Altos Labs Formed to Work on the Treatment of Aging

It remains to be seen as to whether Altos Labs is the new, large venture that patient advocates for the treatment of aging have been alluding to cryptically in recent months. It is apparently backed by a number of the high net worth individuals in the Left Coast business and philanthropy communities who are known to have a growing interest in the application of biotechnology to aging. Sadly, recent history suggests we should not expect much from such initiatives. Neither the Ellison Medical Foundation nor Calico Labs have done more than take on more of the same fundamental research into the progression of aging that is carried out at the NIA, at great expense, but no great gain. This is work that will not lead to rejuvenation therapies, and in many cases cannot even in principle achieve much in the matter of treating aging. The path to rejuvenation is to repair the known causes of aging and see what happens as a result. Unfortunately, most of the field spends most of its time trying to decipher how exactly aging proceeds in its complex later stages of cell and tissue dysfunction, without attempting to address those causes. Perhaps Altos Labs will be a different beast, given the apparent focus on cellular reprogramming. We can certainly hope so.

Last October, a large group of scientists made their way to Yuri Milner's super-mansion in the Los Altos Hills above Palo Alto. They were tested for covid-19 and wore masks as they assembled in theater on the property for a two-day scientific conference. Others joined by teleconference. The topic: how biotechnology might be used to make people younger. Milner previously started the glitzy black-tie Breakthrough Prizes, $3 million awards given each year to outstanding physicists, biologists, and mathematicians. But Milner's enthusiasm for science was taking a provocative and specific new direction. As the scientific sessions progressed, experts took the stage to describe radical attempts at "rejuvenating" animals.

That meeting has now led to the formation of an ambitious new anti-aging company called Altos Labs, according to people familiar with the plans. Altos hasn't made an official announcement yet, but it was incorporated in Delaware this year and a securities disclosure filed in California in June indicates the company has raised at least $270 million. Altos is pursuing biological reprogramming technology, a way to rejuvenate cells in the lab that some scientists think could be extended to revitalize entire animal bodies, ultimately prolonging human life. The new company, incorporated in the US and in the UK earlier this year, will establish several institutes in places including the Bay Area, San Diego, Cambridge, UK and Japan, and is recruiting a large cadre of university scientists with lavish salaries and the promise that they can pursue unfettered blue-sky research on how cells age and how to reverse that process.

Altos is certain to draw comparisons to Calico Labs, a longevity company announced in 2013 by Google co-founder, Larry Page. Calico also hired elite scientific figures and gave them generous budgets, although it's been questioned whether the Google spinout has made much progress. Calico has also started a lab whose focus is reprogramming; it published its first preprint on the topic this year.



So this is the big thing we heard all those months from Aubrey and others, about a seismic development in the anti-aging area, with big investments from famous rich people like Bezos. This is clearly not a new Calico, but not as promising as the SENS approach. They are still recruiting top scientists around the world, there is a possibility for SENS to get funded by those people or for Aubrey to start a new foundation with them if he can't get back his SRF. Still looks promising in my opinion.

Posted by: Jonathan Weaver at September 6th, 2021 8:20 AM

The one thing big pharma has gotten very bad at over the decades is developing new drugs

The "build it in-house bigger and better" model is over

That is why biotech exists in the first place

I don't understand the Calico model, or this Altos concept, for that matter

If you have the dollars that people like these folks do, why re-create the big pharma concept??

Spread it around to many researchers in lots of labs

That is where the real bio-magic happes

Posted by: David Petrov at September 6th, 2021 5:17 PM

Their intent is to develop a technology based on Yamanaka factors similar to

Posted by: Alex at September 7th, 2021 5:14 AM

Yamanaka will be part of the board , so they will use the factors for sure :)

Will they bring the best possible progress? Who knows...

Posted by: Cuberat at September 7th, 2021 9:04 AM

All in all I take this as a good development. Billionaires opening up their wallets is not a bad thing. Reprogramming cells in a lab is a lot different than doing it in a living human, so it's a tough moonshot to say the least. But it appears to be the moonshot they want to take. So good luck to them.

They also may make some progress with biomarkers, which is a very important aspect to understanding aging, and the impact of different treatments towards slowing it down.

I don't know what Aubrey De Grey's future is at the moment. It would be great if they brought him on board.

Posted by: Deleo at September 7th, 2021 3:03 PM

The good thing with anti-aging and rejuvenation is that it is not all or nothing deal. Unlike self-driving cars, even a tiny improvement is still useful. And once you have one single therapy working, then you attract interest and funds, so there will be even more therapies. The bigger question is whether we can speed or slow-down this process significantly. I am starting to think that at most by 10 years. A big change on a personal scale but nothing in the big scheme of things

Posted by: Cuberat at September 7th, 2021 4:11 PM

There is absolutley no point in re-programming cells unless that re-programming adresses the fact that the cells in question have a finite number of cell divisions (The Hayflick Limit) unless and untill that issue is addressed everything else is pointless.

Posted by: Christian Chase at September 7th, 2021 7:09 PM

Hi Christian! Just a 2 cents.

That is good point, there is conflictual information about that point; from one side they are saying the epigenetic clock is ticking independently from the mitotic (cell cycling) clock/telomere clock; yet, they show similarity and seem to be measuring/equating the same thing. In essence, they are morealike than we thought and do affect each other. Some studies they have no effect upon each other and thus are totally independent age readings. But, I think it is (now) actually, the inverse that is truer; they do behave independently; but they are Definitely connected. They used hTERT to disprove any connection between them (push back Leonard Hayflick limit/replicative senescence)...but it means nothing; really.

New studies have come and have looked deeper and realize that indeed, replicative senescence is a surrogate of epigenetic aging; it may be disconnected (like perhaps in some diseases that may show any specific telomeric attrition); but they saw that conformational/architecture (conformation) changes of the chromatin were Definitely correlated to replicative senescence - and - epigenetic changes/epidrifting. And it makes sense, epigenetic drifting is the loss of the 'earlier landscape' of epigenome; it changed to another landscape (peak and hills 'inverting' on epigenome - the more they invert the closer to death; that's because this inversion = gene activation/deleterious ones -> replicative senescence acceleration); plus, it was foud that telomeres (which are the replicative senescence 'counters') were working with epigenome and that they themselves affected it; that's because methylation (epigenome methylome) is part of telomeres (telomeres, sub-telomeres, centromeres, pericentromeres - all need methylation; they have TriMethylation (sub) to protect the structure of them; when telomeres shorten they 'change in conformation' (they are a part of chromatin changing), they can activate genes that proceed (hasten) to replicative senescence); Gene Silencing is crucial for pushing back replicative senescence - methylation is that element needed for that (methyls block 'genes/switches' to stay off); epigenome and its methylome lose global DNA methylation with age - not just there - in telomeres too. Thus, it is a manifestation of Both telomeres demethylation and epigenomic/methylomic demethylation;

there is 'CpGs' that hypermethylated or hypomethyated (the ones inflammatory causing and cancer higjacking), and with age its this pattern shift that causes havoc- it's not suppose to change like that...but that is the 'script/paper roll/scroll' of life (epiprogram), as the epigenomic land changes, so does the genetic makeup (what is activate and what isn't), this causes epimutation, chromatin mutation, disarray and just chromosomal havoc. The chromosomes will unpack, loosen, decondense and uncoil -> become loose -> replicative senescence. Chromosome need to be Tight, Compact, Coiled and 'Silenced/Methylated' -> Gene Silencing -> No deleterious genes -> push back sensecence.

There is correlation between the two. Telomeres are just the explanation in between. So all is not lost about the old 'Hayflick Limit''s after all, not an Entirely Totally Limit. It can be overcome and there is correlation between keeping enough methyl content and replicative senescence; we lose all the methyl residues in our life this will cause replicative senescence; people that age slower lose them slower and push back hayflick. When you have about 60-120 PDs (80 avg. population doublings) replicative senescence cell cycles; that's about how much the cells go as far (like human fibroblast) while for example, galapagos turtles replicative senescence is about 150-175 PDs; it's quite interesting to see it correlates to almost 1 PD per year (humans living 120 years and their fibroblast reaching 120 PDs...while turtles living 175 years and having cells that reach 175 PDs...thus, 1 PD per year); but that's the thing...population doublings and passages in culture of cells are time dependent and can become quite time independent -less so; in essence, a population doubling can be much quicker or slower (in terms hours, days... when cultured in vitro, in vivo is slower though), so it means, that it might be just 120 PDs...those same 120 ones...will always be 120 for humans...but what happens if those 120 take a 1000 years to happen...then it means Division of PDs Per Year...thus not 1 PD per year...1 PD per 50 effect multiplication and greatly Lenghtening or Shortening the Time to a PD. As in many more Cell Cycles are happenign much faster and the cell replicative much longer/proliferate faster..are not sluggish and 'senescent-like'...flat morphology, big and staining for B-Gal (Beta-Galactosidase, a marker for replicative senescence; same for p21; p21 is the ultimate marker/causer (it creates ROS excess tipping Redox towards unquenched milieu - ROS overtaking) of hayflick. when it comes, hayflick is soon; not p53 not p16...p21, (exactly) that one; p16 and p53 are senescence markers but for mostly 'Spontaenous senscence' thus, damage/oxidation that causes 'Premature Exit' from the cell cycle...not Replicative Senescence 'over time passage/cell cycles havinf reached their numbers/Rounds of replication # limit'); In humans' fibroblast it's about 80-100; and for centenarian they push it to 120 PDs..and yes they Live to 120 years too. (again, about 1 Pd/1 year),

I believe we will be able to overcome the hayflick replicative senescence Circumventing it...the body is capable of doing so; through the chromatin arrangement/rearrangements. That'S the scary territory of course, which epigenetic tinkering/reprogramming; it's scary to think that Full Reprogramming kills you (by 'erasing you/cell identity'), but Partial Reprogramming reverses your epiclock; the telomere and replicative hayflick limit may be able to be staved off; so long as telomeres are preserved (enough, I believe) because they are controllers of it and they

Themselves are methylated (when taller), but as they shorten they contribute to demethylation of themselves and the global epigenomic DNA demethylation. One study had showed that mouse and humans lose their content by a factor of 100; mouse losing them 100 times faster, humans 100 times slower; they live about 50 times longer than mouse. Sound about right. And it's not just Correlative - it is now, clearly (enough), Causative; epigenetic aging is causative of maximal lifespan and that is due to the DNA DSBs (DNA double strand breaks) that accumulate as DNA frags with age, from ROS excess and just the natural metabolistic process causing; the faster it is repaired the longer the animal lives, the faster accumulate the faster dies. IT was shown in an other rodent study comparing mouse vs naked mole rats/beavers, mouse (3 years), mole rats (30 years); they have Much higher SIR6 activity (which is histone related/chromatin related and forces the epigenome to 'Fix' the breaks/frags by calling DNA repair mechanisms (DNMTs, EXO1, XCCs, NHEJ, BER, NER, WRN helicase, Ku67) these elements protect DNA and repair DNA 'DSBs' rapidly; the faster they did that is why the mole rats lived 10 times longer than mouse (mouse hadvery weak DNA repair)...and this repair is Driven by the epigenome that will activate these DNA repair mechanism (SIR6, SIRs. FOXO, DAF and all these other ones). I would even say it fixes some of the Telomere foci and HSAF (Heterochromatin Senescence Associated Foci).

So, indeed, it all connects togethers/fits nicely like a glove. Ww just need to know how to fix them gloves and we will be 'glove and heels - ready for the show//pristine'. Or just like the ZZtop song goes: ''..Diamond rings, swede shoes, I ain't missing not a single thing....But when it comes down to it...Every girl crazy for the sharp-dressed man''.

Just a 2 cents.

PS: Sorry for the unashamed ZZtop plug there.

Posted by: CANanonymity at September 7th, 2021 11:22 PM

Each biological species is competing for its ecological niche. One all too often neglected area of research in rejuvenation is comparative genomics related to the lifespan of each species.

In particular for mammalians, what makes the naked mole rat so special, outliving 5x the usual mouse? I would like to see a complete genome map with keys genes different emphasized.

Same for the humpback whale relatively to other less favored whales or some kind of parrots etc.

On the other hand, why such marvelously intelligent animals like cuttlefishes and squids are so short lived? This is an untold biological tragedy, never will those species be able to transfer their exceptional learning abilities to their offspring as when they lay out their eggs, it's time for them to die, so sad...

This should be a staple for AI driven research now that the price of genome deciphering is plummeting. What are we waiting for?

Also, I profit to address the knowledgeable people here for another favorite of mine.
IMHO, the SENS mouse prize was preposterous as was all Mr. de Grey outlook at the problem of longevity (not surprising as he is "just" a former computer scientist turned lately up to a kind of geneticist).

He should instead, IMHO, have pushed for the Fly Prize, i.e. 100 Million dollars or even 1 Billion (if backed by donors) for the first laboratory showing off 1 year old flies (a 15x increased lifespan over normal longevity)! This would have pushed basic and applied research on more promising paths, if only...

Posted by: Paul Berger at October 4th, 2021 3:37 AM
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