Epigenetic vs. Glycan Ageing Clocks: Which is Better for Measuring Biological Age?

As the never-ending quest for longevity continues, researchers are constantly delving deeper into the mysteries of the ageing process. One of the most tantalising avenues of investigation has been the development of the so-called "ageing clocks" - tools that utilise different biomarkers to estimate our biological age.

Thus far, two types of these clocks have garnered significant attention: epigenetic and glycan ageing clocks. The former is based on the idea that chemical modifications to our DNA over time can predict how we will age biologically, while the latter focuses on changes in sugar molecules on Immunoglobulin G antibodies, backing up the "inflammaging" theory and the constant increase of chronic low-grade inflammation as the main driver of ageing and diseases.

However, while both clocks show promise in predicting age-related health outcomes and potentially even longevity, there is still much to learn about the advantages and disadvantages of each, and how they can be combined to give a complete picture of ageing. 

But what exactly are epigenetic and glycan ageing clocks, and how do they differ? Also, is there a way for individuals to implement changes in their lifestyles that could make them biologically younger or are we predetermined to age in a specific way? Let's dive in and explore this fascinating field of study.

In this article, we’ll cover:

• The intricacies of epigenetic ageing

• The characteristics of glycan ageing

• Differences between epigenetic and glycan ageing

• Why GlycanAge is the best test for measuring your biological age

Introduction

The science of ageing is studying a complex web of molecular processes that occur within the human body. While most of us understand that ageing is a process of accumulating molecular flaws in the body over time, much more goes into the ageing process.

For decades, scientists have been exploring various mechanisms that affect ageing, and with the advent of modern technology, we've been able to get closer to understanding what causes us to age. One of the most promising areas of research has been in measuring biological age.

This means that a person's biological age could be different from their chronological age. 

Chronological age is defined by the date of birth and is influenced solely by the linear passage of time, year per year, every 356 days, with the same pace for all of us. However, some people stay healthier, preserving the superior functional capacity of their body over an average person of their age. They have a slower pace of ageing and biologically resemble chronologically younger people.

Recently, two different methods of biological age measurement have emerged as frontrunners - the Epigenetic Ageing Clock and the Glycan Ageing Clock.

What is Epigenetic Ageing?

Precision medicine and ageing clocks are two areas of healthcare that are becoming increasingly important in our rapidly ageing population. One of the most fascinating research areas in this field is the study of epigenetic ageing, which involves changes in gene expression that occur as we age.

So, what is epigenetic ageing, and why is it important? 

Essentially, epigenetic ageing refers to changes in the chemical tags (methyl groups) that attach to our DNA over time, leading to alterations in gene expression and potentially leading to a wide range of age-related diseases. 

Methylation patterns change as we age, and researchers have identified specific sites on the genome where methylation patterns change predictably over time and can be used to estimate a person's biological age.

Epigenetic Ageing Clocks

The most well-known epigenetic ageing clock is the Horvath clock, which was developed by Steve Horvath at the University of California, Los Angeles. The Horvath clock is based on methylation patterns at 353 CpG sites across the genome. By measuring methylation patterns at these sites, researchers can estimate a person's chronological age with high accuracy. 

In people where estimated age doesn't perfectly match their chronological age, this deviation points to something biologically meaningful and is in part related to what people call biological age. 

The Horvath clock has been used in various studies to investigate the relationship between biological age and different health outcomes. The main disadvantage of the Horvath clock is that it too accurately predicts chronological age, thus several “second generation” epigenetic clocks like PhenoAge, and GrimAge have been developed that are calibrated using different known predictors of health outcomes. 

As a lot of epigenetic clocks have been developed so far, it seems that their main advantage over the other ageing clocks would be in forensics at identifying missing people or helping doctors with patients that can’t or won’t communicate. However, although they are great at measuring chronological age, they don’t necessarily do a great job at measuring biological age. 

Recently, a new epigenetic ageing clock was developed. Tally Health is designed by a renowned professor of genetics, David Sinclair, from the Harvard Medical School. While the Horvath clock looks at the same 353CpG sites across 51 different healthy tissues and cell types, giving a "pan-tissue "biological age of a person, Tally Health looks at 850,000 CpG sites in a buccal swab. 

This makes Tally Health very practical, but at the same time, the epigenetic information on biological age is restricted only to the methylation changes in the DNA of epithelial cells from your mouth. Moreover, since Tally Health is a very recently developed test, the data about its predictive power for favourable and unfavourable health outcomes is still missing.

Since we don’t have access to their research, we can’t go into detail about what their process looks like. 

What is Glycan Ageing?

It is known that many biological and environmental factors influence ageing (just think of the blue zones), and scientists have been studying these factors trying to understand how they work. Genes are important but not crucial determinants of how fast people age or how healthy they are. Only about 40% of longevity is defined by our genes and the rest is lifestyle.

This means that the long lifespans of your parents and grandparents don’t necessarily guarantee you with just as long a lifespan as they had.

In the attempt to measure a person's actual health and biological age, one specific cellular process called glycosylation has gotten recent attention. Glycosylation is an enzymatic and highly specific attachment of complex carbohydrates – glycans –on proteins, lipids, RNA, and cellular membranes, resulting in the formation of glycoconstructs that have an essential role in immunity and cell-to-cell communication and signalling. 

One such glycoprotein is immunoglobulin G (IgG) - the most common antibody in the blood, which is known to become more pro-inflammatory over time and can lead to various age-related health issues like inflammation, cardiovascular disease, renal failure, autoimmunity, and cognitive decline. 

Glycans attached to IgG change as we age, and the glycan ageing clock is a new biomarker that measures glycans' changes in the body over time, estimating a person's immune health and biological age.

This means that by looking into glycans, we can accurately measure the changes in one’s biological age that happen because of lifestyle choices, stress and unexpected events. Just like your chronological age changes, so does your biological age, which is why it’s important to regularly re-test. 

GlycanAge – Biological Ageing Clock

Scientists have long been fascinated by ageing, and research has revealed various factors that contribute to the ageing process, including genetics, environmental exposure, and lifestyle habits. 

Recent studies have focused on a new potential tool that could help predict ageing – the glycan ageing clock – a genuinely unique clock based on the essential molecule of life, carbohydrates, or simply glycans. 

GlycanAge is the first and single ageing clock based on glycans, which was developed by our founder, Professor Gordan Lauc, at the Genos Glycoscience Laboratory, a Croatian biotech company and the world's biggest lab for high-throughput glycan analysis. 

A study on more than 5,000 individuals, published in 2013 revealed that as people age, glycans on IgG antibodies change in a predictable way but give pretty skewed estimates of chronological age. That error is biologically significant and points to health conditions related to disease risk biomarkers like high blood pressure and increased insulin, glucose, cholesterol, LDL, BMI, and HbA1c in people of higher biological age.

People who have higher biological ages than their chronological ages also show faster deterioration of health.

Large epidemiological studies revealed that glycans change more than a decade before cardiovascular events, hypertension, insulin resistance, or other health issues manifest, and they can be affected by environmental factors such as diet, stress, and exposure to toxins. 

And although glycan ageing clock tracks generalised ageing, just like DNA methylation clocks, the biggest advantage of GlycanAge is its capability to predict future hospitalisation due to the broadest range of diseases including influenza and pneumonia, circulatory diseases, diabetes, metabolic diseases, etc. 

Since glycans on IgG are important regulators of chronic inflammation, they are not only predictive biomarkers for these diseases but also functional effectors that contribute to disease development. 

This means that individuals have more power over their biological age than previously thought. With a simple change in diet, exercise routine and sleep pattern, you can significantly impact your biological age.

Scientists at Genos are committed to harnessing the power of glycans, which led them to develop a best-in-class solution packaged into a simple at-home test. GlycanAge uses only 4 dry drops of blood from the finger to generate a glycan readout of 27 different structures. 

Personal IgG glycan readout is then compared against the glycans of 100.000s of people from 20 to 80 years of age and fitted to reveal the actual biological age of a person. Results are made available on the client's dashboard. 

GlycanAge longevity specialists also provide complimentary guidance for an optimal health and wellness journey matching the client's results. Lifestyle interventions are known to be beneficial for health and have been shown to also change GlycanAge, which enables the use of GlycanAge as the personalised navigator through healthy ageing.

Differences between Epigenetic and Glycan Ageing

While epigenetic and glycan ageing clocks are both based on changes that occur as we age, there are several key differences between these two types of clocks.

⮚     One major difference is that epigenetic clocks are based on changes in DNA methylation patterns, while the glycan clock is based on changes in glycans. This means that epigenetic clocks measure information (methylation of DNA), while glycan clock measures changes at the level of functional effectors (glycans attached to immunoglobulins).

⮚     Another difference between these two types of clocks is the type of information they provide. Epigenetic clocks give information on DNA methylation, mostly of unknown functional roles, while the glycan clock provides information about cell signalling and communication. This means that epigenetic clocks may be more helpful in understanding the underlying mechanisms of ageing, while the glycan clock may be more beneficial for identifying age-related changes that contribute to disease.

⮚     A third difference between these two types of clocks is the tissues or fluids they measure. Epigenetic clocks can be measured in various tissues, including blood, saliva, and skin. On the other hand, the glycan clock is typically measured in blood or plasma samples. This means epigenetic clocks may be more helpful in studying tissue-specific changes that occur in different cells as we age, while glycan clock may provide a more systemic view of ageing and chronic inflammation at the level of the entire body.

⮚     Another difference between epigenetic and glycan ageing clocks is the level of technical expertise required to perform the measurements. Epigenetic clocks can be measured by laboratory techniques and multi-array chips predesigned for DNA methylation pattern analysis, while glycan clock requires specialised equipment, extensive laboratory techniques, and highly specific trained personnel. 

Despite these differences, both epigenetic and glycan ageing clocks have shown promise in predicting age-related health outcomes. For example, epigenetic clocks have been shown to predict mortality as increased DNA methylation age is related to the risk of disease. 

And although both glycan and epigenetic ageing clocks track generalised ageing, the biggest advantage of GlycanAge is its capability to predict future hospitalisation due to the broadest range of diseases including influenza and pneumonia, circulatory diseases, diabetes, metabolic diseases, etc.

It is important to emphasise that “epigenetic clock” is a generic name that includes several different clocks and that information given by one of the clocks cannot be extrapolated to other epigenetic clocks. 

On the other hand, the glycan ageing clock is responsive to various lifestyle and pharmacological interventions which makes it the perfect biomarker for optimising personal lifestyle habits through biohacking, as a personal navigator to health, wellness, and longevity or simply preventing future bad health outcomes related to hormonal imbalance.

Let’s see what this specifically means once we compare GlycanAge to Tally Health.

Conclusion

Epigenetic and glycan ageing clocks are two emerging fields in the study of ageing that provide essential insights into the biological processes that contribute to age-related diseases. While these two types of clocks differ in the type of information they provide, the tissues they measure, and the technical expertise required to perform the measurements, they both have shown promise in predicting age-related health outcomes. 

As research in these fields continues to evolve, epigenetic and glycan ageing clocks will likely play an increasingly important role in understanding the mechanisms of ageing and developing interventions to promote healthy ageing.