Useful Tests for Self-Experimentation in Rejuvenation Therapies, those Not Requiring the Assistance of a Physician
This is another in a series of posts in which I think out loud about how to organize and conduct a useful short self-experimentation or single person informal trial of an alleged rejuvenation therapy. The focus is on senolytic drug candidates, because those are the only potential rejuvenation therapies worthy of the name that are currently accessible to ordinary individuals such as you and I. The general points made here are applicable to any other novel therapy that might arise in the years ahead, however - and arise they will - as well as to assessment of personal fitness, should that topic interest you. You might look at the last post in the series for a general outline of how such a study would be planned at the high level.
The usual cautions apply in these matters. There is risk in using senolytic drug candidates: they are chemotherapeutics, and one should well understand their profile of side-effects and hazards - which means, at a minimum, reading through a fair few scientific papers and reports. Further, just about everything to do with taking matters into your own hands with any sort of pharmaceutical is illegal in the US, even those that are not controlled substances, albeit rarely prosecuted when it is a matter of individual use. "Rarely" is not "never," however, and the prevailing cultural zeitgeist is that you are a terrible human being for even trying this, regardless of circumstance. This is a sad state of affairs, especially for those who are dying, priced out of the US market but not the global market for specific pharmaceuticals, and nonetheless forbidden to make the attempt to help themselves.
Here, however, I will say little about senolytics, and instead offer a first take on a practical list of tests that might be used to assess whether or not anything happened as a result of self-experimentation in rejuvenation treatments. This is the essence of the thing: there is no point in trying a treatment and merely hoping for the best. That adds no value, and helps no-one. A world in which hundreds or thousands of people are trying an approach and publishing their own measurements is a different story, however. Should it come to pass, that will go along way towards helping to push more formal trials into progress, by identifying promising directions that might otherwise take some time to be discovered by the slow and formal trial process.
A Short List of Simple Tests
For a first venture, it helps to keep things simple and flexible. The objective is a set of tests that anyone can run without the need to involve a physician, as that always adds significant time and expense. Since we are really only interested in the identification of large and reliable effects as the result of an intervention, we can plausibly expect a collection of cheaper and easier measures known to correlate with age to be useful in this matter. Once that hill has been climbed, then decide whether or not to go further. Don't bite off more than is easy to chew for a first outing. I picked the following:
- A standard blood test, with inflammatory markers.
- Resting heart rate and blood pressure.
- Heart rate variability.
- Pulse wave velocity.
- Biological age assessment via DNA methylation patterns.
The cardiovascular health measures in that list are those that are impacted by changes in the elasticity or functional capacity of blood vessels, such as would be expected to occur to some degree following any rejuvenation therapy that addresses senescent cells, chronic inflammation, or other factors that stiffen blood vessels, such as calcification or cross-linking. Positive change of the average values in most of these metrics are achievable with significant time and effort spent in physical training, so movement in the numbers in a short period of time as the result of a treatment should be an interesting data point.
Bloodwork
There are online services such as WellnessFX where one can order up a blood test and then head off the next day to have it carried out by one of the widely available clinical service companies. Of the set of test packages offered by WellnessFX, the Advanced Heart Health is probably the most useful for present purposes. But shop around; this isn't the only provider.
Resting Heart Rate and Blood Pressure
A simple but reliable tool such as the Omron 10 is all you need to measure heart rate and blood pressure. It is worth noting here a couple of general principles for cardiovascular measures. Firstly, the further away from the center of the body that the measurement is taken, the less reliable it is - the more influenced by any number of circumstances, such as position, mood, stress, time of day, and so forth. Fingertip devices are convenient, but nowhere near as useful as something like the Omron 10 that uses pressure on the upper arm. Secondly, all of the above-mentioned line items also influence every cardiovascular measure, so when you are creating a baseline or measuring changes against that baseline, carry out each measure in the same position, at the same time of day, and make multiple measurements over a week and take the average.
Heart Rate Variability
There are surprisingly few consumer tools for measuring heart rate variability. Some of the regulated medical devices are quite easy to manage, but good luck in navigating the system to obtain one. The easiest way is to buy second hand medical devices via one of the major marketplaces open to resellers, but that requires a fair-sized investment in time and effort - which comes back to the rule about keeping things simple at the outset. After some reading around the subject, I settled on the combination of the Polar H10 device coupled with the SelfLoops HRV Android application. I also gave EliteHRV a try, but despite all the recommendations, I could not convince it to produce sensible numbers for the heart rate variability data, while SelfLoops HRV had no issues.
Pulse Wave Velocity
For pulse wave velocity, the situation for consumer tools is even more sparse. I was reduced to a fingertip device, the iHeart, picked as being less unreliable and easier to use than the line of scales that measure pulse wave velocity. The recommendations suggest that decently reliable data from non-invasive devices is only going to be obtained by measures at the aorta and other core locations, or with more complicated regulated medical devices that use cuffs and sensors at several places on the body. My experience with a fingertip pulse wave velocity measure is that it is possible to obtain consistent measures at any given point in time, but there is a large variation from day to day even when striving to keep as many of the variables as consistent as possible: position, finger used for a fingertip device, time of day, time since last meal and exercise, and so forth.
DNA Methylation
DNA methylation tests can be ordered from either Osiris Green or Epimorphy / Zymo Research. I picked Zymo's product because at the time I first wrote this, the Osiris Green founders were still bailing out their laboratory after Hurricane Irma; they are back in business now, however. I am told that these tests are very consistent over time, with the Zymo test claiming a range of error of two years or so for the age assessment when comparing two tests on the sample sample. Nonetheless, as for the cardiovascular measures, it is wise to try to make everything as similar as possible when taking the test before and after a treatment: time of day, recency of eating or exercise, recent diet, and so forth.
Scheduling
The schedule for a single person self-experimentation trial might look something as follows:
- Day 1-7: Once or twice a day, take measures for blood pressure, pulse wave velocity, and heart rate variability.
- Day 7: Bloodwork and DNA methylation test.
- Day 8 and on: Carry out the treatment.
- Day 30-36: Repeat the blood pressure, pulse wave velocity, and heart rate variability measures.
- Day 36: Repeat the bloodwork and DNA methylation test.
One person's data is an anecdote. We won't really understand the profiles of potential rejuvenation therapies, or indeed any new interventions, until a great many people have tried them and reported on the results of trying them. At the moment, that proceeds through small trials organized by a variety of companies. History suggests that few people will in fact self-experiment in a useful way that that adds to the bigger picture, but nonetheless, formal trials don't have to be the only effort taking place.
Costs of Measurement
For the choices mentioned above, the rough costs are as follows:
- 2 MyDNAge tests: $600
- 2 Advanced Heart Health tests from WellnessFX: $760
- Omron 10 device: $70
- iHeart device and Android application: $210
- Polar H10 and SelfLoops HRV Android application: $110
Which amounts to $1750, along with a fair amount of time spent reading around the subject and becoming familiar with the devices and their quirks. The hardware is of course reusable for any other health assessment you might want to carry out. There is a lot of reading material out there produced by members of the quantified self movement, for example, that focuses on assessing the results of more mundane matters of exercise, weight, and fitness. I encourage you to explore it.
For bloodwork, see: https://www.crsociety.org/topic/11880-blood-biomarkers-and-direct-to-consumer-test-vendors/
Note that it was written less for before vs. after testing of an aging intervention as for monitoring values over the long term as one ages, but there is obviously a high overlap and it should be useful for shopping around.
For HRV, the Quantified Self forums are filled with discussion, as are many health-related podcasts. Besides chest straps like the Polar H10 one can also get HRV from ballistocardiography devices (like the Emfit QS) that lay under one's mattress. The HRV measurement is automatic and doesn't require putting the strap on/off and laying/sitting still for a couple min each day. Supposedly the expensive Whoop Strap will do it via wrist optical HR sensors too. But the problem with HRV is that it is highly variable based on other transient things: overtraining, temporary illness, temperature, work or life stress. It's not clear whether averaging or using min or max values is the best way to smooth out these variations when using multiple readings over time.
Have the experts yet settled on a panel of biomarkers (and related tests) which will prove rejuvenation? At least for any animal at all?
Also, who is keeping track of which animals have been successfully made younger and healthier? And does anyone know if they've been reproduced by other labs?
What I'm interested in I guess is a roadmap of sorts.
thanks!
Euge
Es muy positivo que alguién como uds. aconsejen como acelerar el tema de las pruebas senoliticas, dada la burocracia existente en los temas medicos. Pero propongo hagan un criterio de selección menos ambiguo y asegurandose de que sea actualizado en cuanto a drogas y dósis. No hay que descartar una prueba rentada (que pague el interesado en hacerlo) por parte de alguna firma dedicada al tema de los farmacos senescentes. Saludos.
In English: It is very positive that someone like you advise about how to accelerate the issue of semantic tests, given the existing bureaucracy in medical issues. But I would propose to make a less ambiguous selection criteria and making sure it is updated in terms of drugs and doses. It is not necessary to discard a rented test (paid by the interested party in doing so) by a firm dedicated to the topic of senescent drugs. Greetings.
Very interesting. Osiris Green uses siliva, while Epimorphy / Zymo Research uses urine or blood. I wonder if the difference matters. I also wonder whether Epimorphy / Zymo Research is measuring pure or impure epigenetic age (as described in Steve Horvath's papers). Impure epigenetic age is a measure of immunosenescene and can be influenced by lifestyle, whereas pure epigenetic age controls for blood cell counts and therefore measures the mysterious, intrinsic aging process across all cell types. We need to find out.
Hi does anyone experimenting with this trial, I am not able to find doses and timing for the drug.
@salman: That will be the subject of a future post, for a couple of the senolytic compounds discovered in the past few years.
@NY2LA pretty sures it's the intrinsic, or as you call it, pure version Zymo uses. The only things shown to affect it are calorie restriction and rapamycin, so might be wasting your money using this as a delta. Whatever Horvath is measuring, it's not related to cellular senescence.
Perhaps these measuring systems (or equivalent) could also serve as methods to track the aging process (or reversing it)?
BodySpec DXA scan
https://www.bodyspec.com/
3D body scanner and reporting engine
https://www.fit3d.com/
Mark et al. FYI:
Epigenetic clock analysis of diet, exercise, education, and lifestyle factors.
Horvath S. et al
https://www.ncbi.nlm.nih.gov/pubmed/28198702
http://www.aging-us.com/article/101168/text
Full text is free. The different measurements here are expressed as extrinsic epigenetic age acceleration (EEAA) and intrinsic epigenetic age acceleration (IEAA). I for one would love to know why "poultry intake was negatively associated with IEAA".
Be sure to check out Figure 4.
Hi NY2LA ! Great study thanks for the links ! Just a 2 cent,
I believe why poultry would somehow be beneficial to IEAA is down to certain proteins and as they said, themselves, leanness of meat. Lean meat combined with vegetable allow a longer lifespan because these two - aviary and plant proteins amino acids are the most stable, while bovine and other types source of protein amino acids are oftenly unstable/contributing to mutation burden or excessive methionine intake (which makes for rising homocysteine which contributes to accelerated Redox loss by oxidizing the disulfide/thiols pools). Certain proteins aminos such as methionine have far reaching effects - they affect the DNA methyl clock: IEAA and EEAA. DNAMs (DNA methyl transferase) control IEAA, especially, and EEAA, partially; and are affected by that (such as cysteine, methionine, sulfur thiol, homocysteine and other of the redox). Thus, the protein composition is likely one answer to the chicken (and egg) riddle. Also, aviary proteins and other molecules of this origin are 'leaner' 'cleaner' flesh if you will with lower oxidative burden - mammals have a higher oxidative cell burden than aviary cells (this was shown in albatros like birds who have Telomer Elongation As They age and also pigeons whom live 35 years and have much lower oxidative stress than mice cells (again many studies show that) along with improved redox status - pigeon heart myocytes have better antioxidant protection/longer (thus better redox) and also, birds, in general, have higher amounts of bilirubin and other biles that protect against oxidative stress))) And, also, parrots live for over a Century - Centenarian parrots are not something out of the ordinary.
Parrot studies showed again the same thing, better blood TAC/FRAP/ORAC etc, basically they are emulating Our Centenarians (the human ones))...another one - the Andes Condor, lives up to 90 years old, big eagles live long - aviary protection by inherintely better 'cells' right from the start. It is a necessity for winged 'flight' (muscle function and powerful heart for blood circulation to wings)). Sure, chickens don't fly (yet neither pigs nor cows), but the gist is there; chickens are part of the bird fauna (distantly, they are more related to the ostrich and turkey genus of large 'non-flying terrestrial birds' whom happen to be ancient dinosaurs (chicken are 'small' dinosaurs; velociraptors were feathered lizards and resembled chickens it is a processus over 150 million years of evolution. Dinos -> birds 'remnants' of dinos).
One more thing, Retinoic acid (RA) birds have vert special RA pathways that allow them to 'form wings' unlike humans. RA pathway is capable of skeletal remodelling or litteraly 'Deforming' during infancy. RA has been shown to protect the body and is a powerful antioxidative; sometimes used in the eyes to protect the iris. Oftently, you see RA sold in skin products to remove skin pimples in kids. Aviary RA is rich and very strong, poultry contains that. More of that means more RA intake. There's more pathways that can explain, in part, why would Chicken - of all things - be helpful in any way.
And trust me, I eat Tons of EGGS - it nearly killed me (cholesterol filled eggs (400 mg cholesterol per european italian grass-fed chicken egg) - I had to stop that as it contributed to my atherosclerosis Dramatically. LDL is increased by that, I heard people say I ate a TON of eggs my cholesterol is in check, it happens for certain people - not for all. People whome have excessive immune activation (like me) and have deficient HDL production (like me again) are porducing way too much LDL species instead of HDL species and end up with atherosclerosis - despite eating HDL cholesterol in these eggs. The TOTAL cholesterol ends up rising and the HDL:LDL ratio skews towards MORE LDL/vLDL/LDLox than HDL and htat is fatal.
So this study you must take it with a grain of salt (not more because salt kills you, sodium hypertension (pun))).
Just a 2 cent.
PS: they do say that smoke did not always or not that much increase IEAA, and as such demonstrates the difficulty of detecting these changes when it is clear that OVERALL there is far more bad to smoking than not smoking (J.Calment smoke a 100 years and lived a 122 years...paradox, not, she was protected genetically and did healthy choices despite these bad choices - so it evened out and she still lived on while other chain smokers die at 22 years old of cancer or other complication).
PPS: they said plant diet/lean meat = reduce IEAA/EEAA. Also they said, fish oil/fish meat (which is a lean meat) was also good. Again, the reason there is because fish, is lean first, if a small fish is low in mercury poison/toxin, and second, because it contains fatty acids that retard atherosclerosis and other diseases : DHA/EPA (22:6, 20:5) OMega-3 fatty acids that are incorporated in brain phospholipid mitochondrial membrane's fatty acid composition (omega-3 improve cognitive function and reduce Alzheimer's slightly...pre-Alzheimer's only..), and that's because Omega-3s (18:3 ((alpha/gamma)Linolenic acid), 20:5 (Eicosapentaenoic acid), 22:6 (Docosahexaenoic acid))) are fluidizers of the membrane (they reduce viscosity of membrane kinetic, thus the membrane kinects are 'faster/more watery/flowy/more fluid...less fatty/sluggy or saturated/compact (oily/fat))). Thus, this improves the capacity for 'reactions' to happen in the mitochondria and neuron depend on that - they send electrical impulses they depend on fast mitochondrias that have rapid ATP output and signal response; which means fast kinetics (fluid membrane movement))))). Cholesterol inserted in the mitochondrial membranes helps thjat a lot for it is a fluidizer Also (and hence why our brain is cholesterol filled it is mitos)). Highly active tissues like heart or brain need cholesterol to fluidize, otherwise they rely on Omega-3s especailly, fish oil contains A LOT of them. It helps a lot and why it would be inverse to IEAA and EEAA in this study (and why consuming lean fish rich in O3 slows aging; plus studies of O-3s have shown slowed telomere attrition iwth higher O3 consumption. The only problem with Omega-3 is peroxidation, DHA/EPA is very highly peroxidizable unlike monounsaturates in olive oil (18:1 oleic fatty acid, only one kink, 'Mono' unsaturate). It is why J.Calment consumed tons of Extra-Virgin Olive Oil and has an increase in Monounsaturation in her mitos (and was thus protected from peroxidation problem of hihly polyunsaturated fatty acids such O-3s DHA/EPA (20:5, 22:6, 5 kinks, 6 'double-bonds' makes orders of magnitude more chances of 'being damaged' than one kink (monounsaturate))). Shit demonstrates one more of the vegetal nature of it (olives tree) being better in some cases of IEAA and EEAA.
Just a 2 cent.
PS: typo 'This* demonstrates one more of the vegetal nature of it (olives tree) being better in some cases of IEAA and EEAA.' (yes sh*t demonstrates a lot of things, like me typing for sh*t on this keyboard, sorry).
China is speeding along CRSPR-cas9 trials due to regulatory climate: https://www.wsj.com/articles/china-unhampered-by-rules-races-ahead-in-gene-editing-trials-1516562360