If real, it would be a revolution in terms of longevity
Unfortunately the median lifespan of mice tends to be at most somewhere between 128 and 135 weeks. Since the treatment was at 124 weeks, a 25% increase in median remaining lifespan doesn’t translate to a large increase in median lifespan.
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I look forward to more information on this research that Altos is doing. If this type of news is coming out this quickly (since Altos started only a year or so ago), its a good sign the company won’t be like Calico and never bring products or services to market.
More on this news is in this thread: The Cure for Death Means Billionaires Will Live Forever—and Be Rich Forever - #57 by Neo
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Initially OP’s post was linking a tweet that stated this, it seems they’ve edited this and now it’s just an embedded video.
This result is also similar:
124 week male mice. Inducible OSK via AAV. 1 week on/1week off cycle. 109% increase in median remaining lifespan. This is despite lack of expression in brain. I wonder how ICV delivery in tandem might impact these results.
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Yes, I think that tweet might have been mixing up the Altos’s study with the older one by the other group that you linked to in your more recent tweet:
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Thanks, so this was a 25% increase in median lifespan from a single injection? That sounds much more promising. OSKM relative to OSK does seem much more toxic to liver and intestine from what I’ve read. It’ll be interesting to see the exact formulation and methodology used.
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It appears to be what he said, but what does “like Yamanaka” mean… and as discussed in the other thread, we probably should wait with drawing any conclusions on exactly how and what they achieved, until they at least present at a scientific meeting or come out with a pre-print.
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Rick Klausner’s part of that presentation was great and caused me to look into cell reprogramming. I found a really good article to help me understand the process.
The long and winding road of reprogramming-induced rejuvenation
Organismal aging is inherently connected to the aging of its constituent cells and systems. Reducing the biological age of the organism may be assisted by reducing the age of its cells - an approach exemplified by partial cell reprogramming through the expression of Yamanaka factors or exposure to chemical cocktails. It is crucial to protect cell type identity during partial reprogramming, as cells need to retain or rapidly regain their functions following the treatment. Another critical issue is the ability to quantify biological age as reprogrammed older cells acquire younger states. We discuss recent advances in reprogramming-induced rejuvenation and offer a critical review of this procedure and its relationship to the fundamental nature of aging. We further comparatively analyze partial reprogramming, full reprogramming and transdifferentiation approaches, assess safety concerns and emphasize the importance of distinguishing rejuvenation from dedifferentiation. Finally, we highlight translational opportunities that the reprogramming-induced rejuvenation approach offers.
Preventive treatments targeting aging present a considerable potential as an alternative approach to combating aging-related diseases. However, to control the aging process—by either slowing it down or reversing it—one must understand the fundamental mechanisms of aging. For example, it is now well appreciated that epigenetic information is progressively lost over the lifetime of an organism, disrupting cellular homeostasis. Epigenetic biomarkers of aging (aging clocks) can predict biological age through a variety of training approaches, even when based only on the variance of DNA methylation during aging. Interestingly, reacquisition of the lost epigenetic information may be observed during the natural rejuvenation process that occurs during early embryogenesis as well as during cell reprogramming. These strategies are in line with the notion of reprogramming-induced rejuvenation (RIR), a recent discovery wherein old cells can revert to a younger state upon transcription factor or chemical treatments. RIR is commonly accomplished through partial cell reprogramming, a method in which cells transiently undergo an induced pluripotent stem cell (iPSC) reprogramming. In this perspective, we discuss recent advances in this area, offer insights how they are related to the nature of aging and rejuvenation, and highlight potential advantages and drawbacks of this RIR and its translational potential.
Partial reprogramming holds significant therapeutic potential due to its capacity for cellular rejuvenation. There are two primary approaches that may help realize the therapeutic applications of this procedure. Organismal rejuvenation is the most challenging but also the most direct approach, due to its potential to reverse aging in a manner that is independent of the identity of the cells to which it is applied. Methods for reversing aging carry the potential to generate therapies that are more efficient and effective than those aiming merely to slow down the aging processes.
While the reversal of biological age as measured by epigenetic clocks suggests rejuvenation, these two terms should not be used interchangeably39. Rejuvenation can be defined as the reversal of cellular or organismal state to a state that would be found in a younger version of the organism, even though the trajectories of aging and rejuvenation may not necessarily be the same. Epigenetic, transcriptomic, and chromatin accessibility clocks may be capable of capturing certain aspects of these overall states. However, the most striking difference between epigenetic clock reversal and rejuvenation lies in their relation to causality. The first developed clocks show high correlation with age6,40, but their causal relationship with rejuvenation is yet to be determined, which is crucial for ascertaining their value as aging biomarkers for this type of treatment.
In recent years, clocks claiming to measure biological age based on phenotypic aging and future mortality, as opposed to chronological age, have emerged41,42. Yet, their full applicability to rejuvenation has not been firmly established. One reason is that many clocks capture all age-related changes, whereas only some of them represent the accumulation of deleterious changes characterizing the aging process.
In this regard, the identification of CpG sites causal to aging through a Mendelian randomization approach coupled with age-related changes in DNA methylation, and the subsequent use of these sites for the development of epigenetic clocks is a new promising approach43. This strategy permits the construction of epigenetic clocks that may better predict longevity or a shortened lifespan. Interestingly, it was shown that commonly used epigenetic clocks are not enriched for CpG sites causally related to aging. Importantly, CpG sites that have a causal relationship with aging could be used to examine potential therapies. For example, DamAge, a clock specifically trained to capture age-related damaging changes in the DNA methylome, showed reversal of biological age, whereas AdaptAge, a clock trained to capture age-related adaptive changes, does not show this effect upon full iPSC reprogramming43. Further studies in this area may result in the next generation causality-informed clocks that are tuned for testing longevity interventions.
Additionally, persistence of rejuvenation mediated by partial cell reprogramming is an aspect that necessitates further investigation. A transcriptional analysis of adipogenic cells, reprogrammed for three days and then followed for an additional ten days, suggests that broad gene programs continue to exhibit rejuvenation62. However, it is crucial to note that cellular identity states of these cells post-partial reprogramming are not identical to those of their parental cells. It is essential to investigate in detail whether these cells maintain their rejuvenated states after the reprogramming period, lose all rejuvenation signs upon reverting to their initial cellular state, or experience an accelerated loss of their youthful states compared to regular cells. Therefore, the longevity of rejuvenation effects mediated by partial reprogramming continues to be a relevant and unresolved question.
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Another interesting question about Altos Labs mouse rejuvenation experiment is - why the hard cap of 25% on life extension?
From the other thread:
https://www.rapamycin.news/t/the-cure-for-death-means-billionaires-will-live-forever-and-be-rich-forever/5011/62?u=ng0rge
And Rick Klausner himself says “Most people die of disease. But there is this phenomenon that people at the end of lives just sort of stop and we don’t understand that and how that relates to all the other things we’ve been talking about doing.”
So with the rejuvenated mice, all their cells and organs are doing great, then one day they just keel over? What does the autopsy say that they died from? Can organs just stop for no reason? Do the mitochondria stop producing ATP?
I’ve also wondered about dementia being one of the leading causes of death…just how does it kill you? Can’t you be brain-dead and still have all your other organs functioning, so still technically alive? I found this -
“‘Aspiration pneumonia’ is a type of pneumonia caused by food or drink going down the windpipe instead of the food pipe and is one of the most common causes of death in people with dementia.”
"However, the brain is responsible for more than just thought, memory and understanding. It also controls our bodily functions including breathing, blood circulation, and coughing.
As diseases like Alzheimer’s or vascular dementia progress, they damage more and more of the brain. This damage eventually affects areas of the brain that control the body, causing systems to go wrong and shut down, eventually leading to death."
But I assume that an autopsy would show a system failure outside of the brain.
Also, what if they if they took blood for an Epigenetic Clock test right at the moment of death? Would it show a rate of aging at zero?
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I’m assuming that the mice still die from various cancers even if most of their tissues have been rejuvinated.
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I think Rick said that they’ll have results at the end of the summer. It sounded as if the mice were all perfectly healthy, but then they just stop. I wonder whether organisms might have a built in ‘expiration’ date. That it doesn’t matter how healthy the body is, we’re programmed to have a specific amount of time.I know there’s been some talk of the hypothalamus being a potential universal clock. It’ll be really interesting to see what the result is. If there is a hard limit, it’s an exciting problem to work on.
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It could also be related to the thymus shrinking with age, in which case I would love to see a trial using Yamanaka factors + HGH + empagliflozin.
Or it’s an issue with the extracellular matrix which the treatment does not affect. This is one of the reasons why naked mole rats live much longer than regular old rats and basically never get cancer.
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yes it is really interesting. If the organs turn into the organs of a young mouse, which he says, he even says that old mouse skin becomes like young mouse skin and when you make an incision, it starts to heal the next day, then why do these mice die? I wonder if a single dose only extends life by 25%? Or are some tissues or organs less affected by these factors? This is a really interesting but very exciting development.
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HGH shortens lifespan, so I’m not sure that would be helpful. It’s possible that the EM could play a factor, maybe the mice hearts become so stiff, they simply stop beating. I do think immune aging has a huge effect. I seem to remember reading somewhere some centenarians have effectively exhausted their T cells. My feeling is that it might be programmed and all reprogramming is doing is resetting the cells to live out their maximum capacity. I’m sure there’s plenty of reasons why that isn’t the case. Fascinating stuff, and I can’t wait to hear what they find.
I think he’s talking about TRIIM and TRIIM X which directly address the T cell problem and immune aging. A complete examination of the mice when they die should give us some answers.
See this thread:
https://www.rapamycin.news/t/first-hint-that-body-s-biological-age-can-be-reversed/1021?u=ng0rge
And posts here:
https://www.rapamycin.news/t/rapamycin-vs-hgh-as-longevity-therapies/11674/33?u=ng0rge
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I think there are better thymus treatments on the horizon. They’re are at least three or four companies developing immune regeneration treatments. I think TRIIM is really interesting but I have a feeling it’s a bit of a blunt instrument. It does seem as if HGH shortens lifespan, so it may just be offering healthspan improvements in the people they’re testing it on, but I think it’s probably shortening lifespan. That’s probably not a bad thing if you stay healthier and then decline more quickly at the end. There was an interesting talk at the Dublin Longevity Conference on it on the effects of HGH. Worth a listen.
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In a sterile lab environment, HGH is probably detrimental for lifespan. But what about the outside world teeming with pathogens?