In 2001, Aubrey de Grey and colleagues proposed ablation of senescent cells (ApoptoSENS) as the “damage-repair” strategy of choice for zombie cells. The idea was barely mentioned in the scientific literature. It was largely ignored until 2011 when a powerful proof-of-concept study showed that killing these “zombie cells” using a genetically-engineered “suicide switch” substantially rejuvenated a kind of mouse with a mutation that causes them to accumulate an abnormally high level of these cells.
The Mayo Clinic’s James Kirkland and colleagues developed an ingenious drug-discovery strategy that led to the identification of the first two of a new class of “senolytic” drugs. These drugs selectively destroy senescent cells. These zombie cells are barely able to block the “cellular suicide” mechanisms which normally kill them. Senolytic drugs tip the balance in favor of self-destruction.
In the three short years since that initial breakthrough, the progress in ApoptoSENS has been astonishing. Many studies have now shown that ablating senescent cells has sweeping rejuvenative effects. The rejuvenation is wider-ranging than SENS had predicted. Drugs and gene therapies that destroy senescent cells can restore exercise capacity, lung function, and formation of new blood and immune precursor cells of aging mice to nearly their youthful norms.
Senolytic drugs and gene therapies have
* ameliorated the side-effects of chemotherapy drugs in mice and
* prevented or treated mouse models of diseases of aging such as osteoarthritis, fibrotic lung disease, hair loss, primary cancer and its recurrence after chemotherapy, atherosclerosis and age-related diseases of the heart itself— as well as preventing Parkinson’s disease and (very recently) frontotemporal dementia, a kind of cognitive aging driven by intracellular aggregates of tau protein, which are also an important driver of Alzheimer’s dementia.
Normal cells can handle the inhibition of these pathways when not under stress, they still rely on them when damaged or when the local environment turns hostile. The tradeoff is worth it: that the benefits of purging the aging body of senescent cells far outweigh the dangers of a few lost healthy ones. This is true even in the brain (where killing senescent support cells protects neurons in mouse models of diseases of neurodegenerative aging like Parkinson’s disease and tau-driven dementias) and the heart (where heart function in aging mice is improved, likely by eliminating senescent cells left over from fibrotic responses to damage in the aging heart).
It would be better if there were a way of targeting these drugs more specifically to senescent cells, so that healthy cells wouldn’t be dragged through a trial by fire in order to ensure the elimination of their treacherous neighbors.
Best Senescent Cell Marker
The best and most universal sign of senescent cells is the activity of an enzyme called senescence-associated beta-galactosidase, or SA-beta-gal. All cells produce SA-beta-gal in their “cellular recycling centers” (lysosomes), but because senescent cells contain an abnormally high number of these organelles, they also produce very high levels of SA-beta-gal — so much so that its activity can be detected under conditions under which it can’t be detected in normal cells.
SA-beta-gal degrades the sugar galactose (one half of the milk sugar lactose), so scientists exploit the overproduction of the enzyme to detect senescent cells using chemically modified forms of lactose that change color when cleaved by the enzyme. But a few years ago, a group of scientists began to wonder if there was a way to take advantage of this property not just to detect senescent cells, but to selectively release drugs that would destroy them.
Researchers have used silica nanotubes (called mesoporous silica nanoparticles) to deliver anti-senescent cell materials. The nanotubes are closed off with material (GOS- galactooligosaccharide) which can be opened with the enzyme produced by the zombie cells.
If senolytic drugs were packaged up in GOS-MSN (galactooligosaccharide -mesoporous silica nanoparticles)? Existing senolytics expose all cells to their effects, depending on the different metabolic states of senescent and normal cells for their selective killing power. But the selectivity of GOS-MSN particles is different: they work by only releasing their payload of drugs in senescent cells, such that the great majority of normal cells are never exposed to the drugs at all.
And what if rejuvenation biotechnologists took advantage of the strengths of both of these approaches, by loading GOS-MSN ( galactooligosaccharide -mesoporous silica nanoparticles) with senolytic drugs instead of a generically toxic drug like doxorubicin? You’d expect that this would create a therapy “doubly-selective” for senescent cells: normal cells would almost never be exposed to the drug in the first place — and on the rare occasions when they were, most healthy cells would still escape unscathed, because of the drugs’ intrinsic selectivity for senescent cells.
Drs. Murguía, Martínez-Máñez, and Serrano have launched a biotech startup to turn GOS-MSN into a human rejuvenation biotechnology. Senolytic Therapeutics (Senolytx) projects that “Designed therapies will be efficacious in treating multiple disorders which are caused and driven by the accumulation of damaged cells.
ApoptoSENS type therapies could well be a significant milestone on the road to comprehensive human rejuvenation. ApoptoSENS therapies could treat certain many cancers, diabetes, arthritis, heart disease and more.
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
Known for identifying cutting edge technologies, he is currently a Co-Founder of a startup and fundraiser for high potential early-stage companies. He is the Head of Research for Allocations for deep technology investments and an Angel Investor at Space Angels.
A frequent speaker at corporations, he has been a TEDx speaker, a Singularity University speaker and guest at numerous interviews for radio and podcasts. He is open to public speaking and advising engagements.
Can these GOS-MSNparticles get past the blood-brain barrier?
So…. was the original comment about ‘horrible people’ removed?
Oh well, I can guess what it must have said.
If Fisetin is a senolytic I will be eating more strawberries, onions and cucumbers.
I take Now’s Quercetin 800Mg +Bromelain 165Mg daily. (also a total of +/- 20 other supplements). Hard to attribute general good health for a 74 year old without age spots to any one of them. What do you consider to be a high dose? I take Dr. Best Fisetin (as Novesetin) 100 Mg twice a day; said to remove senescent brain cells.
I take it periodically, one high dose a month. The first few times I noticed a couple of troubling age spots on my hands get inflamed, and afterwards the skin there was noticeably more normal. So I’m convinced it does work, at least to some extent.
There’s a gang in New Zealand that were up to no good in the 1980’s and 1990’s, doing gang stuff. Assaults, burglaries, robberies, etc. The gang members today are still together and now in their 50’s and 60’s. Do you know what they do now? They make sandwiches and take them to schools in poor neighborhoods. Maturity of individuals will ultimately mean the maturing of our society.
My understanding is that quercetin alone vs in combination with dasatinib is not as effective as Fisetin. Nevertheless I also take quercetin.
Future generations may marvel about how people in ancient times would have children and die while they themselves were still children and well before they ever had a chance to mature.
Seems to me that people who believe life extension is unnatural and can only lead to disaster should, as a minimum, stop going to doctors and dentists. In the neolithic, someone making it to 15 would have a decent chance of making it to 28. You think they would have objected to our current world average of over 70?
“terrible person” or (a little more selective) “demonstrably horrible people” – please define. Who decides & by what criteria? I’ll assume you’re not Stalin/Hitler/Mao, but you can see the problem – someone in power viewing all opposition as terrible.
Perhaps, no life-extension drugs for felons?
If you think there are billions of demonstrably horrible people, the problem is that your capacity to determine whether people are “demonstrably horrible” is completely shot. In fact, most people are quite nice.
While waiting for the drug, should the rest of us keep taking Fisetin; recently claimed to be a very effective senolytic drug?
“Let’s do nothing” is exactly the same as “Let’s murder everyone” – if you wait long enough.
Besides, bad people are rarely removed from society by death. When they are, it’s usually too late. We have better mechanisms in place to find and remove such people, which will still be just as applicable regardless of everyone’s longevity.
He doesn’t realize there’s any hole he’s in. Clueless misanthropy, or he’s only trolling, or both.
On the strength of your comment, I think you could improve humanity by getting rid of yourself.
It’s not like we’ll only give the treatment to the bad people. The good people will get it too, so the bad people won’t have any extra advantage compared to now.
And unlike now, people won’t be able to create massive problems and assume they’ll be dead by the time the bill comes due.
Yep. Living more, with more resources and energy will bring many parallel concomitant benefits: the desire to improve your world, because you will pass a long time in it, and this time meaning it, without self punishment and self effacement.
It will also engender the desire to make or see new worlds too. First in this Solar System, next beyond it.
The pieces are slowly moving for us to create an interplanetary society this century, one that will remove space and resource scarcity forever.
The last hideouts for scarcity and its follies will be in our minds and hearts, and even those will yield to our growing knowledge of how the human body and brain really work.
Even if it were true the argument fails because lack of scarcity of time makes it more likely people will move away to their own societies (just like people already do = countries) and live to see a world where you can move at least a whole solar system away. Without counting on what might turn out to make people even more timid for lethal danger.
And the predictability horizon of technology is getting closer which added to the above multiplies the shakiness of his/her argument.
“Billions of horrible people”.
You just don’t know when to stop digging do you?
Scarcity (of resources and now I would add, of time) is the enemy of humankind and the root of all evil.
It reduces humans to live in wretched animal misery, seeking to take advantage of others because of any minuscule advantage we can get. Scarcity makes humans behave as dogs fighting for a meager leftover.
Having a short time to live makes us evil too, making many of us seek to take advantage of others because there is only a limited time to live, so we better get the most of life by running over others or not giving a damn about the future.
If people were more certain they would live to see that future, they would be much more careful about what they do and to whom.
Removing resources, health and time scarcity from our lives would remove most of the sources of apparently unavoidable existential angst and strife on human life, with the rest of them becoming gradually ironed out by perfecting our technology or fixing our biological defects. Yes, even existential ennui can be fixed with the right chemical balance in your brain.
We simply can’t imagine it because we have never had that. So we say to ourselves that we should be resigned to suffer all kinds of diseases, die soon and that such is life, and never bother thinking what we could do if things were different.
But that is about to change.
You are effectively condemning billions to die unnecessarily, for the sake of an unproven assumption that there are billions of horrible people, which is as vague as unsubstantiated (“billions”).
The sooner people live longer the sooner the average wisdom of general population rises, and the sooner people see time the way they will see space once we’re out of this gravity well.
Are you serious or ?
Guns still work, you know.
And even today, a ‘terrible person’ can outlive you. Orneryness can be a longevity factor, too.
I don’t think you thinking far enough ahead. Most ,mental illness and antisocial behavior is caused by a imbalance in the brain, which will be easily fixable. Plus we will boost everyone’s IQ 5 fold.
Sneaky pun there. Good work.
Let’s kill everyone in case they turn out to be a horrible person.
That’s your argument? Really???
Is there any evidence that anyone in this conversation is a horrible person? Well… one person wants everyone else in the world to die. That’s a big warning sign if you ask me.
Sounds like a promising approach, which I’m eager to try myself.
Let’s move this research along faster! Our 10,000,000 years of previous generations have not been in vein.
Pretty cool stuff.
I take Now’s Quercetin 800Mg +Bromelain 165Mg daily. (also a total of +/- 20 other supplements). Hard to attribute general good health for a 74 year old without age spots to any one of them. What do you consider to be a high dose? I take Dr. Best Fisetin (as Novesetin) 100 Mg twice a day; said to remove senescent brain cells.
I take it periodically, one high dose a month. The first few times I noticed a couple of troubling age spots on my hands get inflamed, and afterwards the skin there was noticeably more normal. So I’m convinced it does work, at least to some extent.
There’s a gang in New Zealand that were up to no good in the 1980’s and 1990’s, doing gang stuff. Assaults, burglaries, robberies, etc. The gang members today are still together and now in their 50’s and 60’s. Do you know what they do now? They make sandwiches and take them to schools in poor neighborhoods. Maturity of individuals will ultimately mean the maturing of our society.
My understanding is that quercetin alone vs in combination with dasatinib is not as effective as Fisetin. Nevertheless I also take quercetin.
Future generations may marvel about how people in ancient times would have children and die while they themselves were still children and well before they ever had a chance to mature.
Seems to me that people who believe life extension is unnatural and can only lead to disaster should, as a minimum, stop going to doctors and dentists. In the neolithic, someone making it to 15 would have a decent chance of making it to 28. You think they would have objected to our current world average of over 70?
“terrible person” or (a little more selective) “demonstrably horrible people” – please define. Who decides & by what criteria? I’ll assume you’re not Stalin/Hitler/Mao, but you can see the problem – someone in power viewing all opposition as terrible.
Perhaps, no life-extension drugs for felons?
If you think there are billions of demonstrably horrible people, the problem is that your capacity to determine whether people are “demonstrably horrible” is completely shot. In fact, most people are quite nice.
While waiting for the drug, should the rest of us keep taking Fisetin; recently claimed to be a very effective senolytic drug?
“Let’s do nothing” is exactly the same as “Let’s murder everyone” – if you wait long enough.
Besides, bad people are rarely removed from society by death. When they are, it’s usually too late. We have better mechanisms in place to find and remove such people, which will still be just as applicable regardless of everyone’s longevity.
He doesn’t realize there’s any hole he’s in. Clueless misanthropy, or he’s only trolling, or both.
On the strength of your comment, I think you could improve humanity by getting rid of yourself.
It’s not like we’ll only give the treatment to the bad people. The good people will get it too, so the bad people won’t have any extra advantage compared to now.
And unlike now, people won’t be able to create massive problems and assume they’ll be dead by the time the bill comes due.
Yep. Living more, with more resources and energy will bring many parallel concomitant benefits: the desire to improve your world, because you will pass a long time in it, and this time meaning it, without self punishment and self effacement.
It will also engender the desire to make or see new worlds too. First in this Solar System, next beyond it.
The pieces are slowly moving for us to create an interplanetary society this century, one that will remove space and resource scarcity forever.
The last hideouts for scarcity and its follies will be in our minds and hearts, and even those will yield to our growing knowledge of how the human body and brain really work.
Even if it were true the argument fails because lack of scarcity of time makes it more likely people will move away to their own societies (just like people already do = countries) and live to see a world where you can move at least a whole solar system away. Without counting on what might turn out to make people even more timid for lethal danger.
And the predictability horizon of technology is getting closer which added to the above multiplies the shakiness of his/her argument.
“Billions of horrible people”.
You just don’t know when to stop digging do you?
Scarcity (of resources and now I would add, of time) is the enemy of humankind and the root of all evil.
It reduces humans to live in wretched animal misery, seeking to take advantage of others because of any minuscule advantage we can get. Scarcity makes humans behave as dogs fighting for a meager leftover.
Having a short time to live makes us evil too, making many of us seek to take advantage of others because there is only a limited time to live, so we better get the most of life by running over others or not giving a damn about the future.
If people were more certain they would live to see that future, they would be much more careful about what they do and to whom.
Removing resources, health and time scarcity from our lives would remove most of the sources of apparently unavoidable existential angst and strife on human life, with the rest of them becoming gradually ironed out by perfecting our technology or fixing our biological defects. Yes, even existential ennui can be fixed with the right chemical balance in your brain.
We simply can’t imagine it because we have never had that. So we say to ourselves that we should be resigned to suffer all kinds of diseases, die soon and that such is life, and never bother thinking what we could do if things were different.
But that is about to change.
You are effectively condemning billions to die unnecessarily, for the sake of an unproven assumption that there are billions of horrible people, which is as vague as unsubstantiated (“billions”).
The sooner people live longer the sooner the average wisdom of general population rises, and the sooner people see time the way they will see space once we’re out of this gravity well.
Are you serious or ?
Guns still work, you know.
And even today, a ‘terrible person’ can outlive you. Orneryness can be a longevity factor, too.
I don’t think you thinking far enough ahead. Most ,mental illness and antisocial behavior is caused by a imbalance in the brain, which will be easily fixable. Plus we will boost everyone’s IQ 5 fold.
Sneaky pun there. Good work.
Let’s kill everyone in case they turn out to be a horrible person.
That’s your argument? Really???
Is there any evidence that anyone in this conversation is a horrible person? Well… one person wants everyone else in the world to die. That’s a big warning sign if you ask me.
Sounds like a promising approach, which I’m eager to try myself.
Let’s move this research along faster! Our 10,000,000 years of previous generations have not been in vein.
Pretty cool stuff.