18 replies to this topic

[Florian Xavier]

I mean Aubrey de grey have litteraly increase his timespan.

 

Now it is 1/2 in 25 years if funding come with at least >10% in 100 years. It is worse.

[HighDesertWizard]

Without a reference link your post is close to impossible to understand and respond to.

Do you have a url you can post that documents the change in de Grey's position you suggest has taken place?

Assuming he hasn't changed his position on key questions that he expressed in his 2015 interview with with Rhonda Patrick, it makes sense to me that he would become more pessimistic.



In the last year, I've become more optimistic about achieving Longevity Escape Velocity personally by 2029.

:-)

[sthira]

In the last year, I've become more optimistic about achieving Longevity Escape Velocity personally by 2029.

:-)

It's refreshing to hear optimism and positivity in others (since my own brain seems to not allow much light in) about the future of regenerative medicine, so thank you. :-) But what about the last year has given you more optimism about achieving longevity escape velocity by 2029? Anything in particular, or just a general hunch?

[Florian Xavier]

Pretty much nothing happened last year

[HighDesertWizard]

Florian and sthira... I appreciate the opportunity to share my perspective... Thank you...

 

Feelings of optimism or pessimism within the Longevity Science Movement (LSM) can vary based on the objective one has in mind. I can't help but notice that you both take heart or despair from different Progress Markers than I do. If either of your Progress Markers ("regenerative medicine" and "recent good news from Aubrey") was my own, I'd be in despair too...

 

But my objective is different and my optimism about achieving it is greater today than it was a year ago. The last 18 months have seen tremendous advances related to my achieving it... achieving Longevity Escape Velocity personally by 2029.

 

Assumptions and Notes

• Accelerating to a LV of 1 (aka, LEV) will be easier from an LV value of 0.6, 0.7, or 0.8 than from an LV value of 0.2.
• I don't know that techniques summarized below are enough to get me to LEV but I believe they can get me close to LEV.

I'll summarize those advances below...

 

-----------------------------------------------------------
Reasons for optimism given my objective

 

Advances in Longevity Velocity measurement

• I presume familiarity with the concept of Longevity Escape Velocity (LEV). It suggests another concept: Longevity Velocity (LV), that might be greater than the Escape Velocity equal to one, or less, or more.

• It was always a mistake to think of the concept as applicable to large populations. Any step that makes it measurable in individual humans is a very significant advance.
  • If we can measure LV, then we can assess progress toward LEV in terms of specific, varied interventions in human studies.
• The last 18 months or so have seen profound advance in identifying key variables associated with aging. Age of a person from a blood sample can now be determined within some degree of confidence interval. Even more important, Remaining Lifespan is now being focused on instead of age.
  • Theoretically, this means that, over some period, LV is a statistical variable that may soon be calculable.
  • Take the estimated age from last year, calculated in some way from measures of Telomere Length and Epigenetic age, and do some relatively simple calculations to derive our LVs.
• Granted, there's a lot of work that still needs doing to make the above a reality. But I expect these sorts of services will be available in the next few years.
  • There are already multiple services that can be used to calculate Telomere Length and/or TeloYears age.
  • And there's now a service up-and-running(?) to measure Epigenetic Age too.

Aging has been Ameliorated via Manipulation of one of those Two Measures of LV noted above

• Epigenetic Reprogramming
  • In Vivo Amelioration of Age-Associated Hallmarks by Partial [epigenetic] Reprogramming
• And Aging Amelioration Effects on Telomere Length and Telomerase Expression via manipulation of the first
  • Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis
• Admittedly, it's early days, but...
  • now we Know a specific Age Amerlioration LEVER to try to manipulate
  • in our personal lives... Remember my goal is personal...
• Epigenetic and Telomere Length related variables are intra-cellular variables which raises a question.
• What is the mechanism for a relatively uniform aging process across the body

Removing Aging Factors from the Blood Circulation Triggers more Youthful Behavior and Appearance

• Various studies over years have demonstrated that aging factors circulate through the blood.
• A 2016 study, flawed in known ways, demonstrates some positive signs in humans

Evolution has established Mechanisms for Increasing Survival Probability Odds

• At least two Mechanisms established by Evolution have been shown to increase Survival Probability when triggered
• Both mechanisms inhibit NF-kB Cytokine Transcription.
  • This is important because NF-kB Inhibition has been shown to increase survival probability. I've been posting study survival curves about that fact here at Longecity.
• Heat Shock Protein
  • The 2015 Finnish Sauna Longevity study highlighted the benefit of HSPs for longevity.

 

 

• It's early days in the science of HSP-70 for increasing survival probability, but it inhibits inflammation in the blood circulation and that's all I need to get me excited.
• Sometime soon, I'll begin triggering the HSP inflammation inhibition mechanism with this device.

• Cholinergic Anti-Inflammatory Pathway (CAP)
  • CAP is the mechanism of action for a theory I call the Splenic Macrophage Inflammation Limitation Explanation (SMILE) of Longevity.
  • There is more evidence for the positive benefit of CAP than any other mechanism in any other Longevity Explanation.
    • If you disagree, let's discuss. I've posted lots of evidence. You'll need to have lots too to make the case against CAP...
• CAP is the mechanism underlying the positive survival probability benefit shown in the graphic figure below. A larger version of that pic is here. Study links for the survival curve pics can be found here at Longecity.

​

• I've spent 5 years researching and posting about CAP. Triggering it is the most significant LEV promoting tool in my toolbox. And I've got blood test results that demonstrate the benefit of triggering it.

• And if that weren't enough... How about this...

  • Kevin Tracey, the leading scientist of the CAP, gets funding by the US Gov DARPA Agency. Here he is, at a DARPA conference, describing research about CAP and thanking DARPA for the money...

 

And evidence now hints at the importance of inflammatory markers in driving epigenetic methylation

• I have my eye on IL-6 as the inflammatory marker most likely to be important in epigenetic methylation negative for health
  • Interleukin-6 Regulation of the Human DNA Methyltransferase (HDNMT) Gene in Human Erythroleukemia Cells
  • Over-expression of IL-6 and altered DNA methylation can regulate miRNA-370 expression in human cholangiocarcinoma
• PREDICTION: We're going to see an increasing number of studies showing that IL-6 is a causative element in triggering aging-related methylation.

-----------------------------------------------------------------------------------------
With that progress in view, I've recently changed my regimen...

 

At its core there are 4 new practices to address aging factors in the blood...

• Hit 'em high... by conscious and deliberate triggering of the Cholinergic Anti-Inflammatory Pathway. By reducing inflammation in the Spleen, the blood circulation system is less inflamed. (See Tracey Arthritis studies for evidence that this is true.)
• Hit 'em low... by establishing and maintaining a healthy gut microbiome
• Push 'em back with heat... by conscious and deliberate triggering of beneficial Heat Shock Proteins
• Drain the swamp... by making regular Red Cross blood donations (I've dumped 2.5 liters of old-age-factor rich plasma this year so far. How about you?)

 

:-)

Edited by HighDesertWizard, 09 July 2017 - 08:00 PM.

[Chris Pollyanna]

Personally I've become much more optimistic in the last 18 months, though bare in mind that I'm a fit and healthy 41 year old, so I have at least 20/30 years before I need to start seriously worrying! ;-)

 

A few highlights from the last year, starting with things you can do NOW:

 

• NR demonstrating small lifespan increase in mice and proof that it also raises NAD+ in humans
• Spermidine showing a decent increase in mouse lifespan even when initiated late & indications that humans with a diet rich in it have better health - eat your wheat germ!
• Synergistic effect between Rapamycin & Metformin shown in the ITP & a doctor (Dr Alan Green) has started prescribing them off-label 
• More good news from Valter Longo about the positive effects of the FMD
• Initial reports from some self-experimenters (here on longecity) on the positive effects of GDF11

Things coming soon:

• Senolytic drugs: Unity Biotech getting $116 million in round B funding - enough to get them into clinical trials
• The recent Foxo4dr paper - just look at the before and after photos of the mice in the supplementary material - wow!
• very recently in a pre-published paper showing for the first time ever a doubling of mean & max lifespan in c.elegans with a human approved 3 drug combo (rapamycin+rifampicin+allantoin), which was replicated in drosophila
• stem cells finally showing some efficacy re: Asterias trial in spinal cord injury

Further in the future:

• the Belmonte paper from December showing transient expression of the Yamanaka factors partially rejuvenated mice

 

And there was plenty of other things, but the above was just off the top of my head, so you can see that we are making good progress & the chances are getting better!

 

And if you don't believe me, just listen to the man Aubrey himself in his most recent interview:

 

[Florian Xavier]

I'm pessimist just precisely because of this.

 

All these papers in every science category for pretty much nothing. Just look at Tinnitus. Everything was promising, everything failed. This is how science is.

Edited by Florian Xavier, 17 July 2017 - 08:58 AM.

[Chris Pollyanna]

Hi Florian,

 

I'm curious as to why you are so pessimistic (apart from the fact that not all scientific discoveries pan out)? I must admit that I have no knowledge about Tinnitus research and any false promises that might have been made regarding it.

 

Also you say "All these papers in every science category for pretty much nothing" - what in your opinion would constitute as "something"?

 

In my own humble opinion, the list I provided above amounts to quite a few "somethings"!   

 

And to add fuel to the fire: the pace of progress in the last few years has reached a point where I have begun to dare to hope that my elderly but healthy parents (mid 70s) might make it to LEV with a bit of luck!

 

Chris

[Florian Xavier]

Just look at pain research, the substance P story for exemple. I mean it is too often like this. Things, in medecine, very often fail at some point.

 

 

[Chris Pollyanna]

That's a fair point, one just needs to look at how successful Amyloid Beta clearance has proven to be in Alzheimer's!

 

However, my optimism stems from the multiple avenues of enquiry that are directed against ageing, as evidenced by my previous post. Although some will no doubt turn out to be duds, hopefully several will pan out (and we do need several as ageing is a multifaceted process).

 

If you drill down, taking senolytics as an example: there are natural compounds such as Quercetin & Fisetin; pharmacological agents such as Dasatinib & Navitoclax; novel peptides like FOXO4-DR; and even gene therapy approaches as championed by Oisin Biotech. The eggs are certainly not all in one basket!

[Florian Xavier]

I think we need a bad news thread : http://www.longecity...g-than-thought/

[Nate-2004]

Pretty much nothing happened last year

 

Wrong: CRISPR

[Nate-2004]

Jeff Bezos just surpassed Bill Gates' $90 billion mark as the richest man. I don't see why SENS is not pursuing either one of these guys for just one cool billion, which could set us dramatically ahead of schedule.

[sthira]

CRISPR's been around a few decades; but you're right that knowledge appears to be solidifying around gene therapy as it finds speed.

About the billionaires, it confuses me, too, why not more involvement from them, what, they think their billions are useless against research into damage repair? Maybe they view it as the government's job.

Again, though, let's keep watching Calico Labs:

"Calico is a research and development company whose mission is to harness advanced technologies to increase our understanding of the biology that controls lifespan. We will use that knowledge to devise interventions that enable people to lead longer and healthier lives. Executing on this mission will require an unprecedented level of interdisciplinary effort and a long-term focus for which funding is already in place."

[Nate-2004]

CRISPR's been around a few decades;

 

What?! No way. Really? I don't think this is true. I'm pretty sure it was developed through 2015 and basically blew up as a news sensation in 2016.

[sthira]

CRISPR's been around a few decades;

What?! No way. Really? I don't think this is true. I'm pretty sure it was developed through 2015 and basically blew up as a news sensation in 2016.

Yeah, clustered DNA repeats have been around for a long time, named different names.

[APBT]

 

CRISPR's been around a few decades;

 

What?! No way. Really? I don't think this is true. I'm pretty sure it was developed through 2015 and basically blew up as a news sensation in 2016.

 

 

http://www.crisprupd...rispr-timeline/

 

https://www.broadins...crispr-timeline

 

http://www.nature.co...-s-life-1.19814

 

https://www.quora.co...invented-CRISPR

 

https://en.wikipedia.org/wiki/CRISPR

 

The first description of what would later be called CRISPR was from Osaka University researcher Yoshizumi Ishino and Aniket Walia in 1987, who accidentally cloned part of a CRISPR together with the iap gene, the target of interest. The organization of the repeats was unusual because repeated sequences are typically arranged consecutively along DNA. The function of the interrupted clustered repeats was not known at the time.^[18][19]

 

[Nate-2004]

Ok but I was talking about the culmination, the gene editing, not the years of related initial discoveries that lead to the use of CRISPR for gene editing. That became a thing in for humans in 2016, and I guess it really has developed for gene editing over the past 5 years according to that timeline. Still, I think my point was valid.  That gene editing with CRISPR has been around for decades is not true at all.

Edited by Nate-2004, 28 July 2017 - 04:21 AM.

[Nate-2004]

This stuff has only been showing up the past year and a half now: https://www.technolo...s-edited-in-us/

 

That's from the other day.