Patrice Ayme's Thoughts

CURING AGING Will Also CURE US From THERMONUCLEAR WAR TENDENCIES: CRISPR To The RESCUE Of WISDOM!

One can always dream… Aging is not just a problem for hedonists. It is a philosophical problem too, because it hurts the quality of our wisdom, as a civilization, and as individuals, not just the elasticity of our tissues.

Aging means spending, in the best case, one’s last 40 years of one’s life being increasingly assaulted by all sorts of ailments, diseases, and degeneracies. Some youth will scoff, suggest coolly to the old to stop whining, get out-of-the-way, and.  Just die, time is up. And just there lays an obvious problem: aging entices those in la force de l’age to show contempt for life. Worse, even more for the youth, who may feel entitled to fully dehumanize the old, not realizing that, quite soon, they will be old to. And that dehumanization of humans brings alienation, then war.

Moreover, the old have the powers: they spent a lifetime gathering them. And here they are, wounded… by life. Now then they see some youth looking down on them. What do fierce predators do when feeling threatened, wounded and suffering? They lash out. And no predator is more ferocious than man.

Thus aging is a political problem, because it causes resentment, and the will to inflict pain… by those who have the power. Contempt from the youth, impatience in the middle age… And, even deeper than all this, aging, perceived as an insult, brings a contempt for life.

Mother with her progeria afflicted child. Progeria causes baldness, bad skin and membranes aged, all over. Death used to happen by age 13, from heart failure. Now there are partial treatments. CRISP R gives the hope of definitive treatment.

Once I told my 5-year-old daughter, that, as if she wouldn’t accomplish some particular task, she would deprived of something else I knew she wanted. She replied with an old gun fighter smirk “OK, go ahead!” (She has since used this tactic so many times, I had to complexify my sordid ways) Humanity is the same with life, as this little child with her big bad parent. As life threatens to withdraw the love, humanity retorts that life ain’t worth as much as it thinks.

Threatened with the ultimate, the extinction of life, humanity has opted to cordially despise it… As if life itself was lesser than the will of the human spirit to dispose of it. This will to play god, is a deep source of strife.  

Human life is very short, if one compares it to how much there is to learn. After a few decades, much more wisdom has been accumulated in an individual than after two (when typically young people, generally males are most indoctrinable to go out to kill the multitudes for no good reason). These treasures of wisdom get killed by aging and death. Human existence was always a balance between living long to increase wisdom and knowledge, and the necessity to have as many generations as possible.   

Animals age. Because, to improve the species through natural selection, they need generations. Species harvest haphazard (20 C genetics), and, or directed (Lamarck and 21C epigenetics) mutations to evolve. And evolving they need, because of competition with others (hell is others), or the elements (natural disasters).

As the wisdom necessary and other circumstances of a species vary so does its optimal aging. Thus some whales live centuries (although, up to a few years ago, a human-like lifespan had been attributed to them… without checking!). Huge and scary sharks of the Arctic are suspected to live five centuries… (These long lives mean those animals are much more threatened with extinction than thought prior: their replacement rate is a very small fraction of that of a chimpanzee, say.)

Aging animals are sick. Predators press in, and finish by devouring the sick. This, since times immemorial. That elimination of the old, a natural occurrence, has got to be anchored in our psychobiology. The older the populations get, the more sick they get… And thus, deep down inside, evolution whispers that we are sick, degenerate, would be better off, eliminated, all together. Entire nations, led by Japan, followed by Europe, and even the USA and China, are also aging. Thus they invite the ultimate solution to senescence (senescence has a precise meaning in histology; typically stem cells which can’t die, or divide, and are greatly dysfunctional). Weakness itself invites violence. (A little truth the sheep don’t like to hear.)

When a species around a star reaches the thermonuclear stage in civilization, all out competition, that is, all out war, will have consequences which are too drastic… And an ecological crisis, as we have one now will precipitate it. One can’t put thermonuclear power, in the hand of youth, and hope for the best: no all youth is as well-travelled and educated in all sorts of ways as Trump’s interlocutor, Kim of North Korea.

A few years back, a trio of women at UC Berkeley, one from Hawai’i, another from Paris, discovered a radically new and much easier way to engineer DNA. Yes, let’s reassure those who are prize obsessed: Jennifer Doudna and Emmanuelle Charpentier will get the Nobel for discovering “CRISPR”. So much for the alleged woman intellectual inferiority long claimed by sexist males in what even the prestigious science magazine Nature now rightly calls “neurosexism“.

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CRISPR/Cas9 therapy can suppress aging, enhance health and extend life span in mice (18 February, 2019).

Researchers have developed a new gene therapy to decelerate the aging process (at least in a made-up pathological condition similar to progeria in humans). The findings highlight a novel CRISPR/Cas9 genome-editing therapy that can suppress the accelerated aging observed in mice with Hutchinson-Gilford progeria syndrome, a rare genetic disorder that also afflicts humans.Two mice of the same age with progeria. The larger and healthier mouse on the left received the gene therapy, while the mouse on the right did not.

Aging, “the time-related deterioration of the physiological functions necessary for survival and fertility”
is the leading cause for a cornucopia of debilitating conditions, including heart disease, cancer, fibrosis, arthritis, general decomposition and Alzheimer’s disease. This makes the need for anti-aging therapies all the more urgent as the likes of everybody are aging ever more… especially in leading countries, which are suffering a youth population deficit caused by traditional plutocracy.

Now, Salk Institute researchers have developed a new gene therapy to decelerate the aging process.

The findings, published on February 18, 2019 in the journal Nature Medicine, highlight a novel CRISPR/Cas9 genome-editing therapy that can suppress the accelerated aging observed in mice with Hutchinson-Gilford progeria syndrome, a rare genetic disorder that also afflicts humans (and is also known as progeria). This treatment provides important insight into the molecular pathways involved in accelerated aging, as well as how to reduce toxic proteins via gene therapy.

“Aging is a complex process in which cells start to lose their functionality, so it is critical for us to find effective ways to study the molecular drivers of aging,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and senior author of the paper. “Progeria is an ideal aging model because it allows us to devise an intervention, refine it and test it again quickly.“

With an early onset and fast progression, progeria is one of the most severe forms of a group of degenerative disorders caused by a mutation in the LMNA gene. Both mice and humans with progeria show many signs of aging, including DNA damage, cardiac dysfunction and dramatically shortened life span. Humans with progeria seem to age seven (7) years annually. They tend to die of heart disease by the age of 13 to 14 (recently though, one of them, an Italian science student reached 24). The LMNA gene normally produces two similar proteins inside a cell: lamin A and lamin C. Progeria shifts the production of lamin A to progerin. Progerin is a shortened, toxic form of lamin A that accumulates with age and is exacerbated in those with progeria.

“Our goal was to diminish the toxicity from the mutation of the LMNA gene that leads to accumulation of progerin inside the cell,” says co-first author Hsin-Kai Liao, a staff researcher in the Izpisua Belmonte lab. “We reasoned that progeria could be treated by CRISPR/Cas9-targeted disruption of both lamin A and progerin.”

The researchers utilized the CRISPR/Cas9 system to deliver the gene therapy into the cells of the progeria mouse model expressing Cas9. An adeno-associated virus (AAV) was injected containing two synthetic guide RNAs and a reporter gene. The guide RNA ushers the Cas9 protein to a specific location on the DNA where it can make a cut to render lamin A and progerin nonfunctional, without disrupting lamin C. The reporter helps researchers track the tissues that were infected with the AAV.

Two months after the delivery of the therapy, the mice were stronger and more active, with improved cardiovascular health. They showed decreased degeneration of a major arterial blood vessel and delayed onset of bradycardia (an abnormally slow heart rate) — two issues commonly observed in progeria and old age. Overall, the treated progeria mice had activity levels similar to normal mice, and their life span increased by roughly 25 percent.

“Once we improve the efficiency of our viruses to infect a wide range of tissues, we are confident that we will be able to increase life span further,” says Pradeep Reddy, a postdoctoral fellow in the Izpisua Belmonte lab and an author of the paper.

Taken together, the results suggest that targeting lamin A and progerin using a CRISPR/Cas9 system can dramatically improve the physiological health and life span of progeria mice. These results provide a significant new understanding of how scientists may eventually be able to target molecular drivers of aging in humans.

Future efforts will focus on making the therapy more effective and will refine it for human use. Currently, there is no cure for progeria, so the symptoms are managed and complications are treated as they arise.

“This is the first time a gene editing therapy has been applied to treat progeria syndrome,” says Izpisua Belmonte, holder of the Roger Guillemin Chair at Salk. “It will need some refinements, but it has far fewer negative effects compared to other options available. This is an exciting advancement for the treatment of progeria.”

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The preceding is new news, but Crisp was used to correct cataract in mice, already 6 years ago. CrispR is being tested in a so-called “gene drive” on mosquitoes. Inside a lab in Italy for now. The idea is to release a mutation which is inherited in the mosquito population, devastating it. Even the Bible doesn’t have a massacre that divine.

The females become a bit more male, becoming kind of hermaphrodites. While genetically female, the transformed insects have mouths that resemble male mosquito mouths. That means they can’t bite and so can’t spread the malaria parasite. In addition, the insects’ reproductive organs are deformed, which means they can’t lay eggs.

As more and more female mosquitoes inherit two copies of the modification, more and more become sterile.

The plot is that if these modified mosquitoes are eventually shown to be somewhat safe and effective, they may be released in African regions plagued by malaria. The hope is that they would spread their mutation and eventually sterilize all the females. That should crash — or drastically reduce — local populations of the main species of mosquito that spreads malaria, the notorious Anopheles gambiae. Malaria is a huge problem affecting probably two-thirds of the world’s population, and it kills millions every year, in spite of huge efforts. It’s also debilitating and treatments to treat the disease are increasingly ineffective, while presenting their own problems.

So the future is here: mastering genetics, to further our developing divine powers. Animals are quantum machines, intelligently designed by our creator, biological evolution… Indeed, as crown of creation, we are even smarter than our create… And now not just recreate, but self create. Let’s hope we can rise to the occasion, and that the object which zoomed through the solar system was not a spying solar sail sent from the Dark Forest.

Silly? No. For the first time since their last war, nearly half a century ago, 12 French made Indian Mirage fighter-bombers streaked 50 kilometers deep in the mountains of the Karakorum, north Pakistan, and bombed, using laser guidance, a Madrassa, a religious Muslim school, indoctrinating for Jihad. This was in retaliation for a deadly Jihadist bombing of dozens of troops in Kashmir. Indians said they killed 300 Jihadists, Pakistan scoffs that only trees died. However, Pakistan seems to care about trees, as the next day saw Pakistani jets attack India, and an Indian Mig 21 jet, and a Pakistani jet, or two, shot down. This is a rare case of deliberate attacks between nuclear armed states. But then, India had been attacked. India is a representative democracy… Pakistan is officially a religious state, and more precisely an “Islamic” one, thus a fascist dictatorship.

Fascist religions have, deep down inside, been established to forget about aging, and the pains it brings. If Pakistani leaders had 1,000 years of life to lose, they would be more careful, before playing thermonuclear clowns.

Patrice Ayme

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