#41

Yes, it’s possible, although it’s going to be even tougher to rejuvenate cells without dedifferentiating them. Anyways, that has only very indirect relevance to autophagy.

#42

To me there are two key aspects of rejuvenating cells. One is to get cells out of senescence. I think the driving cytokine here is IL-10 (because it is an NF kappa B inhibitor).

My own experimentation indicates that by increasing Acetyl-CoA levels in the nucleus cells can stop being senescent and start functioning.

The second thing is increasing mitochondrial efficiency (the ATP/O ratio). This drives probably a mixture of tricarboxylate metabolism which feeds into Acetyl-CoA via the enzyme ACLY, but also probably has an impact on translation of mRNA into protein as that is particularly energy entensive for larger proteins.

Neither of these things require dedifferentiation.

I am doing a mixture of things inclined to hit these two particular pathways. Both in a sense feed into acetylation of the histone (and stalling of RNA Pol II), but I think there is an ATP issue in that when the cell presses the accelerator button for protein creation the engine does not produce enough power.

In the world of animals you can see particularly the impact of acetylation where Eusocial Queens have massively more acetylation of their histones (and longer lives), hibernating animals, however, have reduced acetylation.

In a sense aging is a form of mild and increasing hibernation where the entity does not come out of hibernation.

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#43

If the operating system, i.e., the software is responsible for building the hardware, you analogy fails, totally and completely. You should connect the dots before you call out “ignorance.”

#44

No it does not fail. You’re missing the fact that there is often a huge difference between the processes required to fix things and the processes that were required to build them in the first place. In a lot of cases, the methods and tools you used to build something cannot be used to fix it. As an example, if you have a silica, ash and limestone mixture to create glass you can create a glass using a furnace and a mold to shape the molten mixture into the shape of a glass. If the glass breaks you cannot use the furnace and mold to fix it. You can only use the furnace and mold to create a glass from scratch. Biology is often similar in the sense that many things that the body can create during development, the body has no mechanisms to repair. One example is the lens of the eye.

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#45

Although a lot of that is true problems like Sarcopenia and Osteoporosis arise from the cells not functioning correctly. In the case of Sarcopenia certain proteins are no longer created and in the case of Osteoporosis the bone building cells (osteoblasts) are not created in sufficient number whilst those that destroy bone (osteoclasts) continue to be created.

If that gene expression problem is fixed it will fix a lot of things, but not everything. For example although it may reduce the rate at which genes are damaged it will not in itself fix genetic damage already done.

However, if one considers the animals and plants with particularly long lives (bowheaded whales, turtles) it is clear that basic carbon based life using DNA has quite a bit of potential for long health spans.

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#46

I totally agree with that

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#47

1000 is a tall order, but we’ve already got rapamycin and acarbose and a few more things comping out of ITP. These can probably add a decade or so to lifespan.

A genetically gifted person who was already going to live to 85 might now live to 100 in good health even with no additional discoveries.

But it seems crazy to believe that nothing will come of the literally billions being poured into epigenetic reprogramming over the next 40-50 years. Maybe that tacks on another 10-15 years. That’s quite a runway for new discoveries and developments.

I think we’re at the first time in history where something resembling longevity escape velocity is at least a plausible outcome.

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#48

I hope you are correct. I would love to reach longevity escape velocity.

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#49

Once you have a repeatable method of reversing effects of aging even slightly (rather than just slowing the effects), the math changes dramatically

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#50

Seems like the range of uncertainty around the answer this question is very large.

At the same time, it seems like we cannot reach the answer by analyzing current or historical speed and progress rates of science, technology and medicine.

Rather we need to base the analysis on things such as what the world’s capabilities for scientific and technological learning and progress will look like in 15 years, 3 decades and half a century.

Personally I think the evidence for scientific, technological and knowledge capabilities growing along exponential paths and along linear paths is quite strong. So the world’s technological and scientific progress during the decade from 2050-2060 might very well be an order of magnitude larger than all the process we have seen the last 50+ years from 1970-2023.

Btw - for someone who is less “hype focused” and has delivered quite massively scientifically to the world here is a perspective Prof George Church of Harvard and the Broad Institute yesterday

… quite amazing stuff

Helps one understand why he thinks that longevity escape velocity night not be that far off.

He was recently quoted as below

Professor George Church of Harvard Medical School echoes a similar timeframe.

According to Dr. Church, “The exponential technologies that have improved the speed and cost of reading, writing and editing of DNA and gene therapies, now apply to the category of aging reversal.”

He adds: “I think age-reversal advances could mean that we reach longevity escape velocity in a decade or two, within the range of the next one or two rounds of clinical trials.”

So, what does that mean?

Can we extend the healthy human lifespan past today’s record of 122? Can humans live past 200 years? Or even indefinitely?

Summary of talk - it’s quite short, so recommend watching it.

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#51

In this talk, Dr. George Church discusses the current advancements in affordable gene and cell therapies aimed at age-related diseases, including their potential for significantly improving health outcomes. It includes a discussion about advancements in genomic engineering, particularly focusing on the use of CRISPR technology to modify pig organs for human transplantation and developing resistance to various forms of damage.

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#52

If improving skin aging markers such as age spots, elasticity, thickness, etc., indicate age, then rapamycin in my experience does reverse aging somewhat. Younger people might not notice much but for older people the change is significant. I don’t know how much is attributable to taking it internally or how much to attribute to the rapamycin spray I am using. Rapamycin taken internally for a few months has had a very significant effect in reducing my actinic keratoses problem. I added the spray several months after starting rapamycin so I don’t know how much it has added to the removal of age spots, etc. That is because the change is slow. I hope rapamycin is having an effect on my internal organs as well.

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#53

I think Rapamycin operates through making mitochondria more efficient so genes are better expressed (particularly the longer ones). Hence with skin you would find things like skin oils being recreated, but that would not be something that would happen quickly.

The effects on autophagy from Rapamcyin would be happening over a few days after taking the drug, but the ongoing effects would last months and possibly years.

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#54

@desertshores, I finally made a spray last week inspired by your posts. Thank you

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#55

Do you use only rapamycin in your spray or are there other ingredients?

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#56

The spray I made has transcutol, methylene blue and distilled water.

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#57

Is there rapamycin in your spray at all? What do you use it for? Sorry for all these questions - I probably missed some parts of discussion.

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#58

@LaraPo, the spray I made has 5mg rapamycin (in a 2 ounce bottle), transcutol, distilled water and 500mcg of methylene blue. The methylene blue was my addition just because I found it helps my skin before I became interested in longevity so I’ve continued using it.

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#59

A few reasons to be optimistic here.

This field of inquiry has largely been ignored by science and was even a shameful idea to talk about. It’a very recently been considered a legitimate field and tons of money has poured into it.

There also appear to be many mechanisms involved in aging that are incredibly “simple” (mTor, epigenetic noise) and ancient and conserved. So we’re not talking about a super mysterious and complex human-only phenomenon like Alzheimer’s. This is something that goes all the way back to yeast. And there have already been big discoveries in a short amount of time (rapamycin, yamanaka factors).

It feels like the magical brief period of time between the discovery of bacteria and the discovery of penicillin.

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#60

Hi , New to the forum. How long have you been using this combination and with what results. I have developed a big sun spot on my forehead a couple of months back. Maybe Melasma : hope it helps
Regards
Rituparn

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