Fight Aging!

This post walks through the process of setting up and running a simple self-experiment - a trial of one - with two compounds shown to improve measures of cardiovascular aging, specifically (a) pulse wave velocity, a measure associated with rising blood pressure and stiffening of blood vessels, and (b) prevalence of oxidized lipids, associated with the progression of atherosclerosis. These compounds work via their effects on mitochondria, dampening the impact of aging on these vital components of cellular function, but without actually repairing the underlying damage that causes aging.

The two compounds are MitoQ, a mitochondrially targeted antioxidant that was shown to beneficially impact oxidized lipids and pulse wave velocity in a recently published small human trial, and Niagen, a form of nicotinamide riboside which also has recent data from a small human trial suggesting that it can reduce pulse wave velocity.

This post, unlike others in this series, focuses on compounds that are approved for use as supplements rather than drugs, are easily purchased and widely used, and already have at least initial human trial data for impact on aspects of aging. That makes it much simpler from a logistics point of view, and thus more suitable as an introduction for people who have not yet tried to rigorously self-experiment. The downside is that these compounds don't address root causes of aging, but are instead at best a way to modestly compensate for the consequences of molecular damage. In this case that means specifically damage to mitochondria and changes in the signaling environment that otherwise cause declining mitochondrial function.

A caveat: one might think that "widely used" means "safe". Safe is a slippery word, however, in that nothing is ever truely safe. Older individuals can and do suffer injury and death from everyday actions, foods, and medications that have no such impact on younger individuals. Regardless of the legions using a particular compound, it is always wise to gently ease into any personal attempt to join them, rather than leaping in at a full dose on day one.

Contents

• Why Self-Experiment with MitoQ?
• Why Self-Experiment with Niagen?
• Caveats
• Establishing Dosages
• Obtaining MitoQ and Niagen
• Establishing Tests and Measures
• Guesstimated Costs
• Schedule for the Self-Experiment
• Where to Publish?

Why Self-Experiment with MitoQ?

Ordinary antioxidant supplements are thought to be, on balance, modestly harmful to long term health. They block signaling that is important to the beneficial response to exercise, for example. Mitochondrially targeted antioxidants, on the other hand, have been shown to slightly slow aging in short-lived species, and improve measures of health along the way. They also appear to be a viable treatment for some localized inflammatory conditions. The theory here is that mitochondria generate oxidative molecules in the normal course of operation that cause damage within the mitochondria themselves, and that in turn leads to dysfunctional cells in which the mitochondria produce a vastly greater amount of oxidative molecules. Delivering a constant supply of mitochondrially targeted antioxidants may either slow down the pace at which mitochondria damage themselves, or dampen the consequences of cells overtaken by damaged mitochondria, or both.

One of those consequences is the bulk export of oxidative molecules into surrounding tissues and the bloodstream, where they react with lipids. Oxidized lipids can cause further harm in all sorts of cellular processes, but of particular interest is the development of atherosclerosis. Oxidized lipids can cause inappropriate inflammatory reactions in blood vessel walls, and some forms can also cause the cells responding to that inflammation to become overwhelmed and die. This is how the fatty plaques of atherosclerosis form, then grow to weaken and narrow major blood vessels. Statin drugs, that reduce blood cholesterol, succeed in slowing atherosclerosis because they reduce the amount of oxidized lipids in the course of reducing the amount of all lipids.

Further, some degree of dysfunction in the vascular smooth muscle responsible for blood vessel contraction and dilation is thought to be caused by rising levels of oxidative stress in aging - too many dysfunctional mitochondria, too many oxidative molecules. This contributes to vascular stiffness and consequent hypertension, cardiovascular disease, and so forth. Suppressing the oxidative consequences of malfunctioning mitochondria may help here as well.

Mitochondrially targeted antioxidants don't solve the roots of these problems. At best, they somewhat compensate or attenuate ongoing mechanisms. They are cheap, however, and if they can produce effects on risk factors for cardiovascular disease that are, say, somewhere in the same order of magnitude as those achieved by statins or drugs that control blood pressure, with minimal side-effects, then they may well be worth using.

Why Self-Experiment with Niagen?

Niagen is a formulation of nicotinamide riboside, a compound shown to beneficially adjust NAD+ metabolism in cells. The outcome is a general improvement in mitochondrial function. To the extent that loss of mitochondrial function is an issue in aging, regardless of the varied causes of that loss, supplementation with nicotinamide riboside can turn back a fraction of that problem. This loss of mitochondrial function is particularly well studied in neurodegenerative disease and muscle aging, as the brain and muscles are two of the most energy-hungry tissues in the body, but there are consequences in all other tissues as well.

The outcome of nicotinamide riboside supplementation that has the most defensible evidence is much the same as the effects of mitochondrially targeted antioxidants noted above, in that it appears to reduce the dysfunction of vascular smooth muscle cells that is responsible for some fraction of vascular stiffening and hypertension. The results of a small human study provide evidence for a modest reduction in pulse wave velocity in older study participants.

As is the case for mitochondrially targeted antioxidants, Niagen supplementation does not reverse the root causes of aging. It compensates for or attenuates one class of downstream consequence, and is thus of limited utility when considered in the grand scheme of things. But if nicotinamide riboside is both cheap and reliable in the production of that limited utility, while producing few to no side-effects along the way, then it can be worth using.

Caveats

While both MitoQ and Niagen are approved by regulators, are widely used, and are accompanied by good human data on effects and side-effects, one must still think about personal responsibility in any self-experiment. Firstly, read the papers reporting on human trials - the effects, side-effects, and dosages - and make an informed personal decision on risk and comfort level based on that information. This is true of any supplement, whether or not approved for use. Do not trust other opinions you might read online: go to the primary sources, the scientific papers, and read those. Understand that where the primary data is sparse, it may well be wrong or incomplete in ways that will prove harmful. Also understand that older physiologies can be frail and vulnerable in ways that do not occur in younger people and that are sometimes not well covered by the studies.

Secondly, the state of knowledge regarding any particular set of compounds is not static. The science progresses. This post will become outdated in its specifics at some point, as new knowledge and new compounds with similar effects arrive on the scence. Nonetheless, the general outline should still be a useful basis for designing new self-experiments involving later and hopefully better compounds, as well as tests involving more logistical effort.

Establishing Dosages

The only definitive way to establish a dosage for a supplement or pharmaceutical in order to achieve a given effect is to run a lot of tests in humans. Fortunately those tests are underway, and enough has been published for MitoQ and Niagen to simply follow the existing studies. Little further digging, extrapolation of doses from mouse to human, or other similar work is required.

The 2018 MitoQ human study used a once daily dose of 20mg for six weeks. The 2018 Niagen human study used a twice daily dose of 500mg for six weeks.

Obtaining MitoQ and Niagen

MitoQ is cheap and readily available from MitoQ Limited via any number of reputable online storefronts. The same is true of Niagen, with numerous sellers listed at Amazon. In the latter case, there is a wide difference in price for essentially the same product from different vendors, so comparison shopping is a good idea.

Establishing Tests and Measures

The objective here is a set of tests that (a) match up to the expected outcome based on human trials of MitoQ and Niagen, and (b) that anyone can run without the need to involve a physician, as that always adds significant time and expense. These tests are focused on the cardiovascular system, particularly measures influenced by vascular stiffness, and some consideration given to parameters relevant to oxidative stress and the development of atherosclerosis.

• A standard blood test, with inflammatory markers.
• An oxidized LDL cholesterol assessment.
• Resting heart rate and blood pressure.
• 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 in a treatment that compensated in some way for the effects of aging on the smooth muscule cells in blood vessel walls - as is thought to be the case for mitochondrially targeted antioxidants. 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 exist 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 Baseline is probably all that is needed for present purposes. But shop around; this isn't the only provider.

Oxidized LDL Cholesterol

The more mainstream blood test services such as WellnessFX don't offer as wide a range of testing as some of the specialists. For example, the Life Extension Foundation maintains a blood test service that includes a test for oxidized LDL cholesterol. Again, shop around. There are others.

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 to gain a more accurate view of the state of your physiology. The Omron 10 is solid: it just works, and seems quite reliable.

Pulse Wave Velocity

For pulse wave velocity, choice in consumer tools is considerably more limited than is the case for heart rate. Again, carefully note whether or not a device and matching application will deliver the actual underlying data used in research papers rather than a made-up vendor aggregate rating. I was reduced to trying a fingertip device, the iHeart, picked as being more reliable and easier to use than the line of scales that measure pulse wave velocity. Numerous sources suggest that decently reliable pulse wave velocity data from non-invasive devices is only going to be obtained by measures at the aorta and other core locations, or when using more complicated regulated medical devices that use cuffs and sensors at several places on the body.

Still, less reliable data can be smoothed out to some degree by taking the average of measures over time, and being consistent about position, finger used for a fingertip device, time of day, and so forth when the measurement is taken. It is fairly easy to demonstrate the degree to which these items can vary the output - just use the fingertip device on different fingers in succession and observe the result. All of this is a trade-off. A good approach is to take two measures at one time, using the same finger of left and right hand, as a way to demonstrate consistency. While testing an iHeart device in this way, I did indeed manage to obtain consistent and sensible data, though there is a large variation from day to day even when striving to keep as many of the variables as consistent as possible. That large variation means that only sizable effects could be detected.

DNA Methylation

DNA methylation tests can be ordered from either Osiris Green or Epimorphy / Zymo Research - note that it takes a fair few weeks for delivery in the latter case. From talking to people at the two companis, the normal level of variability for repeat tests from the same sample is something like 1.7 years for the Zymo Research test and 4.8 years for the Osiris Green tests. The level of day to day or intraday variation between different samples from the same individual remains more of a question mark at this point in time, though I am told they are very consistent over measures separated by months. 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.

An Example Set of Daily Measures

An example of one approach to the daily cardiovascular measures is as follows, adding extra measures as a way to demonstrate the level of consistency in the tools:

• Sit down in a comfortable position and relax for a few minutes.
• Measure blood pressure and pulse on the left arm using the Omron 10.
• Measure blood pressure and pulse on the right arm using the Omron 10.
• Measure pulse wave velocity on the left index fingertip over a 30 second period using the iHeart system.
• Measure pulse wave velocity on the right index fingertip over a 30 second period using the iHeart system.

Consistency is Very Important

Over the course of an experiment, from first measurement to last measurement, it is important to maintain a consistent weight, diet, and level of exercise. Sizable changes in lifestyle can produce results that may well prevent the detection of any outcome using the simple tests outlined here. Further, when taking any measurement, be consistent in time of day, distance in time from last exercise or meal, and position of the body. Experimentation with measurement devices will quickly demonstrate just how great an impact these line items can have.

Guesstimated Costs

The costs given here are rounded up for the sake of convenience, and in some cases are blurred median values standing in for the range of observed prices in the wild.

• Baseline tests from WellnessFX: $220 / test
• Oxidized LDL test from LEF: $170 / test
• MyDNAage kits: $310 / kit
• Osiris Green sample kits: $70 / kit
• Omron 10 blood pressure monitor: $80
• iHeart monitor: $210
• MitoQ capsules from MitoQ Limited: $190
• Niagen capsules from Amazon vendors: $280

Schedule for the Self-Experiment

One might expect the process of discovery, reading around the topic, and ordering materials to take a few weeks. Once all of the decisions are made and the materials are in hand, pick a start date. The schedule for the self-experiment is as follows:

• Day 1-14: Once or twice a day, take measures for blood pressure and pulse wave velocity.
• Day 14: Bloodwork and DNA methylation test.
• Day 15: Start the program of daily doses, and keep that going through the following measurements.
• Day 57-70: Repeat the blood pressure and pulse wave velocity measures.
• Day 70: Repeat the bloodwork and DNA methylation test.

Where to Publish?

If you run a self-experiment and keep the results to yourself, then you helped only yourself. The true benefit of rational, considered self-experimentation only begins to emerge when many members of community share their data, to an extent that can help to inform formal trials and direction of research and development. There are numerous communities of people whose members self-experiment with various compounds and interventions, with varying degrees of rigor. One can be found at the LongeCity forums, for example, and that is a fair place to post the details and results of a personal trial. Equally if you run your own website or blog, why not there?

When publishing, include all of the measured data, the compounds and doses taken, duration of treatment, and age, weight, and gender. Fuzzing age to a less distinct five year range (e.g. late 40s, early 50s) is fine. If you wish to publish anonymously, it should be fairly safe to do so, as none of that data can be traced back to you without access to the bloodwork provider. None of the usual suspects will be interested in going that far. Negative results are just as important as positive results. For example, given the measures proposed in this post it is entirely plausible that positive changes in a basically healthy late 40s or early 50s individual will be too small to identify - they will be within the same range as random noise and measurement error. Data that confirms this expectation is still important and useful for the community, as it will help to steer future, better efforts.