How Old Are You?

??In this Nexus:

?? Chronological vs. biological age

?? Testing your biological age

?? My fitness age

?? The most accurate biological age testing method

?? Different epigenetic clocks

They say it is impolite to ask someone's age, so I do not expect you to comment and disclose yours. However, I want to raise a question, do you know how old you actually are? You might say it is a silly question, but what is written in your passport might not be true. How come? Think of this. Have you ever been in a situation, when you get to know someone's age and you are just surprised how much younger (or older) that person looks? Well, that is when the 'biological age' term comes into the discussion. In this Nexus I will explain the difference between chronological and biological age, how biological age can be measured and what are the most accurate methods to define it.

Chronological vs. Biological Age

When discussing age, it's common to differentiate between various types based on biological processes, legal definitions, and social constructs. While talking about longevity, the most important ones are chronological and biological age. There is a clear distinction between those two, as well as there can be a significant difference between your age based on the time of birth and how old your body actually is.

The visual above describes the difference between the terms of those two age types. Chronological age is the universal standard for legal and societal purposes, such as determining voting eligibility, retirement age, and age-specific rights or responsibilities. In the meantime, biological age is an assessment of physiological and cellular health and can vary significantly from one's chronological age, influenced by genetics, lifestyle, diseases, and environmental factors. Biological age is thought to be a better predictor of disease risk, life expectancy, and overall health than chronological age.

There are other types of age, like psychological age, defining how old or young a person feels mentally and emotionally, functional age, determined by an individual's physical and cognitive abilities, considering how well they can perform activities of daily living, and social age, reflecting the societal and cultural norms about behaviours, roles, and relationships expected of people at different life stages. However, these 3 are not in scope of this Nexus .

Testing Your Biological Age

Testing biological age, which as mentioned may differ from chronological age, involves assessing various aging-related biomarkers (i.e. biological molecules found in blood, body fluids, or tissues that can be used to indicate health or disease state). These tests can provide insights into your health, wellness, and the aging process, their reports can also provide recommendations on how to change some of your lifestyle elements in order to slow aging. Below I have listed several currently available options for testing biological age:

1. Epigenetic Clock Testing (1 ): This method assesses the methylation status of DNA to estimate biological age. DNA methylation is a biochemical process involving the addition of a methyl group to the DNA molecule, which can alter gene expression without changing the DNA sequence itself. DNA methylation patterns change with age, and certain algorithms can predict biological age based on these patterns. Such tests typically require a blood sample.
2. Telomere Testing (2 ): Telomeres are the protective caps at the ends of chromosomes, and their length is considered a good indicator of cellular aging. Shorter telomeres are associated with aging and increased risk of diseases. Currently available tests involve analyzing blood or saliva samples to measure telomere length.
3. Metabolomic Testing (3 ): This approach analyzes small molecules in the blood, such as amino acids, vitamins, and other metabolites, to define biological age. Changes in the levels of these molecules can reflect the body's metabolic state and age-related changes.
4. Proteomic Testing (4 ): Similar to metabolomic testing, this method evaluates the levels and types of proteins in the blood to estimate biological age. Proteins play crucial role in cellular processes, and their composition in the body changes with age.
5. Phenotypic Age Calculators (5 ): These tools estimate biological age based on various clinical biomarkers obtained from blood tests, such as white blood cell count, albumin levels, and glucose levels, combined with physiological measurements like blood pressure. They use statistical models to predict biological age.
6. Microbiome Testing (6 ): The composition of the gut microbiome changes with age, and some tests analyze stool samples to assess the diversity and types of microbes present. This can provide indirect insights into biological age and overall health.
7. Online Questionnaires and Algorithms: Some platforms offer assessments based on lifestyle factors, medical history, and physical fitness levels to estimate biological age. While these are much less precise than biochemical tests, they can provide a general overview of your aging process in relation to lifestyle choices.

These tests vary in their specificity, accessibility, and the type of information they provide. Worth mentioning - the price varies as well and some of these can be quite costly. I haven't done any of these tests yet, but the one I've chosen after some scientific research and extensive investigation of reviews costs around 300 USD (epigenetic clock test from blood). Will share my experiences as soon as I resolve to do it.

My Fitness Age

On daily basis I like to check my fitness age calculated by Garmin watch combined with the measurements of Garmin smart weights. It is based on the intensity of physical activities, resting heart rate and body fat percentage or body mass index (whichever is available). According to my watch and weights, on the day I am writing this blog I am 27 years old (instead of 34 according to my passport). Quite motivating, even thought not as accurate as the blood tests.

What Does Science Say?

The Most Accurate Biological Age Testing Method

So what is the most accurate biological age testing method to date according to the available scientific data? Based on the review published in the journal of EBioMedicine (7 ):

• Telomere length is extensively validated in numerous non-clinical and clinical studies (1000+ studies), but has low predictive power. While telomere length reflects cellular aging, this method has limitations due to variability in telomere length across different cell types and less direct correlation with age-related health outcomes.
• The composite biomarker (proteomic testing) is not validated enough but has the potential to be a stronger predictor than telomeres, as is the Metabolic Age Score.
• The epigenetic clock currently performs the best considering both aspects, i.e. it is thoroughly validated (100+ studies) and highly predictive. Epigenetic clocks account for a wide range of aging factors, including genetic, environmental, and lifestyle influences. They can be applied to various tissue types, making them versatile tools for assessing biological age. In addition, they have been shown to predict age-related diseases, longevity, and overall health more accurately than chronological age.
• Other biological age predictors may prove to be useful, but would require further independent validation.

Different Epigenetic Clocks

The concept of the epigenetic clock is based on the observation that certain DNA methylation sites on the genome change predictably with age. A good visual explanation of chronological versus methylation age is shown below (1 ):

Researchers have developed numerous epigenetic clocks that can predict biological age with a high degree of accuracy by measuring the methylation state of specific sites in the DNA. The most widely recognised epigenetic clocks include:

• Horvath's Clock (8 ): One of the first and most widely used, it applies to all human tissues and cell types tested so far.
• Hannum's Clock (9 ): Developed using blood samples and closely associated with biomarkers of aging and predictors of mortality.
• PhenoAge (5 ) and GrimAge (10 ): More recent developments that incorporate clinical biomarkers with epigenetic data, aiming to predict lifespan, healthspan, and susceptibility to specific diseases more accurately.

I hope you enjoyed the topic of biological age. I wanted to shed some light in a way that's both interesting and maybe a bit eye-opening. I'm looking forward to sharing more personal stories and scientific insights on longevity in two weeks!