“Knowing what we are, we shall know how to take care of ourselves, but if we are ignorant we shall not know.”

—Socrates, First Alcibiades

“Know thyself” is an invocation as old as the Oracle at Delphi, but when it comes to human life extension, that invocation isn’t just important, it’s a fundamental requirement.

If you don’t know your own body before starting on specific longevity interventions—like taking new supplements you just learned about from some longevity podcast, life-extension blog, or anti-aging book—you could easily do yourself more harm than good.

For instance, did you know that people with asthma who have the WDR46 gene are possibly at a higher risk for Aspirin-Exacerbated Respiratory Disease?

Given that aspirin, especially for men, is an oft-touted longevity molecule (it’s one of the supplements found by NIH’s Interventions Testing Program to prolong life in male mice), anyone with the WDR46 gene needs to be incredibly careful before embarking on a life-extension regimen that includes a daily aspirin (I mean, probably don’t).

And this is just one example that illustrates the benefits of genetic testing and of knowing a whole host of your other biomarkers.

Understanding yourself, your body, your genes, your hormones, your gut health, your blood sugar, and more is critically important for personalizing your anti-aging routine safely and effectively.

Which is why—starting with this piece and continuing for the next few weeks—we’re publishing a new article series on Longevity Advice all about how best to “Know Thyself.” Or more specifically, “Quantify Thyself.”

Longevity and the quantified self

This kind of self-measurement, also referred to as “quantified self” or “biotracking” and which is foundational to practices like personalized medicine is, in our opinion, the first step any new spanner interested in extending their own healthspan should take.

“This kind of self-measurement [is] the first step any new spanner interested in extending their own healthspan should take.”

So now that we’ve spent the last few articles identifying the best places and people to learn about longevity science from, the next step on our journey into radical human life extension has to be self-measurement.

Over the next few weeks, you can expect to see articles from us covering the gamut of the quantified-self space, from what medical diagnostics (like blood tests) to get, to fitness wearables and other health monitors, to diet tracking software, sleep apps, and genetic tests, plus how to interpret and use all that data you’ll be getting from this biotracking.

And because your DNA is the personal health data that determines all the rest, it’s the logical place to start.

This first quantified-self piece will cover why DNA is important to understand, how DNA testing works, and the benefits of genetic testing for life extension. 

The next genetics article will compare the best DNA tests currently on the market to give you the information to select the right one for you, and the third article in the series will compare the top “after-market” DNA analysis services that help you interpret and take action from the genetic data provided by these DNA tests.

So let’s begin!

Genetic testing for longevity

In order to really understand DNA testing and genetic testing you need to have a basic understanding of DNA, how it works, and how it’s structured into genes.

If you already know all that stuff feel free to skip ahead to the “What is a DNA genetic test?” section!

What is DNA?

You probably remember the essentials about DNA from your high school biology class, but here’s a quick refresher.

DNA stands for “DeoxyriboNucleic Acid,” which, broken down, means:

• Deoxy: Not as much oxygen as regular ribonucleic acid.
• Ribo: Short for “ribose,” a sugar molecule.
• Nucleic: Residing in the cell nucleus.
• Acid: A molecule that can donate a proton (the opposite of a base, you remember high school chemistry too, right?). Acids are key building blocks to life; amino acids—a different acid type than nucleic acid—when chained together create proteins which do pretty much all the important activities in our bodies. That’s why you see bodybuilders chugging “branch chain amino acid” (BCAA) supplements all the time.

DNA forms a ladder-looking structure that’s then twisted a bit into a double-helix shape. The outside supports of the ladder are made up of those de-oxygenated ribose sugar molecules (plus a phosphate group that sticks them to each other). 

The “rungs” of the ladder are made up of pairs of four different “nitrogenous bases” (a molecule with a nitrogen atom that has the chemical properties of a base). These are adenine (A), thymine (T), cytosine (C), and guanine (G)—the famous “ATCG” DNA letters you may be familiar with.

One of the halves of these rungs, plus the sugar/phosphate support (sometimes called the “backbone”) put together is called a “nucleotide” (yes, sorry, this terminology is actually useful for when we discuss how DNA testing works).

When you combine the nucleotides vertically (i.e. connecting the outside ribose/phosphate supports/backbone to each other) you get single DNA strands (also called polynucleotides), and when you connect two single DNA strands horizontally at the “rungs” (the nitrogenous bases) and twist, you get the familiar double helix ladder shape.

Now, certain bases will only pair up and connect with other bases. So “A” and “T” will only ever pair with each other, and “C” and “G” will only ever pair with each other. This structure—one full rung with its corresponding outside support backbone—is called a base pair because it’s a pair of nitrogenous bases (I told you this overview would be… basic ?).

What’s interesting is that both sides of the DNA ladder, the single DNA strands, actually encode the exact same biological information. They’re not exact copies, but if you separate the strands in the middle you can “read” one DNA strand and be able to reproduce its counterpart. This process is exactly what happens when a cell replicates.

And it makes sense, right? If I have a sequence on my single DNA strand of, say, “AGGTC,” and I know A only pairs with T, and C only pairs with G, then I know the complementary DNA strand must read “TCCAG” for the two halves to be able to fit together. 

Ok, so that’s the basics of DNA, now let’s look at how lots of DNA gets structured.

What are genes?

Genes are specific stretches of DNA strands (of differing lengths: some are only 300 letters long while others are millions) that, when “turned on,” tell the cell to manufacture certain types of proteins. Humans have about 19,000 total genes.

One other important thing to know about genes so you can better understand the different DNA tests on the market is that genes are split up into two parts: exons and introns.

Exons are the parts of the genes that actually code for the making of proteins, while introns are stretches of DNA strands in between exons that are cut out during the protein-encoding process. 

Think of a film strip for a movie, where the exons are the important scenes that move the plot forward, while the introns are the “B-roll” filler you could cut out without losing any of the story.

It’s thought that introns serve the purpose of allowing a single gene to code for several different proteins by being able to be cut apart without losing any exon information, and then spliced together in multiple different ways.

All of your genes’ exons together are called the exome (this word will come in handy when we discuss the different benefits of genetic testing, promise).

DNA strands of genes are typically stored in the nucleus by being tightly wrapped around proteins called histones (like a garden hose around a reel, or thread on a spool) which, when chained together into a tightly packed rope of histones and DNA strands, is called chromatin.

Chromatin all coiled together is then called a chromosome and each person has 46 of them (23 pairs—so now you know why 23andMe has the name it does) floating around in each cell nucleus. There are 22 pairs of “autosomes” and one pair of sex chromosomes: two “X” chromosomes in females and one “X” and one “Y” in males. 

All of your chromosomes added together are called your genome.

In order for a gene to be “turned on” so it can be expressed and tell the cell to make specific proteins, it needs to be unrolled from the histones so a transcription protein can “unzip” and read it. Any gene not unrolled is “silent,” and won’t impact the cell it’s in.

This specific way DNA and genes are packaged around histones (plus some other factors) is called epigenetics. Epigenetic factors can actually change based on lifestyle and environmental factors, including age.

Epigenetics is how we get different kinds of cells in our body. A liver cell has certain liver protein-producing genes turned on while the rest are turned off. The process is the same for a skin cell, or a blood cell. 

It’s also, incidentally, a possible explanation for why we age (one favored by Dr. David Sinclair of Harvard). As the number of accumulated errors in the epigenome grow over time (like a well-loved but scratched CD, so the theory goes), cells start to “forget” what kind they are and can die off, become dangerous zombie senescent cells, or worse, become cancer cells.

So now you’ve got the basic overview of DNA, genes, and chromosomes, let’s get into how to actually learn about your own genome.

What is a DNA genetic test?

A DNA test is a method by which some or all of your genetic data, like the presence of certain genes, or the exact sequence of nitrogenous bases (ATCG, remember?), is extracted and read.

Though, as it turns out, that’s actually a really complicated, difficult thing to do.

To extract the DNA first you need a biological sample—usually saliva or blood with humans.

Then the DNA strands are separated out from the cell nucleus and concentrated into a solution.

What happens next is, again, complicated but, essentially, the DNA strands are separated down the middle, and usually also cut down into smaller lengths.

Because DNA strands are about 40,000 times smaller than the width of a human hair this is, again, really hard and requires specialized equipment and chemistry.

Then the DNA strands are reconnected to other, synthetic, DNA strands.

Depending on the type of DNA test being done these synthetic strands could be ready-made with nucleotides in a pre-set order (like in microarray genotyping), or they could be created on-the-fly by adding individual synthetic nucleotides to the DNA strand being examined (as in genome or exome sequencing).

These synthetic DNA strands are made up of nucleotides with a fluorescent dye added. Each of the four nitrogenous bases is assigned a different color. So A may be green, while C is blue and so on.

A laser then excites these synthetic nucleotides and a high resolution camera records the order of the colors their fluorescent dye gives off. 

So if your camera records say, “blue, green, green, red” you know those colors correspond to “C, A, A, T” on your synthetic, glowing DNA strand. That means you know the original strand must read “G, T, T, A” (since, remember, A only binds with T, and C only binds with G).

Pretty clever right?

Now you have a basic understanding of how DNA tests work, let’s talk about the different types of tests you can get before covering the main benefits of genetic testing.

What are the different types of DNA tests?

There are actually a lot of different types of DNA tests out there but they break down generally into two buckets: genotyping and sequencing.

With genotyping—the kind of test 23andMe and Ancestry do—you’re typically using a DNA microarray chip to look at a limited set of gene types that you may or may not have.

Genotyping is usually cheaper and faster than sequencing because you’re not reading every individual base in a DNA strand (remember from above: you’re binding whole, pre-made synthetic strands rather than adding each synthetic nucleotide one-at-a-time) and because typically only a limited number of sites on the DNA are actually tested. 23andMe, for example tests ~700,000 positions, which is less than ~0.1% of the over 3 billion base pairs in your genome.

In contrast, DNA sequencing methods read the exact sequence of nucleotide bases (ATCG) in your DNA.

Sequencing usually costs more and takes longer (up to a week on modern machines) because every single individual base is being read and recorded, and often re-read as many as 30 times to minimize errors.

Within each of those two buckets are a whole host of specific types of DNA tests.

For instance, within genotyping you can get:

• Autosomal DNA tests: Testing the genes within your 22 autosomal chromosomes.
• Mitochondrial DNA tests: Testing genes present in your mitochondrial DNA (DNA that resides inside mitochondria in the cell instead of in the cell nucleus).
• Y-DNA tests: Testing the genes within your Y chromosome (only for males, obviously).

And within DNA sequencing you can get:

• Whole genome sequencing: Reading your entire genome: every chromosome, gene, and DNA strand down to the individual base letters.
• Whole exome sequencing: Reading all of your exons (see, I told you that word would come in handy!), which is about 1% of your total genome.
• Targeted genome sequencing: Reading a specific part of your genome, often a single chromosome or gene, usually to check for specific diseases or mutations.

So with all these different tests and methods and data out there, why even bother getting a genetic test for longevity? 

What are the benefits of genetic testing that spanners interested in radical life extension should understand?

Benefits of genetic testing for longevity

The benefits of genetic testing go way beyond learning who your ancestors were or connecting with that long-lost cousin living in Bangladesh.

In fact, genetic testing is being used more and more in a clinical setting to help doctors identify diseases, understand and target different cancers, and tailor medical therapies to individual patients.

Even the limited genotyping tests you get to understand your family tree often capture useful health information these days. For instance, both 23andMe and Ancestry can now tell you if you have a BRCA1/BRCA2 gene variant that puts you at increased risk for developing breast and ovarian cancer.

And the good news? 

Forewarned is forearmed. Genetics aren’t destiny. If you know you’re at risk for certain conditions, you can plan and alter your lifestyle, diet, and exercise in order to alter your epigenetics (remember that word?) that control gene expression.

The benefits of genetic testing for longevity thus are several:

1. Disease prevention

Longevity is about preventing diseases that result in decline and death, not just about using the right supplements or eating the right superfoods. This means getting early warnings about things like Alzheimer’s, Parkinson’s, cancer, and heart disease can allow you to work to prevent them.

Especially those last two, as heart disease and cancer are, by several times, the top two largest causes of death in the United States.

And it should come as no surprise that genetics play a big role in your risk for cancer and heart disease. Understanding what you may be at risk for, and adjusting your lifestyle accordingly, can alter your epigenetics to give you the best chance of avoiding, or at least delaying, those diseases.

2. Better-tailored longevity interventions

Everybody’s genetics are different, and so it stands to reason that longevity treatments will affect people differently.

Life-extension interventions that may work for me won’t be as effective for you. We already know this to be true between males and females: for instance, rapamycin increases lifespan more in female mice than male mice.

Is aspirin a good longevity intervention? Or, as in the example given way back at the beginning of this article, is it a dangerous disease trigger?

Knowing your own DNA means you can make better, more informed decisions about different life-extension treatments and therapies and have a more full understanding of the actual risks involved for you as an individual.

3. Identifying existing health issues

One benefit to genetic testing for life extension not often discussed is the possibility of identifying, not just the risk for future diseases and ailments, but health issues you already have and may not know how to treat.

For instance, certain gene variants can lead to vitamin deficiencies, enzyme dysregulation, and a whole host of other issues that may be causing health problems you didn’t even realize you had.

Being able to identify these health issues is the first step to treating and dealing with them.

What type of DNA test should I get for longevity?

So after all that, what kind of genetic test should you get for life extension?

I’ll be covering that question in more detail in two weeks when we compare the top DNA tests currently on the market but, as a sneak peek, I personally plan to go with whole genome sequencing.

Your specific circumstances may be different, however for me whole genome sequencing makes the most sense for a couple reasons:

1. The price has come down significantly from even a few years ago, and many companies offer whole genome sequencing for under $1,000 (with several even offering promotions in the $200-$400 range).
2. The data you get is so much more comprehensive than the consumer genotyping tests on the market right now, and can be uploaded to many different 3rd party analysis tools to learn all sorts of different things you can’t get from a typical genealogy DNA test.
3. Our understanding of DNA and genes is still evolving rapidly, and by having all my genetic information to hand I can take advantage of any new discoveries of important genes or variants without having to get a new test every time.

Additional benefits of genetic testing for longevity

Thanks for sticking with me for the past 3,000 words. I’m sure there are other benefits of genetic testing for longevity that I wasn’t able to cover, so if you’ve got genetic testing done I’d love to hear why in the comments. 

Stay tuned next week when we take a break from genetics to look at the importance of sleep tracking for longevity!