A Biomarker of Aging Based on Protein Glycosylation Patterns

Today I'll note the development of a commercial aging clock based on glycosylation patterns of immunoglobulin G, a marker for the inflammatory status of the immune system, by startup biotech company GlycanAge. There are at present any number of approaches to measuring biological age, the burden of cell and tissue damage that leads to dysfunction. Stage of development varies widely, with the most work to date being on clocks based on changes in DNA methylation. There are also clocks that use protein levels in blood, weighted combinations of simple measures such as grip strength, and other approaches besides these. The important goal in these efforts is to produce a measure that can quickly be applied before and after a potential intervention to quantify the degree to which it reverses aging. A generally accepted, fast, cheap measure of age would greatly accelerate development of rejuvenation therapies, and might finally focus more research attention on repair-based interventions that have a greater chance of producing large effect sizes.

That still lies a way in the future, however. The challenge with near all of these clocks is that they are constructed by comparing data that is far downstream of the causes of aging against outcomes such as mortality risk. Thus there is no good understanding of what exactly it is that these biomarkers of aging are actually measuring, under the hood. The glycosylation clock is more clear than most, in that it is very directly an assessment of the chronic inflammation of aging, but even then it is a challenge to say which underlying causes of aging are more or less important in that outcome. The situation is much murkier for other clocks.

This lack of knowledge means that a clock must be calibrated against each potential intervention, in the slow, hard way, by waiting to assess lifespan, in order to ensure that it is a valid test. This somewhat defeats the point of the exercise, to make development faster for new interventions. Further, it means that most of the commercially available tests are not actionable: the test will produce a number, but that number says nothing about what might be done to change it. The glycosylation clock is at least ahead of the game on that front, pointing directly to whatever approaches are known to reduce chronic inflammation, but this may or may not still be somewhat disconnected from other processes of aging.

Start-up claims first commercial glycan-based age test

GlycanAge is a British-Croatian start-up focused on analysing glycosylation patterns to deliver what it claims is the "most accurate" measure of biological age. Glycans are complex sugars that contribute significantly to the structure and function of the majority of proteins. Changes in glycans have been reported in many inflammatory diseases, where they reflect disease activity, or in some cases even precede the development of disease.

The company, leveraging patents from leading glycomics research lab Genos, has developed a direct-to-consumer glycan test kit that measures biological age and chronic low grade systemic inflammation. When the company first started in 2016, it worked using plasma samples, which was expensive and hard to scale commercially, but it has since developed a dry blood spot based test that delivers the same results.

"Telomeres are DNA timers that limit the lifespan of a single cell. On the individual cell level, telomeres are the best marker of aging. However, we are composed of trillions of cells and each of them has different age and expected lifespan. GlycanAge is different because it measures your immunoglobulin G glycosylation, which directly correlates with the level of inflammation in your body. It will give you information about the immune balance of your organism that changes with age, health and life circumstances."

GlycanAge

GlycanAge is a science-based test that will accurately determine your biological age. This is a first commercial glycan-based test that will put a single number to your health. Glycans are complex sugar molecules (carbohydrates), and one of the four main building blocks of life. They are involved in almost every process in our body.

More than half of all our proteins are glycosylated, with their glycan parts often playing an essential functional role. Glycans are crucial for the functioning of our immune system. Glycans attached to the antibodies modulate their activity and determine if they will have a pro-inflammatory or anti-inflammatory function. Thus, it is not surprising that glycan profiles can serve as a measure of an individual's health. The GlycanAge test looks at the glycosylation pattern of the immunoglobulin G (IgG) molecule. IgG is the most prevalent antibody type in our blood and especially important in controlling inflammation and pathogens.

Immunoglobulin G (IgG), the most prevalent antibody type in our blood, is always glycosylated - meaning it has glycans attached to it. The type of the glycan group attached to the IgG determines if IgG will enhance or reduce inflammation. Since inflammation can exhaust our resources to keep the body in good health, low level of inflammation was shown to be a predictor of successful ageing. Therefore, IgG glycosylation is also a good measure of biological age.

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