Oisin and its spinout OncoSenX completed antiaging trials using synolytics to extend the life of old mice by 20%. They will have human clinical trials starting in early 2020. They will apply it to people with solid tumors.
They use a lipid nanoparticle to deliver a DNA plasmid into sensescent (aka zombie) cells. The old cells are triggered to die and this boosts health and longevity.
At Ending Age-Related Diseases, John Lewis of Oisin Biotechnologies discussed senolytics, which are drugs that kill senescent cells. He explained the differences between healthy and senescent cells along with the senescence-associated secretory phenotype (SASP) responsible for systemic inflammation. He went into detail about senolytics and what his company looks for when creating them, including details about suicide genes and biomarkers of senescence. He also discussed issues with bringing these drugs to humans and suggested oncology as a possible method for bringing them to the clinic.
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You are thinking in math. This is biology. There are at least 9 different mechanisms that constitute aging. Each is sufficient to kill you, all running in parallel. If they don’t cure them in the order they would kill you, and in quick succession, then you are out of luck.
The mechanisms are not the same thing as the well known diseases of aging…though there are obviously connections.
One might buy you15 years but only if you are young. If you are already old, it may give you 3 years…because you have all these other forms of aging doing their thing. Hence the need for a quick succession of cures. It is also why we must use the anti-aging techniques we have even if they are not well proven in humans. You want the 15 and not the 3.
I could be wrong. Maybe every one we remove multiplies previous gains. But that is probably fantasy land. And even if that were true, we would likely be disfigured in ways we have never seen before.
Consider also that at different ages different things tend to kill us. We have had centuries to try to cure cancer, heart disease, diabetes, etc. If you are the first wave on the escape velocity trajectory you and your fellow travelers are going to be the first to encounter new diseases we have never seen before. It is going to be difficult to even figure out how the disease works in time not to mention cure.
And if that was not bad enough, the number of disease killing people explodes. https://www.cdc.gov/nchs/data/dvs/LCWK1_2015.pdf
If this treatment gives you 10 or 15 more healthy years then that will give you time for other advancements to give you even more time until hopefully escape velocity is finally reached.
Where’s the citation?
actually, look up elective surgery costs, such as plastic surgery, enlargement/reduction etc vs non elective surgery, you’ll find the prices for elective are still competitive while non elective such as a bypass or transplant costs are increasing faster than inflation, here’s a good article on the subject which goes into the reason why non elective is raising in cost. https://www.aei.org/carpe-diem/what-economic-lessons-about-medical-costs-can-we-learn-from-the-competitive-market-for-cosmetic-procedures/
Good, keep up the good (blood) work!
Recently I read about an alternative approach for mitochondial rejuvenation.
The mitochondria in a cell form large strands with physical linkages to each other, allowing them to share their proteins so that mutant mitochondria survive. But during meiosis in germ line cells these strands are broken up, isolating each mitochondrion. Any mitochondrion which can’t provide its own gene products dies, and the surviving healthy mitochondria proliferate to make up for the loss. This is how newborns always get a fresh set of mitochondria.
Apparently some researchers have tried inducing the same trick on non meiotic cells. It worked… for cells in a dish, anyway. No one has a therapy for adult humans, but the same principle should apply if it can be transiently induced in vivo.
My hunch is that some good juice is starting to flow around 2040,
so you don’t need to be overly pessimistic.
10,000 steps a day?
I like the long walks too. I used to manage 20,000 daily but it just took too long. I need to get used to using the treadmill while goofing off on my computer.
The 30% figure sounds depressing, but if you eat well, don’t smoke or drink, and go for frequent walks or other activity, you’re healthier than 70% of people in your cohort already. You can always get unlucky and die in a fire or get cancer tomorrow, but there’s a lot you can do to keep the odds weighted in your favor.
I’m hoping things go better than the projections though. There’s a lot of people I want to make it.
Yeah, I was reading this review of NAD+ boosters here (https://brain.forever-healthy.org/display/EN/NAD+Restoration+Therapy) which suggested that a round of senolytics should be taken before treatment with NR/NMN. NAD+ might aid with cellular energy but can also apparently make senescent cells more active.
I don’t think they specifically said you can’t take them at the same time but… when you’re on a senolytic, do you want anything that makes senescent cells healthier, really? You just want them to get out of the way and die.
You know, part of me really wants to see the value added they can come up with, part of me really doesn’t. If we leave it up to insurance or universal medical care, we just get the government welfare gruel version. A body which won’t kill you, sort of perpetually in its 50’s. Flabby, not athletic, restricted diet.
The free market would let you purchase a ferrari body… but it’ll have a ferrari cost. And you just know they’ll purposely make the ‘economy’ model have disappointing genitals so they can up sell you, even though the manufacturing cost won’t be any different.
“Evolution has already transferred some of the mitochondrial genome to the nucleus. The problem has been that this requires very low probability mutations, so proceeds very slowly, in nature, even though it’s selected for.”
I am aware that some things appear to have been moved, however I still think most of those that remain, remain because of the hazards. There is a reason there are so many mutations. Metabolic process have a lot of energy. You don’t want high voltage power lines going through your living room.
Why do insects still have genes in the mitochondria? They have had trillions of generations to move the genes. Fruit flies have 35 genes we have 37 genes.
The idea that all these genes are equally better in the nucleus is far from evident.
I think if we want to improve it we should evaluate the mitochondria in other species. Birds, bats, boehead whales, naked mole rats, elephants…hundreds of organisms. Evaluate them for efficiency, temperature range, resistance to damage, speed of division, waste emissions… Best would probably be an engineered version taking several genes from different species.
If we can get our body temperature down, we can extend life dramatically. That is mostly contingent on our enzymes related metabolism many of which are in the mitochondria.
Hey, if you’d been following the life extension field since the 1970’s, like I have, you’d realize that we turned a corner about a decade ago, and things are moving really fast now.
It’s just a darned shame that Alan Harrington didn’t live long enough to see it. It took decades, but we’re finally following his advice: “Spend the money, hire the scientists, and hunt down death like an outlaw.”
“I am not a fan of moving moving DNA to the nucleus. This is hazardous stuff. A lot of energetic reactions involved. I don’t think there is any way to transport mitochondria across the cellular membrane.”
Evolution has already transferred some of the mitochondrial genome to the nucleus. The problem has been that this requires very low probability mutations, so proceeds very slowly, in nature, even though it’s selected for.
And SENS have already demonstrated experimentally transfer of one or more of these genes, so it’s definitely feasible. The downside is that this isn’t really the sort of thing that’s easy to pull off as a treatment for an existing person; it’s more of a species upgrade for the next generation. Which I’m all for, of course, but I’m acutely interested in potential treatments that could help me, not just my descendants.
There’s been experimental success with mitochondrial transplants in vivo, too. It’s used as a kind of last ditch treatment for some kinds of heart and lung problems. So certainly feasible.
The missing piece is getting rid of the mutants.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879881/
Yes, they have a DNA ring which has the advantage of no telomere ends to get chopped off at each division, but is also more exposed to molecular insults.
I am not a fan of moving moving DNA to the nucleus. This is hazardous stuff. A lot of energetic reactions involved.
I don’t think there is any way to transport mitochondria across the cellular membrane. Maybe selectively destroy cells with no good mitochondria.
Positive mutations in mitochondria are profoundly unlikely. There are massive numbers of these things and everything that can happen probably has. That is seen by the very slow rate of change in human mitochondria over the generations. Mitochondria travels through the female line. You will have the same mitochondria as your mother and her mother. If she has lots of age spots then chances are you got that sub par mitochondria. I have noticed that many of the 110 year old people have less age spots, which suggests better mitochondria. I suspect mine is not very good. Probably need to do a bunch of that HIIT myself. Not the most pleasant of exercise 🙁
There is something that can accelerate Mitophagy (the recycling of mitochondria): Urolithin A. They don’t really sell it yet, but it is made in the body from something in pomegranates, walnuts and raspberries. But apparently not in everybody. Hopefully they can synthase this stuff and make it cheap and plentiful because HIIT hurts.
You don’t factor in the increase of computer speed and capability accelerating the research speed (AKA Kurzweil Law).
Any year of increased lifespan the current research buy me, allow faster research to be conducted.
If I get to rejuvenation escape velocity could be debatable, but the speed is increasing.
Moore Law, in the last 120 years computation speed increased around 10K times from 1900 to 1950, 100K times from 1950 to 1990, 100M times from 1990 today. Other 20 years mean, probably, another million times faster/cheaper computing.
https://preview.redd.it/m2gelocangt21.jpg?width=800&format=pjpg&auto=webp&s=0324cc30b4878aa903da3890a06d8e0bc878ba84
If it is cheap, you don’t need any health insurance to pay for it.
You can pay it with cash.
If everyone alive does it, the competition to deliver the service will be huge like the pressure to reduce the price (or increase the value added to service).
I wish I was that optimistic and I’m even a bit younger…
“That seems to mesh well with HIIT exercise being the most beneficial for mitochondria.”
The details of mitochondrial degeneration are a topic I’ve looked into extensively. It’s actually a case of Darwinian evolution within the cell: Mitochondria reproduce inside the cell, and even have their own genome.
Mutations that cause them to stop producing energy reduce the rate at which they can reproduce, (Because of having less energy to devote to that), but also reduce the rate at which they accumulate damage, which triggers their being taken out by cellular cleanup mechanisms.
So the precise details of how the mitochondria are being stressed has a lot to do with whether the mutants have a selective advantage or not.
SENS is pursuing a strategy of moving mitochondrial genes to the better protected nucleus, which is a good idea in general. But it seems likely to me that you can treat mitochondrial degeneration by less heroic means, by producing an environment where the functioning mitochondria have a selective advantage over the mutants, and then getting even one or two good mitochondria into a senescent cell. It should then revert to functional.
In theory anything that caused generalized damage to both healthy AND mutant mitochondria would remove the selective advantage of the mutants, and ironically be protective. Maybe HIIT does that?
I’ll check into the boron thing.
They found that the best indicator of if you were going to die in a few years was how many watts you can generate on a machine (can’t seem to find the study though). That seems to mesh well with HIIT exercise being the most beneficial for mitochondria. That said, my grandfather lived to 97 walking every day.
Are you taking a little bit of boron? It is supposed to help calcium go where it is supposed to go rather than to the joints and such. https://www.ncbi.nlm.nih.gov/pubmed/7889887
They sometimes put boron in calcium and magnesium supplements though you can buy it separately.
The one I wonder about the most is the optimal way to do telomere extension and senescent cell clearance…particularly if one should be done before the other. Logic would suggest that you want to clear out the senescent cells first as there could be a cancer risk with extending the telomeres of these zombie cells. By the way, “zombie” turns out to be even more apt than they knew. Turns out these cells eat their neighbors: https://www.nature.com/articles/d41586-019-03271-3?utm_source=join1440&utm_medium=email&utm_placement=itkst
However, logic is no substitute for science, so which should go first or if they should just be done at the same time is unclear. And it may differ depending on your age.
The most likely interaction between many of these approaches is that they will help each other rather than impeding one another or producing unwanted effects. The healthier you make one system the less the body have to devote to trying to mitigate that and has more resources to deal with other issues.
I’ve never smoked, I’m not terribly fond of cake, and SENS is my favorite charity. But arthritis is limiting my exercise these days. Mostly just long walks, if my ankles aren’t feeling too bad.
Good points, the industry is finding multiple mechanisms that contribute to aging. Each of them will require different treatments – what I haven’t seen a discussion of, is if anyone is beginning to look at the possible interactions between the treatments? Based on what I know of the history of pharmaceuticals, we should expect that there will be several serious side effects to combining the initial treatments in this area.
Hold on Brett! Don’t smoke or eat cake, and do some resistance training at the gym, and donate $10 per month to Leafscience.org or SENS, or if you do charity walks/runs etc every year make those orgs your chosen charities, or become a decamillionaire and donate large sums….
Epigenetic changes such as DNA methylation should be partly resolved by removing old cells (senolytics) and replacing them with new stem and stem-derived cells (cell therapies)…. I think. If necessary, the stem cells can be treated to reset methylation etc before implanting them. Epigenetic reset on the cellular level has been demonstrated IIRC.
Same with mitochondria, telomeres, and other intracellular issues. A robust cell replacement regimen coupled with extracellular junk clearance (including cross-links) may well be enough for the vast majority of aging mechanisms, if not all of them.
This is starting to sound promising. I turn 61 in a couple months, and just got my most recent bloodwork back, all good. So it’s starting to look like I’m actually going to be able to benefit from some of this research.
Assuming I can afford it, anyway.
Maybe. But this is just one form of aging. We discover that there are more forms of aging every couple years. Each of these must be addressed. And we still don’t know how many there are. At least 9, so far, I think. But I would guess it is at least 15. Some may only take 10-15 years of intense research to solve. Senolytics is probably one of those. Telomere extension is coming along very well, though it has been in the works for decades. Though other forms of aging may take decades to even discover. Mitochondria recycling will probably go well. Glucosepane removal will probably come along in 10 years. There are lots of crosslinks, I don’t think anyone has figured out how to fix. That leads to stiff tissue that is easily injured. Correcting DNA methylation, histone modifications and such? That is a real challenge, and it is looking more and more like this epigenetics stuff is a major player in aging that cannot be ignored.
On the positive side, quality of life should be greatly enhanced by synoletics, mitochondria recycling, NAD+ boosters and glucosepane removal..even if we only get 20-30% more lifespan. Getting the right targeted antioxidants may also give us an extra 5%. 108 healthy years does not sound terrible. Obviously, that is far from the target of most life extension folks who want “escape velocity”. And who knows, maybe all these other sources of aging are addressable. Though I suspect there will be a few that will give them headaches for several decades.
These are first steps to extending life indefinitely. Don’t like it? Death will be optional, so there is no need for you to like it, the choice is yours. Plus this treatment will be relatively cheap and paid for by medicare and other insurance. So it will be available to everyone.