the UPRmt.

There is some debate over interpretation of results. One paper indicates that UPRmt allows the mutant mtDNA molecules to accumulate by reducing mitophagy. Another demonstrates that the UPRmt induces mitochondrial biogenesis and promotes organelle dynamics (fission and fusion). Both papers show that by downregulating the UPRmt response, mtDNA deletion levels fall, which may allow a therapeutic approach in humans. Could there be a similar mechanism in humans, especially since some features detected in C. elegans are also present in human tissues, including the increase in mitochondrial biogenesis and the lack of relationship between mitochondrial genome size and expansion? It is likely that there will be a similar mechanism to preserve deletions since, as in the worm, deletions persist and accumulate in human tissues, despite an active autophagic quality-control process. Although the UPRmt has not been characterized in humans as it has in the worm, and no equivalent protein to ATFS-1 has been identified in mammals, proteins such as CHOP, HSP-60, ClpP, and mtHSP70 appear to serve similar functions in mammals as those in C. elegans and suggest that a similar mechanism may be present.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.
This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.


G. Stolyarov II Interviews Demian Zivkovic Regarding the D.N.A. – Gene Therapies Congress

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The New Renaissance Hat
G. Stolyarov II and Demian Zivkovic

Mr. Stolyarov invited Demian Zivkovic, President of the Institute of Exponential Sciences (IES), to discuss the forthcoming Designing New Advances (D.N.A.) Gene Therapies Congress in Utrecht, The Netherlands.

The interview took place on Sunday, June 19, 2016, at 11 a.m. US Pacific Time. Watch the recording here.

The D.N.A. Congress is scheduled to occur on July 9, 2016, and will feature speakers such as Oliver Medvedik, Aubrey de Grey, Elizabeth Parrish, Keith Comito, and Tatjana Kochetkova. This event receives the strong endorsement of both The Rational Argumentator and the Nevada Transhumanist Party.

Read the announcement of the D. N. A. Congress here.

Contribute to the fundraiser for the D. N. A. Congress on Indiegogo  and Generosity.

DNA_Interview_CoverDemian Zivkovic is the president of the Institute of Exponential Sciences  (Facebook  / Meetup) – an international transhumanist think tank / education institute comprised of a group of transhumanism-oriented scientists, professionals, students, journalists, and entrepreneurs interested in the interdisciplinary approach to advancing exponential technologies and promoting techno-positive thought. He is also an entrepreneur and student of artificial intelligence and innovation sciences and management at the University of Utrecht.

Demian and the IES have been involved in several endeavors, such as organizing lectures on exponential sciences, interviewing experts such as Aubrey de Grey, joining several of Mr. Stolyarov’s futurism panels, and spreading Death is Wrong – Mr. Stolyarov’s illustrated children’s book on indefinite life extension – in The Netherlands.

Demian Zivkovic is a strong proponent of healthy life extension and cognitive augmentation. His interests include hyperreality, morphological freedom advocacy, postgenderism, and hypermodernism. He is currently working on his ambition of raising enough capital to make a real difference in life extension and transhumanist thought.


D.N.A. Congress Announcement by the Institute of Exponential Sciences

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The New Renaissance HatInstitute of Exponential Sciences

Editor’s Note: The forthcoming D.N.A. Congress in Utrecht, The Netherlands, hosted by the Institute of Exponential Sciences, devoted to discussions of gene therapies, receives the strong endorsement of both The Rational Argumentator and the Nevada Transhumanist Party. The D.N.A. Congress offers a promising venue to discuss the potential for gene therapies to cure diseases, lengthen lifespans, and improve quality of life for millions of people in the coming years and decades.

~ Gennady Stolyarov II, Editor-in-Chief, The Rational Argumentator, June 5, 2016


The Institute of Exponential Sciences (IES) has a large announcement to make. We are organising D.N.A – The largest European congress on human gene therapies, featuring speakers such as Aubrey de Grey, Liz Parrish, Oliver Medvedik and others.

Our event has been endorsed by LEAF, Heales VZW, BioViva, SENS Research Foundation, Singularity Network, People Unlimited, The Rational Argumentator, and many others. The event will be covered by national media and will be broadcasted online.

To make this vision a reality, we need your support. Share this message and donate today. Thank you!

IES needs your support to help make this vision a reality. Click here to donate to our crowdfunding campaign.

D.N.A – Designing New Advances: The second large Institute of Exponential Sciences event is coming to Utrecht


DNADemian Zivkovic

Utrecht – After a successful event last year in May, the grand congress is ready for a second edition. With a new name, we hope to make exponential sciences more approachable to the general public and bring people in the field closer together. The Institute of Exponential Sciences congress 2016 will be held at RASA podium on the 9th of July. The main theme of the event is gene therapies and cutting-edge applications of such therapies, such as health extension and interventions against human aging. To guarantee a great event, we have invited some of the biggest names in the field. Our guest speakers will be as follows:

Opening the event will be Oliver Medvedik, Ph.D, director of scientific programs at Genspace. Dr. Medvedik has earned his Ph.D at Harvard Medical school in the biomedical and biological sciences program. Since graduating from Harvard, he has worked as a biotechnology consultant, taught molecular biology to numerous undergraduates at Harvard, and mentored two of Harvard’s teams for the international genetically engineered machines competition (IGEM) held annually at M.I.T.

Our second speaker is Aubrey David Nicholas Jasper de Grey, Ph.D, an English author, Chief Science Officer of the SENS Research Foundation, and editor-in-chief of the academic journal Rejuvenation Research. Aubrey de Grey is well known for his focus on regenerative medicine and views on human aging. He will take the stage talking about the applications of current and upcoming technologies and studies which hold the potential to greatly extend our healthy lifespan.

Our third speaker is Tatjana Kochetkova, Ph.D, who is a fellow of the Institute of Exponential Sciences and a bioethicist. Dr. Kochetkova will follow up discussing the ethical and philosophical side of the technology and will address questions of what exponential technologies in biotech mean for society.

Our fourth speaker is Elizabeth Parrish, a fellow of the Institute of Exponential Sciences and the Founder and CEO of BioViva Sciences Inc, a Delaware corporation based in Seattle, WA, with labs and participating clinics in South/Central America where the majority of practical work is carried out. BioViva has been noted for being the first corporation in the world to treat a patient with gene therapy to reverse aging. The woman who wants to genetically engineer you will cover the basics of BioViva’s approach and vision for the the future, as well as the potential that gene therapies hold for radically improving our health and lives in the future.

Our fifth speaker will be Keith Comito, who is the founder and president of the Life Extension Advocacy Foundation (LEAF), a 501(c)(3) non-profit organization and a partner of the Institute of Exponential Sciences. Through LEAF, he operates the crowdfunding platform Lifespan.io, which supports biomedical research aimed at extending healthy human lifespan. He also serves as policy coordinator for the Global Healthspan Policy Institute, which facilitates relationships between researchers and government to advance initiatives in support of healthy life extension.

About Institute of Exponential Sciences

The Institute of Exponential Sciences is an international innovation-oriented think tank, outreach organisation, and networking platform based in the Netherlands, in the city of Utrecht. Its main activities include organising lectures and conferences, providing quality consultancy on innovation and exponential technologies, and collaborating with student organisations and universities in educating the public on the importance of exponential technologies.

It was founded by members of its predecessor, the Arma’thwynn society, which was a student group of like-minded young academics in the Netherlands. After organising events and attracting a very diverse and professional team of entrepreneurs, academics, and journalists, the society decided to move past student politics and make the move towards professionalism.

The Institute of Exponential Sciences is the result of that decision. After organising successful events (the largest of which was their symposium in April, 2015), the Institute of Exponential Sciences formalised its mission and reached out towards a process of international collaboration with other entities which share a techno-positive vision. The institute strives towards excellence in providing the best information and resources related to the issues relevant in the rapidly advancing technological society we live in.

The IES approach is focused on providing interdisciplinary education in the fields of exponential technologies such as artificial intelligence, bio-informatics, gene therapies, 3D-printing, augmented reality, and neural interfacing. We also provide a networking platform which allows entrepreneurs, scientists, journalists, and students to get in touch with others with similar ideas so that they may create the technologies of tomorrow. The IES strives not only to improve the speed of development of these technologies, but also to show the public the amazing possibilities technology provides for society.

IES and the IES logo are either registered trademarks or trademarks of IES Foundation in the Netherlands and/or other countries. All other products and/or services referenced are trademarks of their respective entities.


Will Banning Genetic Engineering Kill You? – Article by Edward Hudgins

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The New Renaissance HatEdward Hudgins

One headline reads “British baby given genetically-edited immune cells to beat cancer in world first.” Another headline reads “Top biologists debate ban on gene-editing.” It’s a literal life-and-death debate.

And if you care to live, pay attention to this philosophical clash!

Exponential growth in genetic engineering

Genetic engineering is on an exponential growth path. In 2001 the cost of sequencing a human-sized genome was about $100 million. By 2007 the cost was down to $10 million.

layla-richard-genetic-engineeringNow it’s just over $1,000. Scientists and even do-it-yourself biohackers can now cheaply access DNA information that could allow them to discover cures for diseases and much more.

Recently, for example, baby Layla Richards [at right] was diagnosed with leukemia. But when none of the usual treatments worked, doctors created designer immune cells, injected them into the little girl and the treatment worked. She was cured.

Designer babies?

But there have been concerns about such engineering for decades; indeed, precautionary guidelines were drawn up by a group of biologists at the 1975 Asilomar conference in California. And now, at a joint conference in Washington, D.C. of the National Academies of Medicine and Sciences, the Chinese Academy of Sciences and the Royal Society of the United Kingdom, a cutting-edge genetic engineering tool known as CRISPR-Cas9 came under attack because it can be used to edit the genomes of sperm, eggs, and embryos.

National Institutes of Health director Francis Collins argued that the children that would result from such editing “can’t give consent to having their genomes altered” and that “the individuals whose lives are potentially affected by germline manipulation could extend many generations into the future.” Hille Haker, a Catholic theologian from Loyola University Chicago, agreed and proposed a two year ban on all research into such manipulation of genomes. Others argued that such manipulation could lead to “designer babies,” that is, parents using this technology to improve or enhance the intelligence and strength of their children.

These arguments are bizarre to say the least.

Damning to misery

To begin with, there is virtual universal agreement among religious and secular folk alike that from birth and until a stage of maturity at which they can potentially guide their lives by their own reason, the consent of children is not needed when their parents make many potentially life-altering decisions for them. Why should this reasonable rule be different for decisions made by parents before a child is born?

And consider that the principal decisions with gene-editing technology would be to eliminate the possibility of the child later in life having Alzheimer’s or Parkinson’s diseases, cancers, and a host of other ailments that plague humanity. Is it even conceivable that any rational individual would not thank their parents for ensuring their health and longevity? Isn’t this what all parents wish for their children? Why would anyone deny parents the tools to ensure healthy children? How much continued misery and death are those who would delay genetic research or ban this new technology inflicting on parents and children alike?

And so what if the “slippery slope” is parents ensuring that their children are more intelligent or stronger? Right now such traits are a matter of a genetic lottery and every parent hopes for the best. What parent wouldn’t jump at the chance to ensure such beneficial capacities for their children?

A privileged biological elite?

Some might pull out the ugly egalitarian argument that the “rich” could produce biologically elite “superchildren,” leaving the rest of humanity behind: an inferior, impoverished breed to be exploited. But this is the same spurious argument made about every technology that initially allows more prosperous individuals to better themselves ahead of others. We heard two decades ago that only the “rich” would be able to afford computers and the internet, allowing them to be more informed and, thus, enabling them to oppress the downtrodden masses. But exponential changes in technologies ensure that just as computers and the internet have become inexpensive and available to all, so will genetic enhancements become after the techniques are perfected for prosperous beta-testers.

And in any case, just as it is immoral to deprive those who honestly earn their wealth of the fruits of their labor just because others have yet to earn theirs, so it is immoral to deprive them of the opportunity to provide the best biology for their children just because it will take time for the technology to become available to all.

Precautionary principle or proactionary principle?

Many opponents of genetic engineering fall back on the so-called “precautionary principle.” This is the notion that if products or technologies pose any imaginable risks—often highly speculative or vague ones unsupported by any sound science—then such products or technologies should be severely restricted, regulated, or banned. The burden is placed on innovators to prove that no harm to humans will result from their innovations.

But had this standard been applied in the past, we would not have the modern world today. Indeed, by this standard, precaution would dictate that fire was just too dangerous for humans and that cavemen should have been barred from rubbing two sticks together.

Max More, a founder of the transhumanist philosophy, offers instead the “proactionary principle.” He argues that “People’s freedom to innovate technologically is highly valuable, even critical, to humanity.” And “Progress should not bow to fear, but should proceed with eyes wide open.” And that we need to “Protect the freedom to innovate and progress while thinking and planning intelligently for collateral effects.”

Freedom to progress

Fortunately, more individuals than More reason this way. At the D.C. conference, University of Manchester Professor John Harris argued “We all have an inescapable moral duty: To continue with scientific investigation to the point at which we can make a rational choice. We are not yet at that point. It seems to me, consideration of a moratorium is the wrong course. Research is necessary.” But the opinion of academics one way or another might not matter. Just as it was do-it-yourselfers and innovators in garages that made the computer and information revolution, genetic innovations might well come from such achievers as well. But they won’t do it if they are not free to do so.

If you value your life and the lives and health of your children, you had better work for this freedom to innovate.

Dr. Edward Hudgins directs advocacy and is a senior scholar for The Atlas Society, the center for Objectivism in Washington, D.C.

Copyright The Atlas Society. For more information, please visit www.atlassociety.org.


Lifespan Challenge: Support the MitoSENS Mitochondrial Repair Project Research Fundraiser – Video by G. Stolyarov II

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The New Renaissance HatG. Stolyarov II
October 21, 2015

Mr. Stolyarov, author of “Death is Wrong” and Chief Executive of the Nevada Transhumanist Party (NTP), challenges all members of the NTP and the general public to donate to life-extension research – particularly, the ongoing MitoSENS Mitochondrial Repair Project for which crowdfunding is currently being conducted on Lifespan.io.



MitoSENS Mitochondrial Repair Project Description
Updates and Stretch Goals for the MitoSENS Mitochondrial Repair Project
SENS Research Foundation
– “The #LifespanChallenge Starting on October 1 – International Longevity Day” – Article by Keith Comito
Death is Wrong – Official Home Page
Nevada Transhumanist Party – Constitution and Bylaws
Nevada Transhumanist Party – Facebook Page


Malaria, Sickle-Cell Anemia, and Natural Selection (2003) – Article by G. Stolyarov II

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The New Renaissance Hat
G. Stolyarov II
July 26, 2014
Note from the Author: This essay was originally written in 2003 and published on Associated Content (subsequently, Yahoo! Voices) in 2007.  The essay earned over 13,000 page views on Associated Content/Yahoo! Voices, and I seek to preserve it as a valuable resource for readers, subsequent to the imminent closure of Yahoo! Voices. Therefore, this essay is being published directly on The Rational Argumentator for the first time.  ***
~ G. Stolyarov II, July 26, 2014

The Genetics Behind the Survival of Sickle-Cell Disease


This paper explores the genetics behind malaria and sickle-cell anemia, a fascinating case where the presence of an allele for sickle-cell anemia prevents individuals from getting malaria. This effect explains the presence of some natural selection in favor of the sickle-cell anemia allele.

Alternative versions of a gene are alleles. Each gene resides at a specific chromosome locus. The DNA at that locus, however, can vary somewhat in sequence of nucleotides and information content. Alleles are these possible DNA variations.

Individuals who are homozygous for an allele have both alleles of the same sort, one on each pertinent locus of two homologous chromosomes. Individuals who are heterozygous for an allele have two different alleles, one on each of the homologous chromosomes.

Natural selection through differential reproductive success can cause allele frequencies in a population to change. Disasters or dramatic changes in the environment can also bring about a bottleneck effect whereby the small quantity of individuals remaining does not statistically represent the former population. Thus, the available gene pool has been altered dramatically.

Malaria is a tropical disease transmitted through the bite of a mosquito. The malarial protozoa infect the liver and reproduce, subsequently infecting the victim’s red blood cells and becoming available for transfer to other individuals via another mosquito.

People in Africa or of African descent often carry the sickle-cell anemia allele because heterozygotes for the allele can be protected from malaria while not exhibiting considerable symptoms of sickle-cell anemia. They can survive to reproductive age and transfer the allele to offspring, thus perpetuating the allele’s occurrence in the gene pool.

Natural selection can serve as a mechanism for the survival in heterozygotes of certain recessive alleles which pose great harm to recessive homozygotes. If the allele confers an advantage to a heterozygote that is lacked by the dominant homozygote (which in this case is vulnerable to malaria), this allele can be spread to future generations, since its carriers reach reproductive age with greater likelihood. In a different environment, however, where malaria does not occur frequently or at all, there will be little or no survival advantage from being a carrier of the sickle-cell allele. Although these individuals can still reproduce without great obstacles, they are no longer favored over the homozygous dominant genotype. Thus, in places such as the United States, the sickle-cell allele is not nearly as frequent as in the tropical regions of Africa. Nevertheless, it does occur in a very small percentage of the population of African descent, seeing as insufficient time has passed in order for the allele frequency to decline to negligible amounts.

One of the reasons why sickle-cell disease can still potentially exist in malaria-free environments is the fact that heterozygotes’ normal phenotypes “mask” the existence of the allele within their genotypes. Thus, they can mate with healthy heterozygote partners and produce diseased offspring. Perhaps technological advancement in the near future will enable individuals to learn of their own genotypes and the possibility of transferring such diseases to their children, thus enabling them to make more prudent decisions concerning reproduction. Heterozygotes may choose to marry dominant homozygotes in the United States, or clone themselves in Africa so as to ensure that malaria resistance will be passed to their children without the risk of them acquiring sickle-cell disease.

Yet natural selection does not always function in a perfect or desirable manner. In many experimental cases, introducing just one heterozygote into an area with high rates of malaria death failed to establish the sickle-cell allele. Many factors can account for this, including the possibility that the heterozygote did not transfer the recessive allele to his offspring, or that he died of a cause absolutely unrelated to malaria or sickle-cell anemia prior to transferring the allele to offspring.


Weak Evidence Against a Significant Role for Nuclear DNA Damage in Aging – Article by Reason

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The New Renaissance Hat
February 2, 2014
Recommend this page.

The nuclear DNA in our cells is surrounded by a panoply of exceedingly efficient quality control and repair machinery, but nonetheless damage occurs: individual cells suffer all sorts of mutations over time as molecules react with DNA or pieces are lost or reshuffled during replication. This is more pronounced in long-lived cells, such as those in the central nervous system, or the stem cell populations that support specific tissues.

Cancer spawns from nuclear DNA damage, and the risk of cancer grows greatly with age – not just because of growing damage to nuclear DNA, but also due to the decline of the immune system’s watchdogs and other related consequences of aging. But aside from cancer, does the accumulation of various forms of nuclear DNA damage scattered across our cells contribute meaningfully to dysfunction and decline? There is some debate on this topic, and while the consensus position is more or less “yes, of course,” there is at this point no experiment by which one can conclusively demonstrate that this is the case.

Today I’ll point you to an open-access study in which researchers compare DNA sequencing data from the blood of a pair of 40-year-old twins and a pair of 100-year old twins. Blood cells cycle into and out of circulation on a timescale of a few months, but we might take nuclear DNA damage in blood cells as being representative of the damage present in the population of hematopoietic stem cells that generated those blood cells.

Aging as Accelerated Accumulation of Somatic Variants: Whole-Genome Sequencing of Centenarian and Middle-Aged Monozygotic Twin Pairs


It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories.In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing.

We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood.

I would have expected more differences and larger differences to turn up, but, as the researchers note, it is impossible to detect mutations that have not spread to at least some degree. (In this case, that means spreading through the population of hematopoietic stem cells.) A next step might be a survey of whole-genome sequencing by tissue types in old twins, especially those with longer-lived cells, to see whether this low level of exhibited mutational damage is peculiar to blood or typical for most or all tissues.


The number of somatic variants may be substantially larger but those present in smaller fractions of cells go undetected. Consistent, detectable somatic variation likely includes somatic mosaicism in blood generated during development or clonal expansion of mutations generated at any point during the lifetime. The frequency of these variants is limited in blood even after 100 years of life. In summary, this study shows that the number of detectable somatic variants in blood by using NGS is very low and that accumulation of somatic mutations is not necessarily a consequence of a century of life. Stochastic somatic variation occurring in less than 20% of cells will go undetected, however.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.