Here’s a tantalizing bit of gene research. Scientists were able to switch off a central gene in the nucleus of a mouse cell. That in turn meant the mouse’s mitochondria started failing (I’m going to be talking a lot more about these fascinating bits of machinery in our cells). After two months, the poor lab mice were wrinkled, going bald and their organs were aging rapidly, but lo, after the gene in the nucleus was switched on again, the mitochondria were restored, and wow, all the hair and skin grew back to what it had been before.
Mitochondria have their own DNA loops.
Why get excited about mitochondria? These are tiny biological batteries we have inside every cell. The are the mini-factories burning sugar or fat, generating free radicals on a mass scale and churning out the chemical energy that is then used in most of the chemical reactions in our body. They are turning up in every second paper these days related to aging. These little organelles are so important and rule breaking they even have their own DNA loops with 37 genes — this is the only genetic material in us that is not part of the Big 23 Chromosomes.
What this means? Specifically, we can cure one type of artificial aging in rodents. It’s possible this tells us something very significant about our own aging bodies, but it’s also possible we may go bald and wrinkled for other reasons (or multiple reasons simultaneously). It also may not be safe to play games with this gene. But we’ve learnt something that’s important. If we can slow aging itself we also slow all the diseases of aging — cognitive decline, cancer, heart disease, stroke. Mostly we tackle the symptoms of aging, not aging itself. That’s what makes this research so interesting.
As I’ve been saying for twenty years, within all our cells are the same genes that we had when we were young. If we can figure out how to switch on the right ones at the right time, and correct errors, in theory we can restore body parts from within using our own genes. That’s when everything changes. — Jo
The Sun:
“This mouse model should provide an unprecedented opportunity for the development of preventive and therapeutic drug development strategies to augment the mitochondrial functions for the treatment of ageing-associated skin and hair pathology and other human diseases in which mitochondrial dysfunction plays a significant role.
“It suggests that epigenetic mechanisms underlying mitochondria-to-nucleus cross-talk must play an important role in the restoration of normal skin and hair phenotype.”
In other words, the research suggests the mitochondria plays an important role in the ageing process and should be investigated further to determine new ways of reversing ageing.
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Scientists reverse aging-associated skin wrinkles and hair loss in a mouse model
A gene mutation causes wrinkled skin and hair loss; turning off that mutation restores the mouse to normal appearance.
Researchers have reversed wrinkled skin and hair loss, hallmarks of aging, in a mouse model. When a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and extensive, visible hair loss in a matter of weeks. When the mitochondrial function is restored by turning off the gene responsible for mitochondrial dysfunction, the mouse returns to smooth skin and thick fur, indistinguishable from a healthy mouse of the same age.
The same mouse, left to right — before treatment, then after mitochondrial function was switched down for two months, then finally one month later after mitochondrial function was restored. Credit UAB.
Wrinkled skin and hair loss are hallmarks of aging. What if they could be reversed?
Keshav Singh, Ph.D., and colleagues have done just that, in a mouse model developed at the University of Alabama at Birmingham. When a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and extensive, visible hair loss in a matter of weeks. When the mitochondrial function is restored by turning off the gene responsible for mitochondrial dysfunction, the mouse returns to smooth skin and thick fur, indistinguishable from a healthy mouse of the same age.
“To our knowledge, this observation is unprecedented,” said Singh, a professor of genetics in the UAB School of Medicine.
Importantly, the mutation that does this is in a nuclear gene affecting mitochondrial function, the tiny organelles known as the powerhouses of the cells. Numerous mitochondria in cells produce 90 percent of the chemical energy cells need to survive.
In humans, a decline in mitochondrial function is seen during aging, and mitochondrial dysfunction can drive age-related diseases. A depletion of the DNA in mitochondria is also implicated in human mitochondrial diseases, cardiovascular disease, diabetes, age-associated neurological disorders and cancer.
“This mouse model,” Singh said, “should provide an unprecedented opportunity for the development of preventive and therapeutic drug development strategies to augment the mitochondrial functions for the treatment of aging-associated skin and hair pathology and other human diseases in which mitochondrial dysfunction plays a significant role.”
The mutation in the mouse model is induced when the antibiotic doxycycline is added to the food or drinking water. This causes depletion of mitochondrial DNA because the enzyme to replicate the DNA becomes inactive.
In four weeks, the mice showed gray hair, reduced hair density, hair loss, slowed movements and lethargy, changes that are reminiscent of natural aging. Wrinkled skin was seen four to eight weeks after induction of the mutation, and females had more severe skin wrinkles than males.
Dramatically, this hair loss and wrinkled skin could be reversed by turning off the mutation. The photos below show the hair loss and wrinkled skin after two months of doxycycline induction, and the same mouse a month later after doxycycline was stopped, allowing restoration of the depleted mitochondrial DNA.
Little change was seen in other organs when the mutation was induced, suggesting an important role for mitochondria in skin compared to other tissues.
The wrinkled skin showed changes similar to those seen in both intrinsic and extrinsic aging — intrinsic aging is the natural process of aging, and extrinsic aging is the effect of external factors that influence aging, such as skin wrinkles that develop from excess sun or long-term smoking.
Among the details, the skin of induced-mutation mice showed increased numbers of skin cells, abnormal thickening of the outer layer, dysfunctional hair follicles and increased inflammation that appeared to contribute to skin pathology. These are similar to extrinsic aging of the skin in humans. The mice with depleted mitochondrial DNA also showed changed expression of four aging-associated markers in cells, similar to intrinsic aging.
The skin also showed disruption in the balance between matrix metalloproteinase enzymes and their tissue-specific inhibitor — a balance of these two is necessary to maintain the collagen fibers in the skin that prevent wrinkling.
The mitochondria of induced-mutation mice had reduced mitochondrial DNA content, altered mitochondrial gene expression, and instability of the large complexes in mitochondria that are involved in oxidative phosphorylation.
Reversal of the mutation restored mitochondrial function, as well as the skin and hair pathology. This showed that mitochondria are reversible regulators of skin aging and loss of hair, an observation that Singh calls “surprising.”
“It suggests that epigenetic mechanisms underlying mitochondria-to-nucleus cross-talk must play an important role in the restoration of normal skin and hair phenotype,” Singh said, who has a secondary UAB appointment as professor of pathology. “Further experiments are required to determine whether phenotypic changes in other organs can also be reversed to wildtype level by restoration of mitochondrial DNA.”
REFERENCE:
Singh et al. (2018) Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function. Cell Death & Disease, 2018; 9 (7) DOI: 10.1038/s41419-018-0765-9
*Why this story? My honours was in genetic research. I used to do keynote speeches on aging, medical research and how we will break annuity tables and predictions of lifespans as the benefits of the gene revolution start to pay off. I’ve been following these medical stories for years. It’s time for the blog to branch out into other scientific and political areas. Anything that I think readers will be interested in. There is a transformation going on in medical research which I’ve mentioned before. It will line up in history in its proper place one day among the Agricultural, Industrial, and Information Tech Revolutions. This is the Genetic or Medical revolution unfolding.
That’s absolutely fascinating Jo. I wish a human-based solution to ageing would happen in time for we old dears! Not meaning you, of course! 🙂
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Good gracious me! Did I manage the number 1 spot again? It was quite inadvertent
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Entering the cli-sci zone here, ain’t we? Still, better than
the cli-sci. https://www.youtube.com/watch?v=FxMyuF3hkSE
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Oops, sci-fi then cli-sci, silly serf. (
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I’m eagerly awaiting for the cure to cancer, not necessarily for myslef but for some close friends and relatives. It could be closer than most people think. Of course if they had spent on cancer research the money they had wasted on the CAGW scam we probably would have had a cure already.
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True.
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If anything we have spent more on the “War on Cancer” since Nixon coined that phrase. Estimates seem to be around the $500 billion range in the Us alone. Cancer is in most cases a disease of aging, so until we can turn the clock back on our cells, we will basically never cure it.
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Great post. Interesting research.
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Jo, what a fantastic change to read a truly scientific post rather than the more usual posts featuring some political aspect of climate change. I had it in mind to ask if this site would be returning to its scientific base and thus, to me,this story is so welcome.
From previous off site correspondence with you we were both working in similar fields and I wonder if you have posted anything on CRISPR. I haven’t seem anything here as I haven’t visited this site often in the last few years. As I’m quite sure you know, CRISPR is one of the latest developments in the manipulation of DNA. Have you come across any papers such as this one which tell a story that has general interest? Perhaps an article on mitochondria might be interesting to your readers for I wonder how many are aware they originated from the internalisation of bacteria by a pre-eukaryotic cell.
I would be most interested in your thoughts on “the treatment of the mice with the antibiotic doxycycline acts on an enzyme that causes depletion of mitochondrial DNA because the enzyme to replicate the DNA becomes inactive”. Is this inactivation caused by changes in the the structure of the replicating enzyme itself or to the gene(s) coding for the enzyme? What this enzyme is I didn’t see mentioned, However this comment on the action of doxycycline on cells is very informative. II is from a paper discussing, inter alia, the action of doxycycline on breast cancer stem cells that contain increased levels of mitochondrial proteins.(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580062/_
Particularly, one of the best doxycycline targets identified by our quantitative proteomics analysis was DNA-PK, the catalytic subunit of the DNA-dependent protein kinase, which is required for proper NHEJ (non-homologous end-joining) DNA repair [6], for maintenance of mitochondrial DNA integrity and copy number [7], and it confers resistance to radiation and chemotherapy in cancer cells [8]. Interestingly, DNA-PK was also found to be up-regulated in mammospheres, and its genetic knock-down or pharmacological inhibition using either doxycycline or an established DNA-PK inhibitor (NU7441) blocked that mammosphere formation. In fact, a closer look at the chemical structure reveals that doxycycline is a reduced carba-analogue of other DNA-PK inhibitors (Figures (Figures11 and and2),2), although the direct interaction between doxycycline and DNA-PK still needs to be proved.
Thanks for such an interesting and thought provoking post Jo
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Ian, CRISPR? No, not yet! Lord knows I have been tempted so many times. Yes, it’s long past time I started sharing some of my other interests. Yes, I’m already writing that general article on mitochondria because they are so magnetically fascinating.
Regarding Doxycycline, my shallow reading of it assumed that they had set this up as the artificial trigger — which seemed an odd choice that muddied the results because an antibiotic will have other confounding effects. You obviously know more than me. I’m interested in the action of rapamycin on kinases, but didn’t realize that this particular targeting may be intrinsic or specific to doxycycline. Ooh ooh ooh. Now I see that the molecule itself is very interesting (eg PMID on Tumor suppression). Thank you.
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Jo, very interesting stuff. (But I still like the posts where we get to kick Turnbull and Frydenberg. They’re so kickable. Plus we have a coal industry not just to save but to modernise and expand. No small thing.)
On the subject of ageing, tobacco lobbyists needed a play to use on the European Union. They actually paid a Czech consultant to come up with a convincing case. He produced evidence couched in academic gobbledeegook that smoking tends to kill productive people just around the time they start needing to take resources from the system. The EU, being friendly to scientific evidence and uber-rich lobbies, are open to these visionary approaches.
It does occur to me that research related to making older people healthier and more capable is worth the punt, even going way beyond the familiar basics of diet, exercise etc. The old aren’t going to go away, despite British Tobacco, the birthrate is not going back to Leave It To Beaver days any time soon. You work with what you’ve got, and we’ve got lots of old people. Need to watch out for the Frankenfaust aspects in the age of stunt-science and Publish-or-Perish, but can’t stand still on this either. Longevity on its own isn’t cutting it.
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No fear. I’m not letting up on putting the boot in.
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‘Perhaps an article on mitochondria might be interesting to your readers for I wonder how many are aware they originated from the internalisation of bacteria by a pre-eukaryotic cell.’
Ian,
Wonder if you’ve read this book? If not, thought you might find it of interest.
The Slow Death of the Aids/Cancer Paradigm
and the Apocrypha of the Eukaryotic Cell
by Nancy Turner Banks MD
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And meant to say that I thought you might find it of interest too Jo.
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No I haven’t Joseph, Thanks for drawing my attention to it
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Maybe they’ll find a cure for leftism Ian other than the usual collapse of society rebuilt by decent humans method.
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They might well but as you don’t define leftism nor define decent people it is a bit hard to guess. But if by leftism you mean those who can think on more than one level about more than one topic at one time they don’t need curing they’re already cured. And if by decent people you mean stuck in the mud Conservatives with shackled minds and who haven’t left the 1950s yet it’s far too late. They’re beyond saving.
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But isn’t ageing caused by global warming? Those mice sure look they’ve been carbonised,
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The direction the world and society is heading in this ‘Age Of Stupid’, if Scientists discovered how to stop or reverse aging altogether, I wouldn’t be the least bit interested. At age 68 with the body and health of the average 45 year old, I am nether the less ready to check out anytime the Grim Reaper comes a callin !
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The world drug companies would not allow the above research to take hold if it were successful. They make too many billions prescribing drugs and chemicals to those millions who suffer from various ailments caused by the march of years.
That is also why they hate naturopathy………..naturopathy, in simplistic terms, being the use of methods to stimulate and encourage the immune system to keep an individual physically young!
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Another interesting piece of aging research is on the molecule FOXO4-DRI. Its effect were completely systemic in mice, not merely skin.
However, I’m not going to be a “Mercy Man” with it yet. . . .
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I believe that that aging is such an intrinsic and fundamental part of human cell functioning that we will not live longer than the current limits, for the foreseeable future.
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Starfish can regrow an arm, some sharks live to be 400, Some trees 5,000. There is no law of physics that says a self repairing creature has to age.
Until we understand why we age we really have no idea what the limits are.
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Interesting to think what the ‘self’ is in us self repairing critters. Pretty much all of the cells that make up our body get renewed over the years and so our body is never the same person it was. What are we to preserve? The blueprint, the DNA? We can do that now and ‘live’ in an information archive somewhere (perhaps that great suppository TonyA spoke of). Or is the ‘self’ nothing more than a construct of the memories and experiences of the flesh? We as humans have evolved sophisticated methods to archive and pass on those memories and experiences to future generations.
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You state “I believe that that aging is such an intrinsic and fundamental part of human cell functioning that we will not live longer than the current limits,
.But history doesn’t tell us that as “current limits” keep changing. If you had written that comment 200 years ago life expectancy was much less than 100 tears ago and both were much less than today. But now, with the same set of cells life expectancy is so much higher. Will your comment still be validdin 2100? 3100? Probably nor but who knows?
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But the planet will be destroyed by the CO2 death spiral by then Ian, caused by dangerous ideologues like Jo who also want to better humanity….oh the bitter irony Ian!
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Very droll. Good to see you are still unabl to focus on anything but climate change. Do you like being so utterly one dimensional?
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Why are you so critical of others and so blindingly intolerant.
We do learn a lot from people like you, but it’s only useful in helping to see how far this social disaster has embedded itself in the world.
Looking deeply into the CAGW movement it is easy to pick out the usual drivers that are present in most wars and societal collapses: The push for Power, Money and Control by manipulation of a vulnerable part of the population.
Those doing the manipulation have absolutely no concern for those they use, as witness the infamous Nuremberg rallies and later deaths of many of those who participated.
Manipulators have no concern for the expendables.
Instead of moving forward to a decent, properly founded future, we here in Australia are destroying our Society and heading nowhere in a hurry.
It’s sadly all too obvious where you stand in all of this.
KK
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And even more sadly to see where you and many commenters here stand. I suspect none are climate scientists I certainly am not but i am not vain enough or stupid enough to dismiss the studies of climate change as being deliberately falsified by researchers all over the world to ensure they receive billions of dollars in grant money. Nor do I believe that all climate change is caused by humans or that all climate change is due to natural causes. Nor am I stupid enough or vain enough to claim as donon climate scientists such as yourself that my opinion is more valid, more significant and more accurate than the opinions of the many researchers in the field. Clearly you are both.
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Yes.
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Yes.
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Up at #6 we have: “Jo, what a fantastic change we have” and from past comments and “form” I would have expected the next bit to be, “with no discussion on the merits of coal fired power”.
Judging from several threads where comments have been made, there has been a permanent theme of anti Abbott, anti coal fired power generators and persistent misrepresentation of comments by others. One comment on the recent Canadian thread received 38 indications of disapproval.
In short, even in his own specialty, biology, he twists the facts to belittle the comments of others.
This makes all of his comments suspect.
The suspicion that this was all about disrupting the discussion on the failings of Renewables just won’t go away.
He does seem to know some biology but has no clue about the CO2 _ Climate Change scam and associated science.
All that is projected there suggests that the writer has been imbibing some of JonCookes Koolaid.
To more important stuff.
What makes a blog on the global warming scam so interesting is that involves so many facets of life.
For example, the science that CO2 is some sort of debil_gas is a preposterous lie.
The science is simple and I feel confident that Will Janoschka would support me on this.
The temperature at any point in the atmosphere is nominally independent of composition and primarily dependent on depth.
The suggestion that a change, even a doubling of CO2 in the atmosphere, would heat the atmosphere is scientific Rubbish.
The thing that makes a study of CAGW so interesting is to ask the question, “how did they con so many people, how do they get away with it”?
And the movement of billions of dollars all triggered by the most beneficial and essential ingredients of our lives, CO2.
It’s a worthy study to see how this gigantic misdirection and enslavement of whole countries has been achieved.
This scam is brilliant and certainly worth our continued attention. It truly is the modern religion.
Can we find a way to swing the public back to reality?
That’s our task.
KK
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Well said KK.
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I was taught – albeit many years ago – that among many functions our DNA “partially unwinds” allowing for the construction of transfer RNA which carries the blueprint for – among other things – the construction of amino acids and proteins essential to all the functions of cellular life and reproduction.
The DNA is “capped” at each end with Telomeres whose sole purpose appears to be protecting the genetic structure of DNA.
As we age the continual need to reference the instructions for chemical reactions damages the Telomeres and our DNA strands effectively shorten over time as Telomeres shorten.
Once a Telomere becomes ineffective the DNA begins to break down and cannot function as it should.
If we could prevent damage to the Telomeres cellular damage related to ageing would cease.
At least that is what I was taught as the current consensus hypothesis during my studies in human physiology at Queensland’s University of Technology many years ago.
Not sure whether this research changes this hypothesis.
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You have a one track mind that allows you very limited scope to discuss anything but your pet prejudices. You are no scientist just a ridiculously partisan know nothing who has rote learnt phrases like CO2 is good and coal is better and monotonously and unthinkingly repeats them at any and every opportunity. As you are unable to discuss anything outside your prejudice zone your comments are just infantile, worthless drivel. Did you read jo’s comment to me? Rather different from the venomous spite you continually churn out.to belittle those who do not share your antediluvian views You’re a sad loser KK whose idea of scientific discussion is to make much of minor spelling errors.
Now to yet another o your futile attempt to appear as a scientist
You state “The temperature at any point in the atmosphere is nominally independent of composition and primarily dependent on depth.”
Garbage as usual. For a start the atmosphere consists of various zones: troposphere, stratosphere, mesosphere, thermosphere and exosphere . According to your definition the temperature in the thermosphere which is between 600and 900 km above the earth’s surface should be cooler that= the troposphere which is about 7 to 20 km above the earth. But it isn’t. Its temperature is about 1500C Unsurprisingly, that clearly doesn’t conform with your statement (https://www.space.com/17683-earth-atmosphere.html)
And f there are any spelling errors that I haven’t corrected make sure you do as that will add so much to your scientific credibility which certainly need ]s all the help it can get
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🙂
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I think that was directed at me.
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Not at all GeeAye. If it appears that way it was due to the way the system for replies operates here and i unreservedly apologise I should have stared with KK but I did put in yet another of his maladroit and incorrect statements which I hope you will recognise as not being one of yours.
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I am not keen on your attitude towards KK Ian. Most people here are more polite than I perceive in your last post or two. You may have some things worth saying but your attitude to a long-standing valued contributor doesn’t make for taking your views seriously.
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I wrote in a comment to KK that I had a PhD which I do. He called me a liar. I said I ‘as a scientist” which I am, he said I wasn’t a scientist. Had KK not put his venomous vitriol in hs comments`i’d have had no cause to say anything but he did and I have. Additionally `i’m fairly sure I joined this site before KK.
[This needs resolving offline, which I will try to do tomorrow. Please, tone down on personal insults everyone. – Jo]
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Jo I do not want any actions of mine to cause you additional work and/or problems. I will refrain from personal comments in any reply I may make to KK’s or indeed anyone else’s posts. I agree it is unseemly end i unreservedly apologies to you and KK in particular and to anyone else I may have offended either advertently (is there such a word) or inadvertently.
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Thanks Ian.
Helps if we all remember to slice and dice the points and not the personalities…
Temptation is ever thus.
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To Ian @ #14:
Ian said:
How is it “garbage?” I didn’t see that he mentioned anything about the troposphere, stratosphere and all the other spheres. (And neither of you mentioned cycles and epicycles.) Neither did he say anything about temperatures, you did, alleging he did. No Ian. Your attack on KK seems to be wanting, and your apparent knowledge of physics seems to be less than his.
KK’s said:
He is right, where depth means: “ the gas column height/depth in the gravity well.” Which makes him correct. You, Ian forgot about gravity. Read the paper. I’ll know you’ve read it when you publish your apology
(link below:)
This paper will help you with your physics. Try the maths … it’s not all that hard.
The space.com article you linked to is partly garbage. Venus is not the victim of “ a runaway greenhouse effect as it and so many others allege. It does have an atmospheric pressure of 93 bar (or 95 atmospheres c. 1620 pounds/square inch or c. 110kg/sq.cm), with gravity c. 0.9g. Compress a gas and it heats. You should know such elementary physics as that. KK does.
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A minor clarification:
KK didn’t mention any temperatures specifically but did mention the source or origin of any temperature at any height within the atmosphere.
That rendered Ian’s attack to the same level he claimed for KK. Garbage.
KK = 1, Ian = 0
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In Gulliver’s Travels Swift’s “struldbrugs” are immortal, although they age physically losing their teeth and hair at ninety, they also lose their interest in life becoming “… peevish, covetous, morose, vain, talkative, but incapable of friendship, and dead to all natural affection, which never descended below their grandchildren …”.
Gulliver’s appetite for “… perpetuity of life was much abated. I grew heartily ashamed of the pleasing visions I had formed; and thought no tyrant could invent a death into which I would not run with pleasure, from such a life …”.
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Interesting.
I can relate to that.
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You write
He is right, where depth means: “ the gas column height/depth in the gravity well.” But did KK mean that or are you assuming that he did? I responded to what he wrote. As the temperature in the areas of theupper atmosphere are higher than those lower down due to the effects ozone, that clearly contradicts KK’s statement. Had he mentioned it I would not have made the comment I did.
And as for the article to which i referred I chose it specifically because of to whom it was being sent.
I looked at the paper to which you referred and was surprised to find I had looked at previously. I am not conceited enough to claim I fully understand it but will make a serious effort to do so. I certainly do not understand the mathematical calculations and will not try to do so.. I will also look for other papers dealing with GMAT
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You state “Yes. I can relate to that”
I really didn’t think you’ were 90 or perhaps even older Elderly yes but not 90. You really are doing very well to keep posting here. Congratulations and well done!
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Well, since Climate Change will ruin the world, nobody will want a long life!
As for drug companies not wanting such news to get out, I think you have it wrong- any company which had a rejuvenation treatment that worked would have us coming back for more!
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q. How many Polar Bears would it take to change a light bulb…?
A. None- so who cares if they do all drown!
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No, we don’t have the same genes as we did when we were young – that’s the point. They accumulate errors and shorten teleomeres, and as errors accumulate, we get cancer. Cancer is not one single mutation, buy a series of mutations that accumulate. We cannot stop mutations because they happen whenever cells replicate (errors) as well as when they are exposed to mutagens.
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We have the gene to lengthen telomeres.
We also have good error correction mechanisms and back up clearance programs when errors are detected.
The theory that aging is just a collection of errors is being challenged by new theories related to mitochondria.
Nuclear DNA can be transplanted from cancer cells into healthy cells with healthy mitochondria and the cancer doesn’t continue. But share the damaged mitochondria from a cancer cell with a healthy cell and it turns cancerous. There is something much more complicated going on than a simple accumulation of errors. (And I don’t know how many types of cancer this applies to).
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I’m reminded of the statement made by the slightly eccentric scientist in the movie Jurassic Park.
“You were so excited by the prospect that you could do it (make amazing scientific advances) that you never asked yourself if you should.”
With the world’s population exploding and billions of people either living miserable existences in abject poverty or starving, the last thing we need is to help people live longer! Especially when, after the age of 60 or so, most people are no longer contributors to the common good but simply a drain on dwindling available resources.
Looked at from that perspective all this will do (when taken to its logical extreme) is put more pressure on the people in the age group of 20 – 60 years, both in terms of work load and also to create the wealth to pay for the passengers who want to live indefinitely.
Nowhere on earth needs more people!
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