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!
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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)…
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:
@RapAdmin - I really need to get better at using your tools to be a better responder.
Dr. Attia is awesome and a source of so many valuable resources. His comments are the classic response we see from most traditional, but not all cardiologist.
In short, I think CIMT gives me and many others a tool that Calcium Scoring Test do not. Standard responses to his responses are the follow
A high percentage of pathology found in the carotid arteries can correlate with coronary after disease.
2.You need highly trained techs and cardiology/ vascular radiologist to read and follow - so find and use them
A Chest x-ray is about 0.1 msv vs. A Calcium Scoring CT is about 1.8 msv.
CIMT can see “soft plaque” not seen by Calcium Scoring and soft plaque are at more risk for rupture and stroke.
I start with CIMT and move to a calcium scoring test if needed - both triggered by an elevated risk and or abnormal advanced lipid testing - CRP, LpPla2, Lpa,
