The Age of Rejuvenation: Decoding Biological Age Clocks for Ultimate Health
From Vanity Metric to Healthspan Expansion: The Role of Biological Age Clocks
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A few months ago, entrepreneur Bryan Johnson, known for his fascination with immortality, launched the "Rejuvenation Olympics," a unique competition challenging participants to reduce their biological age as much and as quickly as possible. The concept of “biological age”, a pivotal metric in longevity research introduced by Steve Horvath in 2011, serves as the foundation for this contest. Since its inception, the “biological age” marker has not only gained traction in clinical research but has also become a popular offering on various wellness platforms and services - at times becoming one of these hot “vanity” heath metrics (like HRV, etc.) biohackers like to brag about.
A couple of years ago, driven by curiosity, I took my first biological age test—back then, it revealed I was 38, a year older than my chronological age of 37. At that time, the result didn't strike me as particularly useful, mainly because I had not yet started to actively optimize my health. Recently, as I became eager to reassess my biological age, I've encountered a lack of clarity regarding the scientific validity of biological age offerings and the tangible benefits they offer. This article is an attempt to navigate through this, shedding light on the science and business driving it and (healthily) scrutinizing the promise it holds for extending human healthspan. Buckle up.
What’s biological age and why does it matter?
What’s biological age?
In its most widely adopted definition, biological age is your body’s internal age as opposed to your chronological age, the amount of time since you were born. Biological age “reveals the efficiency at which your body - down to your cells - is working, and how well it should be working given your chronological age“. A notable example of this idea in action is Bryan Johnson, the immortal millionaire who became famous for lowering his biological age to 18, despite being 45 years old.
Biologically, we all age at a different rate. This explains why some people look and feel young well into their senior years while others struggle with aches, pains and other issues in the supposed prime of their life.
Why is biological age important?
Then, we can understand why biological age is a better marker to evaluate our “real” health: biological age - rather than chronological age - IS the primary risk factor for the majority of chronic illnesses (from most forms of cancer, to dementia, cardiovascular disease, metabolic disorders, glaucoma, sarcopenia, etc) and is also better marker for how we feel and look.
As a marker, biological age is now pretty fundamental to Longevity research. It is being used to investigate the biological aging mechanisms, measure how efficient aging and aging-related diseases treatment strategies are, as well as predict/prognosticate the onset of various diseases. At the individual level - biological age is used to determine personalized risk, and if a person is undergoing accelerated or decelerated aging: it looks at the damage done so far and, depending on the approach used to calculate biological age (as we will explore later), it can also act as a feedback loop to understand whether some interventions - such as lifestyle changes - are driving a reduction in the pace of aging.
Overall, biological aging “clocks” are expected to be useful for studying what causes aging and what can be done against it.
How are we aging? The crucial role of epigenetics in biological aging
What causes aging? Contrary to popular belief, our lifestyle does: only 20% of the aging process is determined by our genes, and 80% by our lifestyle. Everything from our diet, quality of sleep, and stress levels to our environment, alcohol consumption, and the amount of exercise we do directly affect how well or poorly we age. More specifically, our lifestyle causes changes to the way our genes work, a mechanism that’s called the “Epigenome”. Therefore, the Epigenome is central to biological aging, which is why many methods for assessing biological age - which we will cover below - focus on assessing it.
How can we measure biological age?
In 2011, Steven Horvath's research team at UCLA pioneered the first epigenetic clock based on human saliva. Since then, there has been dozens of new discoveries and approaches to measuring biological age, which vary in degrees of accuracy, precision, and use.
Currently, there are three main ways to measure biological age:
molecular, which examines aging at the molecular or cellular level through markers like DNA methylation or glycans
phenotypic, focusing on the function of specific organs within the body
functional, assessing physical abilities associated with aging, such as body composition or facial aging indicators
Since functional tests assess aging in much later stages, we’ll only focus on molecular and phenotypic age clocks in this post.
1. MOLECULAR CLOCKS
🕒 DNA methylation (also known as “Epigenetic Clocks”)
DNA methylation is a chemical modification to DNA that can turn genes on or off for proper cell functioning. As we age, this methylation process goes awry (impacted by age, lifestyle, and environmental exposures), leading normally silent genes to become active - like pro-inflammatory or tumor-promoting genes -, while healthy genes become silenced. DNA methylation “clocks” - which is how we call algorithms to measure aging - analyze large sets of DNA methylation data across many “sites” in your body to determine how old you really are biologically, based on saliva or blood test samples.
The study of DNA methylation has made quick strides, with and many clocks have been introduced since Steve Horvath's 2011 discovery. The newest, called "3rd generation clocks” shows most promise, particularly the DunedinPACE - which Bryan Johnson uses in his Rejuvenation Olympics.
What are the leading DNA Methylation clocks?
The DunedinPACE is currently acknowledged to be the most robust in the scientific community:
It has robust scientific evidence. With high reliability and reproducibility data, it is supported by 45+ published studies and 30+ longevity scientists’ labs
It is comprehensive. It looks at DNA methylation cross 173 “sites” in your body (cardiovascular health, dental health, etc.) as opposed to a much fewer number of sites in other clocks.
It is the most actionnable. Instead of merely assessing a person's biological age, DunedinPACE evaluates the "pace of aging" — the rate at which a person ages each chronological year. (for example, 0.90 implies 10% slower aging than average, while 1.05 implies 5% faster aging). This measure is not just more precise on an individual level; it's also more practical: pace of aging responds to lifestyle interventions. Meaning you can see real-time effects of dietary shifts, exercise regimes, and other lifestyle changes to improve healthspan and lifespan quicker and more distinctly with DunedinPACE.
The GrimAge clock (developed by the father of biological age clocks Steve Horvath) is another clock renowned for its accuracy and strong correlation with mortality - however, it measures biological age without assessing the aging pace or responding to interventions, unlike the DunedinPACE, which does both. While numerous other DNA methylation-based clocks exist, such as David Sinclair's recent Tally Health or Elysium Health’s Index test, they fall short in reliability and scientific evidence compared with the DunedinPACE.
Learn more about the DuneInPACE algorithm and the different generations of clocks, here. Get a DunedinPACE at TruDiagnostics (Available in Europe and the US), or Novos (US only)
🕒 Glycans (also known as “Glycan Clocks”)
Chronic inflammation (also called “inflammageing”) is one of the 12 “Hallmark of aging”. A novel approach in assessing inflammation in our body involves measuring markers called glycans. They are complex carbohydrate/ “sugary” molecules, which are among the four fundamental components of cells alongside DNA and proteins and form a coating on our cells.
Glycans have become an innovative marker for assessing both chronic inflammation and aging. Specifically, glycans attached to our immunoglobulins (IgG) are known to predict future hospitalization from a wide range of diseases, particularly metabolic diseases [1]. Multiple studies suggest that, by examining glycans associated with the immune system and chronic inflammation, it is possible to accurately determine an individual's true biological age.
What’s the leading Glycan clock? GlycanAge, the company started by the father of glycans research Gordan Lauc, has pioneered an aging biomarker test to determine your biological age examining glycans, gathered through finger prickling. Though still a novel approach, its advantages are:
It is actionnable. Glycans are influenced by external factors such as environment and lifestyle choices and respond to interventions within a timeframe of 3-6 months - similarly to DunedinPACE (although from a very different mechanism), they provide a personalized feedback loop on how your lifestyle interventions impact your GlycanAge.
They are prognostics aids. Glycans change 7 to 10 years before diseases occur - GlycanAge can point to early signs of some major chronic diseases such as diabetes, cardiovascular disease, and autoimmune disorders which are helpful in personalized medicine.
Learn more about Glycans and GlycanAge here, You can get a GlycanAge test on GycanAgeMetabolism (also known as “Metabolic Clocks”)
2. PHENOTYPIC CLOCKS
🕒 Metabolic clocks
Another method involves analyzing various metabolic blood markers (and therefore biological functions in the body) through a straightforward routine lab test to estimate biological age, known as "metabolic clocks". This is an increasingly popular approach in preventative health: advanced blood testing companies like Inside Tracker all offer a biological age or age score through a “metabolic clock”.
This method looks at the correlation between specific metabolic blood markers (such as LDL, fasting glucose, etc.) and mortality risk to determine the individual's biological age - through an algorithm: it looks at intrinsic markers of biological aging, rather than direct markers, contrary to the epigenetic clocks outline above.
What’s the leading metabolic clock? The issue with metabolic clocks is that there are pretty much as many clocks as there are companies offering them: each company has crafted its unique algorithm.
This comes with limitations: first their accuracy can vary significantly, and these clocks may not be as precise due to their indirect nature and dependence on the fluctuations of the individual biomarkers they measure — unlike epigenetic clocks, which measure only one biomarker or aspect of the cell. Second, these biological age algorithms are not yet supported by robust scientific evidence.
However, they are helpful navigational aids for patients. These metabolic lab tests usually cover between 40 to 100 biomarkers: consolidating this information into a singular "biological age" metric provides a simplified yet helpful view to patients on how well they are doing.
You can get your metabolic test & metabolic aging clock on InsideTracker
So, should you test your biological age, and how?
At the clinical level, it’s important to note NONE of the clocks - not even the acclaimed DunedinPACE - have been clinically validated yet. This is their stated goal, though: biological clocks are to become the definitive biomarker for aging in a not-so-distant future:
“Epigenetic clocks will never replace clinical markers, [but] the clocks add value to them. I think 5 years from now we will have human blood-based clocks that are so valuable that they could be used clinically” - Steve Horvath (source)
Currently, DNA Methylation/epigenetic clocks are being used alongside other standard markers into clinical trials, where the practice of using multiple clocks and calculating the average age reduction across them addresses concerns about accuracy. There is optimism that they will only continue to improve and become the gold standard.
On an individual level, prioritizing a standalone biological age test without first attending to your regular health check-ups, such as routine blood work, is obviously not advisable: you should first make sure you are doing the ‘basics’ for your health before delving into how well you’re aging.
Choosing to find out your biological age may provide valuable insights for some, but for others, it could become another aspect of their health to fixate on. When this metric is added to the mix of other health data from wearables, blood tests, and beyond, it can ironically heighten anxiety. Consider how you'd react if your wearable device indicates poor HRV and sleep quality; how would a bad biological age affect you?
For many people I know, the drive to get their biological age stems from curiosity (and dare I say at times, perhaps a touch of vanity?). This is missing the point of the real value of biological age - exemplified by Bryan Johnson’s Rejuvenation Olympics -: to evaluate how your efforts towards healthy aging are paying off. Biological age clocks offer unique, tangible feedback loops that validate whether the difficult choices you make daily to optimize your healthspan are actually making a difference. In the field of behavioral science, such feedback loops are crucial for encouraging behavioral change - this is the promise of these innovative clocks.
“You should take a blood-based biological age test if you are motivated to make lifestyle changes and want to target signs of aging,” says Dr. Blander.
Final opinion? You should get a biological age test if you want to measure the impact of your lifestyle changes on your biological age and biological age is a metric that motivates you (otherwise, there are many other foundational health metrics you can follow).
NB: Thanks to Nikolina Lauc from GlycanAge for her guidance and insights that helped ensure this article is accurate. Her expertise in biological aging clocks has been invaluable.
Disclaimer: I hold investments in GlycanAge and Novos, mentioned in this article.
⭐ Introducing "What I'm Reading": a new section where I'll share the books and articles enlightening and inspiring me in each edition ⭐
Cancer Is Striking More Young People, and Doctors Are Alarmed and Baffled - WSJ
Global cancer burden growing, amidst mounting need for services - WHO
“Ovaries are an enigma that could unlock human lifespan” - FT
“First FDA-approved psychedelic drug could come as soon as 2024” - Healthcare Brew
Closing the women’s health gap: A $1 trillion opportunity to improve lives and economies - Mc Kinsey