#13

You do a great deal actually.
Yeah, it’s recovery time that’s rough. When I go hiking with my son , I can keep up for a day or two, but then I need a break, but he doesn’t.
Recovery time, that’s the rub. Is it mitochondrial function, endothelial function, stem cells, cardiac ejection fraction? I don’t know.
I do know that since rapamycin it’s gotten better.

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#14

I am impressed you are doing max weights. My ego liked the results, but my joints and tendons complained at night to the point of interrupting sleep and difficulty doing small tasks like putting on sock and shoes. The Rapamycin has helped me with recovery and I am guessing that its blocking some of hyper inflammatory reaction. I am trying to move to yoga to improve my flexibility and balance, but yoga is not in my wheel house of strong skill sets. I can put on my shoes and socks now. The main reason for the questions was hoping to pull from you journey lessons for me. I go to an Orange Theory gym now and they will occasionally have bench mark timed days - such as your fasted mile on a treadmill or your fastest time at a 500m row. The competitive side of me loves this. Breaking my record and seeing progress is right up my alley. My concern is the down side of maximal effort as we age and not being a stepping stone to a better performance, rather a stressor that breaks the body down or even accelerates that aging process.

You are about 23 years ahead of me, so I appreciate your insights since I would hope to doing as well as you!

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#15

Mainly, I have had to back off aerobic exercises because my ankles are trash from years of playing tennis on hard courts and running on asphalt. I wasn’t genetically endowed with good ankles. If I had it to do over again I would skip hard court tennis as it seemed to bother me more than the running. At 81 I feel great until I attempt to do too much.
The thing about resistance training is I have never regressed. My hands seem to be a limiting factor now. I like to hang and stretch my spine but if I do it too much it causes pain in my finger joints and I develop “trigger finger” that takes days to go away. That is what happened to me last time I overdid the weights. One of the negative things about feeling great at an older age is attempting to do too much. Rapamycin makes me feel younger than I am.

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#16

As an inventor, creator of IP, and business owner, it’s obvious sci-hub is a pirate/thief, without debate. She lost judgment in the US, never showed up to defend herself, has never paid.

https://www.nature.com/articles/nature.2017.22196

Stealing copyrighted knowledge and sharing without consideration, is illegal.

Creating and publishing high quality manuscripts costs money, this needs to be covered. But why are they “gatekeepers” of this knowledge?

Having said that, these publishers are running a cartel, charging exorbitant access fees. There needs to be a new paradigm/model for sharing publicly funded research, as the current “status quo” is not working. Governments and other entities who provide public funding should step in and deem the research in public in interest. The knowledge created is far too important to limit universal access.

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#17

Hard court tennis is brutal on ankles/knees. As a daily 3-4km runner, I need to minimize wear and tear for the long haul. I specifically avoid hard surface running for the reasons you allude, and run indoor treadmill. If I happen to run outdoor hard surface, my lower limbs are quite stressed post run. I feel nothing on my treadmill. That’s not to say the pounding is not having an impact on my knees/cartilage, but I’m betting on the reward/risk equation re all cause mortality risk reduction.

#18

I have a funnel for my information…
I follow a wide variety of science news media, and whenever I see a new target or compound linked to longevity I enter it into Google Alerts so that I can easily follow the science around that topic as it progresses, and automatically get updates.

https://www.google.com/alerts

Here is a sample of the 100 plus terms I have in my Google Alerts listing:

Screen Shot 2022-06-26 at 10.55.15 AM
Screen Shot 2022-06-26 at 10.55.15 AM994×710 88.3 KB

Actually - I’ve copied my entire list from my Google Alerts, in case anyone is interested. Here (below) is the full list of topics / key words I get notified on anytime there is something new on the web published on any of these terms - all longevity related.

Please - if anyone has suggestions on other compounds, therapeutics that may be interesting to follow - please post them here. I’m always looking for new additions…

  • Lef1 factor
  • “Interventions Testing Program” (ITP)
  • 15-PGDH
  • 17‐α estradiol
  • 3-hydroxyanthranilic acid lifespan
  • 3,4-dimethoxychalcone
  • acarbose
  • Age-related macular degeneration
  • Alfatradiol
  • Alkahest
  • alpha-ketoglutarate (AKG)
  • AlphaCT1
  • altos labs
  • Amazentis
  • apigenin
  • Artemisia scoparia lifespan
  • Astaxanthin
  • Atentiv
  • autophagy
  • Canagliflozin
  • David Sabatini
  • Digoxin obesity
  • Dimethyl Fumarate lifespan
  • dr alan green rapamycin
  • epicatechin
  • Epirium
  • ergothioneine
  • executive function childhood stress
  • FGF skin aging
  • fibroblast growth factor aging
  • Flow Neuroscience
  • Gdf11
  • Gemfibrozil aging
  • GTP-3
  • Harold Katcher
  • Hevolution
  • Hevolution foundation
  • Hydrogen Sulfide lifespan
  • IMYu
  • Intra-Cellular Therapies
  • irisin exercise
  • ISRIB
  • John Overington MDC
  • Juvenescence
  • kat7 gene
  • Longevica
  • Longevity Science Foundation
  • Lumateperone
  • lymphoid enhancer-binding factor 1 (LEF1)
  • metolazone
  • montelukast aging
  • MOTS-c age
  • mTOR inhibitor
  • Mycophenolic Acid lifespan
  • MYSM1
  • n-methylglycine
  • navitor pharmaceuticals
  • NIA interventions testing program ITP
  • NIA ITP
  • nicotinamide mononucleotide
  • nicotinamide riboside
  • Nir Barzilai
  • nugenics
  • Oisín Biotech
  • PDLH rejuvant
  • Prkar2a
  • Rapalogs
  • Rapamycin
  • Rapamycin Acarbose lifespan
  • REVEL PHARMACEUTICALS
  • Rhodiola
  • sarcosine
  • Senisca
  • Senolytic
  • senomorphic
  • Sestrin
  • SGLT2
  • sirolimus
  • Sodium phenylbutyrate lifespan
  • Sodium phenylbutyrate sleep
  • spermidine
  • stem cell CNS
  • Sulindac lifespan
  • Tony Wyss-Coray
  • torin2
  • UNITY Biotechnology eye
  • UNR844 presbiopia
  • Urolithin A
  • VCAM1
  • vcam1 age
  • verteporfin anti-scar
  • verteporfin scarring
  • Yamanaka factors
  • YTHDF2
  • ZGN-1062

For the most interesting compounds (e.g. rapamycin, canaglilfozin, etc.)

I also set up alerts for new papers on the topic - in Pubmed and BioRxIV

https://www.biorxiv.org

Podcasts/Youtube:

I follow sporadically the podcasts we list here on our site to get inside perspectives on the research via interviews with the scientists doing the work:

When the new research / compound/therapeutic process is identified, the next step is Pubmed or contact the author to get the paper (Sci-hub was great until it stopped being updated a year or so ago).

As far as a rational process to grade the information - the key, rough guideline I use to rank the study is a well designed, controlled study (obviously in humans much more valuable than mice), number of people /subjects in trial, improvement (in lifespan/or other measure) significance, and source /academic group for the paper, and funding source for the paper (Industry-funded papers are obviously less reliable, more biased, and negative results hidden more, than in NIA/NIH funded studies). And really, in the past decade, the NIA ITP program with its three-way study on each compound is just head and shoulders above all the individual, un-replicated study results - so they have become the unquestioned leader in terms of studies on longevity compounds and are so much more valuable because of this.

For new compounds to try personally, the calculations get much more complex… and Rapamycin is a good example. Rapamycin had been on my radar since it first started showing results in drosophila back in the early 2000s, so I followed it as the mouse studies came out and also looked good. But, the perceived risk around it was too great until I saw the 2014 Mannick Paper where they tested rapalogs in healthy population and had good results. At that point, the risk was well quantified and as people started using it, the risk/reward profile changed to one I was comfortable with.

The side effect profile was pretty benign, and dosing was easily modified over time to adjust any potential side effects.

As a point of comparison - Testosterone supplementation is something that has been around for decades, but I’m aware of no significant lifespan benefits, in clinical studies in any mammals. I’m not aware of any academic groups that have done lifespan tests. So while it might provide some perceived healthspan benefits, as long as I am healthy, athletic and active, I prioritize the compounds with strong clinical evidence with lifespan AND healthspan benefits over anything with just healthspan benefits. I want to keep my stack as simple as possible, and I realize that “more” could very easily mean “less” in terms of adding different compounds or supplements or treatments.

Its interesting, but for drugs that are already FDA approved, the adoption seems like it will be relatively quick in terms of use by longevity enthusiasts… so we are seeing drugs with good clinical / FDA history and NIA ITP results (like acarbose and canagliflozin) moving quickly into use (admittedly by the fringe of society interested in significantly longer/healthier lifespans).

This is especially true as the drugs go generic and prices decrease dramatically - for example at $600/month Canagliflozin in the USA is probably more than most people want to pay, but when you can buy the same drug for $60/month from India - the adoption rate goes up quickly.

So - I see the Mannick paper of 2014 as a good model for FDA drugs that might boost longevity, but which have a perceived higher risk of concerning side effects. Once its proven reasonably well in healthy people, then adoption will start rising quickly.

mannick2014Everolimus.pdf (354.2 KB)

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What was your lightbulb moment w/ Rapamycin?
#19

Wow! This is so good and I will have to read it a few times to take it in small bites, but wow! So thoughtful and methodical. Thank you!

FDA approved drugs make it easier to use due to the off label use criteria.

Longevity is important to me, but I have decided that Health span holds higher value in my determination of my personal approach. Also, my 401k may not last long enough if I live too long:) . Testosterone had dramatic health span improvements for myself and many of my patients, but I do not recommend anyone start it if they do not have symptoms issues that it may help or continue treatment if they do not see a quality of life improvement to balance the risks.

1 Like
Long-term financial considerations of Longevity that affect healthspan
#20

Awesome! Thank you for taking care of this for the benefit of all of us.

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#21

Unfortunately, because of my age, treadmills at my local gyms were nonexistent in my prime.
One gym I belonged to was a Nautilus gym that had only Nautilus equipment which was quite the fad at the time. Another featured only Universal equipment. It was only after the 90’s that some of my local gyms had treadmills. Yes, save those knees and ankles, you will need them, even more, when you get old.

3 Likes
#22

Indeed. Perhaps as I get older, I might switch to step master/rowing machine to still get the cardio, but eliminate the impact. Although I am super motivated, currently on treadmilll, unless I press the stop button, I have no choice but to keep running vs slowing down with other machine types. Keeps me honest. So just like eating, if you keep your hand away from your mouth, you eat less.

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#23

This is a really good episode from Peter Attia that outlines his thinking on reading studies.

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#24

another good thing to be “up” on:

The p -value is a number between 0 and 1 that indicates how surprising a study’s results would be if there was actually no effect. The lower the value, the more reason you have to suspect the results are “real”, as long as the study and statistical analyses are well-designed.

There’s more to the p-value than the null hypothesis

In this article, we are focusing almost entirely on a single core assumption needed when calculating a p-value: that the intervention makes no difference. As we said in the text, a null hypothesis presumes that the intervention being studied has no effect. However, this isn’t the only assumption that needs to be made to compute a p-value — how the data behave, how the data were collected, and what choices were made in analyzing and presenting the data all play a role. And if any of these assumptions are wrong, the p-value can be misleading.

Methods Glossary Graphic P-values_01
Methods Glossary Graphic P-values_012487×1391 151 KB

5 Likes
#25

Consider adding

Nootropics
PT-141
BP-157
FMD - Fasting Mimicking Diet
CIMT

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#26

carotid intima-media thickness test ?

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#27

Yes sir! Non invasive and decent literature behind it.

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#28

There seems to be some disagreement on CIMT:

From Peter Attia’s recent AMA on Heart Disease:

How can CIMT (carotid intima media thickness) be helpful in understanding ASCVD?

  • CIMT is an ultrasound that’s done of the carotid arteries in the neck
  • Peter finds this to be a completely unhelpful test for a couple of reasons:
    • 1 – It is so user dependent in terms of the operator
    • The operator needs amazing technical skill to get a really good look at those carotid arteries
    • 2 – If you will want to see a change in this, you pretty much have to have the same person doing it again and again.
  • This might be that this is helpful if you have major, major carotid stenosis
    • Evenstill, Peter would still prefer to to a CTA in this situation
  • There are no guidelines that are based on a CIMT
  • People look to this test because it has no radiation, but the CAC has virtually no radiation

“I don’t see an advantage of CIMT over CAC ”— Peter Attia

  • Interpreting results of CIMT can be confusing
  • A negative CIMT doesn’t tell much; it’s easy to miss things here
  • Obviously if there is a lot disease in the carotid artery, the CIMT will show it

Peter prefers a CAC over a CIMT

#29

butylated hydroxytoluene (BHT), showed a whopping 30% life extension in a study from 1979. Very quiet since. Cheap as chips, if there is some new info on this, it would be great to catch it.
Glycine and NAC, will be interesting to follow.

1 Like
#30

Interesting:

and from here:

The Database of Ageing-related Drugs

https://genomics.senescence.info/drugs/drug_details.php?compound_name=Butylated%20hydroxytoluene

Will add it to my watch list.

I wonder if its the whole issue around people not publishing negative results… perhaps there was another lab that tried to duplicate this, couldn’t and gave up (and of course, this type of thing gets discussed at the academic conferences, but never makes it out to the public at large)…

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#31

Of course - the entire list of compounds being tested in the NIA ITP program (that have not yet had results published) are good prospective candidates for anti-aging drugs to watch:

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#32

safety-xray.pdf (161.8 KB)
n

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