Hi Reader

This is part 2 of an email series I am writing about the life meter: what markers a personalized dashboard for longevity could include.

This week I'll focus on biological age. There is a lot more to say about these tests than I anticipated.
​By the end of this email, you will have a much better idea of what is behind this "hot" topic, if it's worth spending your money on, and if you can trust their claims.

Behind the term biological age is the concept of an age that reflects function rather than number of years.
I am 42 years old, but could have a biological age of 35, or 50, depending on how my body is performing.

Biological age depends on our habits, what we're exposed to and what we eat.

An interesting concept, testing for biological age has become trendy. But is it really worth the hype?

This week I will dive into the different types, the pros and cons as well as the cost. Today's edition is deep in the techy part of longevity. Bare with me, I promise to make it digestible.

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1. Telomere length testing​
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This is sort of the OG of biological age testing. Telomeres are a structure that caps our chromosomes.
It has long been observed that telomeres shorten as we age.
Because of this effect, we could get a biological age by measuring telomere length.
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This also spawned the idea that our cells, perhaps even us as a whole, could live longer by manipulating the length of telomere. These experiments have been inconclusive.
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There are thousands of scientific studies on telomeres and some do show an association between shortening and increased risk of disease. But not causality. Which means that this test can not be used to diagnose or predict.

It's also worthy to note that there is no established length per age (as there is for example VO2max per age) because telomere length can vary tremendously between individuals.
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It also does not only vary in one direction, but telomeres shorten and lengthen. It is not yet fully understood why or what exactly may trigger such response.

Given these limitations, that would not be my test of choice.
But many biohackers and the "quantified self" movement made telomere testing one of their go-to tests for longevity. You may find advocates for this test, especially those who test everything and anything.

I recommend reading this article by aging experts Dr. Elissa Epel and Dr. Elizabeth Blackburn if you are looking for more details on telomere testing and to make your mind. In this article, you can also find a list of companies that sells the test.
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Cost ranges between 300 and 800 USD depending what is being tested.
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2. Epigenetic age

Epigenetic clocks

In 2013, a study led by Dr. Steve Horvath found a specific set of "tags" (called methylation) in the DNA of our cells correlating with age. With an algorithm, Horvath was able to predict the age of the sample donor with great accuracy (96%).

This methylation signature is called the "epigenetic clock". Using this technology, it has been found that different organs in our body tend to age at different pace.

The concept of epigenetic age was born.
With the use of different algorithms to increase accuracy, scientists found a way to quantify the pace of aging.

Because epigenetics (marking of the DNA that regulates genes expression) is influenced by our environment, it has also been established that our lifestyle, behaviors and diet affect this biological age.

For example, tissues from smokers showed a higher epigenetic age than tissues from non-smokers. Something called epigenetic age acceleration.

Similarly data collected on more than 2,100 men and women aged 40 to 92 as part of the Framingham Heart Study showed that for every five-year increase in age acceleration, the risk of dying from any cause during the study jumped by 15% (source).

Another study using this technique found that the epigenetic ages of breast, kidney, lung and skin cancers were 40% older, on average, than the patients from which they were removed (source).

Epigenetic age is strongly correlated with healthspan.

Now the main limitation for this test is that there has not been any study showing that it can predict future health outcome.
Indeed, there are many studies showing a correlation, but done in a retrospective manner: tissue analysis of people with a diagnosis revealed a higher biological age.
But never in prospective manner: where you take samples from people, determine biological age and follow them over time to see if a higher epigenetic age predicts disease.

Clinicians also argues that we don't have the evidence that accelerated epigenetic age leads to shorter lifespan. ​
Because of this, epigenetic age should be used with caution, because it does not predict lifespan.

It's also important to know that there are different versions of the test on the market, with proprietary algorithms to analyze the methylation patterns and this can make a HUGE difference.

I can tell you for example that the last test I used, has been proven to be incredibly inaccurate.
​In 2021, a study came out showing that a 8-week lifestyle program resulted in a decrease of biological age of 3 years on average. I was all over it! A peer-reviewed study establishing age-reversal with a lifestyle intervention was unheard of.

I ordered the test and even created a business partnership with the Canadian company that manufactures it.

Then, this very study was discussed by one of the leaders in the field, Dr. Morgan Levine, in a conversation with my favorite longevity expert Dr. Rhonda Patrick, about 1 year after the study was published.

From her, I learned that the algorithm used in the study was not powerful enough to remove background noise (DNA methylation that happens but does not predict age, or artifacts from the PCR).

Dr. Morgan Levine stated "It was all noise". This claim that the epigenetic age was reduced by 3 years was simply inaccurate.

What a let down.
Not all epigenetic age tests are created equal.

Dr. Ftizgerald, a naturopathic doctor, has since then published some case studies from this cohort with an updated analysis, using the most powerful algorithm available.
So I don't think her work should be completely dismissed. I linked the study for you, so you can go look at the diet people were following. Her book Younger You also has the entire method.
There are many people reporting great success in her program.

However, the question I am left with about epigenetic age is this : her intervention and diet seem to be significantly affecting methylation, but... is it the same as affecting aging?

This is another chicken and the egg situation. We don't know if this epigenetic clock is a result of aging or if it is upstream of functional changes that truly influence the rate of aging.

Something else to keep in mind when using these epigenetic tests, is that some research has found that epigenetic age can change by more than 3 years from day to day in apparently healthy individuals without intervention.
So what does that mean for the value of this test?

For a list of the epigenetic age tests available, I recommend this page.​
Cost: $230-500 USD + shipping and customs if outside of the US.

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Epigenetic speedometer

One method took this idea of an aging rate one step further: the DunedinPACE.

Here is how the test was created using data from the Dunedin cohort, as explained by its author, Dr. Daniel Belsky,
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"The DunedinPACE was created with the biological age of different indicators of function, or integrity, of multiple organs in the body of participants, on repeated occasions over 12 years in a first study and for 20 years in a follow up study.
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All the markers are then "composited" into a single index, and normalized to a value of 1, representing the amount of change that we would expect to see in the passage of one year.
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Then taking 3-4 different time points, the data from each individual is compared to evaluate how fast change is occurring."
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​The DunedinPACE provides a number between 0.6 and 1.4: a value under one if aging occurs slower or over one if aging occurs faster. ​
When thinking about this pace of aging in terms of percentage, that means aging 40% slower or 40% faster than the norm.

This test has gained in hype because of its use by the millionaire whose goal is to live forever, Bryan Johnson, and his contestants in the "Rejuvenation olympics".

To use the DunedinPACE algorithm, visit this company.
Cost: $230 USD (+ shipping and customs if outside of the US)

Note: this test makes sense when re-testing regularly for a rate. Isn't that a convenient set up to sell a product?

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3. Glycanage

There is another one of these biological age markers: glycans.
Proteins that belong to our immune system called Immunoglobulins change with age. They become more glycosylated, which means more coated with sugar molecules.
There are many different immunoglobulins, and different types of chemical reactions adding sugar to these proteins.

An index called GlycanAge was created by combining three of them, that correlates at 60% with chronological age.
The predictive power of this marker goes up to 70% when used in combination with blood pressure.

Knowing that epigenetic clocks correlate at 96-98%, this means that the link between glycanage and biological age is not as tight and leaves more room for speculation on what may be going on.

Perhaps the most interesting aspect of this test is that it looks at the immune system and could reflect inflammation levels.

Influenced by a diet high in fat and showing that women age 50% faster for 5 years after menopause, this marker seems to be more closely linked to some very specific biological events than others. I wonder about a biased effect that could cloud the results or at least need to be considered when using this test.

​GlycanAge website​
Cost: £289 (approximately $370 USD)

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4. Your longevity coach summary​
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It can be fun and interesting to measure your biological age. Being directly available to you as a consumer is empowering and motivating when creating longevity lifestyles. It gives you an experiment mindset: test, modify behavior, re-test.

They can be a useful tool when wanting to know whether we may be doing something that ages us faster, or slower. Although they are probably best used when in combination with a tool to pinpoint what it is that we are doing that ages us faster or slower (like this one).

However, when making changes that do influence biological age, there is no evidence that it could influence how long you live. Does it really give us much more than a number on "how we feel"?

When choosing a biological age test, epigenetic age are the most accurate. However, make sure to use "3rd generation" algorithms such as DNAge, PhenoAge and GrimAge.

These tests are costly: 350-500 USD, and when creating longevity lifestyles, may be more interesting when taking them regularly to evaluate how you're doing.
So you need a budget of 700-1000 USD to test twice a year. When taking the tests from outside the US (I live in Canada), additional fees apply for shipping and customs.

The anti-aging industry and biohackers of this world will tell you that this is an "undeniable tool for longevity".

After learning so much about epigenetic tests, from the time they were first published until now, even using them myself, my personal take on them is that they are interesting if you have a large budget for your health, but are neither the most predictive of longevity, nor the top priority in your health spending.​
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For most people interested in longevity, 700-1000 USD are better spent on a coach (Hi!), gym membership/equipment, some wearable to track your sleep, high quality protein or access to the sauna.

These biological age tests could be an interesting addition to your longevity dashboard.

But they do not replace a VO2max or muscle strength when it comes to predicting how old and how well you will age.

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And we're through!

Thanks for reading this tech-heavy edition of the newsletter. You can click below to let me know how I did today.
Your feedback is important to me.

I truly hope this provided a comprehensive view of biological age.
If you decide to test it, let me know about it!

Talk soon.

Jihane

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