Reviewing Glycosylation Biomarkers of Aging and Age-Related Disease

Researchers here discuss the ongoing development of biomarkers of aging and age-related disease based on glycosylation of proteins, the attachment of a glycan to a protein. Various forms of post-translational modification occur to proteins throughout the body, changing their function, and are, to varying degrees on a case-by-case basis, necessary, tolerated, problematic, and targeted for removal by cell maintenance processes. These processes shift in response to the metabolic changes of aging, and at least some of them may useful as metrics of age-related degeneration and risk of age-related disease. At least one company, GlycanAge, works in this space, and there will likely be other similar efforts in the future.

Protein glycosylation is the biochemical process for which a carbohydrate molecule is covalently attached to a protein functional group. In biology, glycosylation mainly refers to the enzymatic process that binds glycans to proteins, affecting intracellular processes like folding and transport, and playing an important role in many cellular signaling and communication events.

Three major n-glycan structures present in human blood glycoproteins (serum, plasma, and immunoglobulins fraction) have shown clear changes with ageing. Agalactosyl n-linked oligosaccharides (NG0A2F and NG0A2FB) increase with age whereas core-fucosylated biantennary n-glycans (NA2F) decrease with age. A similar trend was observed in a study which aimed to evaluate the effects of the age and gender on the human serum n-glycans profiles: NGA2F and NGA2FB increased gradually with ageing whereas NA2F decreased. Additionally, before the age of 50 years these three glycans changed only slightly with age, but the difference between age groups 41-50 and 51-60 years was statistically significant, indicating that the age-related physiological changes occurred in the fifties.

An ageing biomarker named GlycoAgeTest has been developed, which could possibly forecast disease progression during ageing. This marker is the log of the ratio of two glycans (NGA2F and NA2F), which remains steady up to the age of 40 years and thereafter gradually increases to reach its highest level in nonagenarians. Furthermore, patients with dementia or Cockayne syndrome have shown to have a higher GlycoAgeTest level than age-matched healthy individuals. It was concluded that the value of GlycoAgeTest is better than chronological age for estimating the physiological age of a human individual, and that it could be used as an ageing biomarker for healthy humans.

Glycome analysis is emerging as a source of potential biomarkers in different pathological states. Its analysis is not easy, as the diverse structures of glycans are complex and heterogenic. Moreover, there is a wide range of possible monosaccharide combinations and linkages, that result in structurally complex glycans, which can be attached to proteins, conforming glycosylation post-translational modifications. In clinical studies, the comparison of glycans levels altered in specific diseases often leads to inconsistent results, which cannot be explained completely by the different statistical methods. This may be due to the diversity of the glycome in different populations and even in different environments. Furthermore, the use of a wide range of glycomic methodologies leads to low comparability between studies which hinders the production of clear results.



Red blood cells have an irreplaceable function to deliver oxygen to maintain bioenergetics of every single cell within our body. However, their function in age-related cognition and hearing function remains largely unknown. Our findings reveal that the red blood cell ADORA2B signaling cascade combats early onset of age-related decline in cognition, memory and hearing by promoting oxygen delivery in mice and immediately highlight multiple new rejuvenating targets".

Posted by: Robert Read at June 17th, 2021 2:07 PM

Has anyone tried out this aging test? From a brief read around it appeared to me to be a rather unstable biomarker...

Posted by: Mark at June 18th, 2021 5:56 AM

I have used their service once so far so I can't talk about its variability over time. However the results came back in line with other assessments. Fwiw I have spent the last 3 years on a consistent regime of supplements and a mostly Japanese/Meditarranean diet + exercise, Sauna and good sleep.

Measured minus Chronological (years):
GycanAge -15y
Epigenetic -14y
Levine Phenotype (blood markers) -13y
Aging.AI (blood markers) -14y

Posted by: Chris C at June 19th, 2021 2:50 AM

@Chris C. Interesting. If you don't mind me asking what's your supplement regime?

Posted by: Kel at June 20th, 2021 6:24 PM

@ Chris C: glad to see it is consistent with measures of methylation and also blood proxies. Would you mind sharing your chronological age? thanks, M

Posted by: Mark at June 21st, 2021 6:33 AM

@Kel, @Mark.
Sure, I'm about to turn 50.
Supplements I take regularly are:
- NAD precursors (Nuchido Time+)
- Vit D3/K1/K2
- IP6
- Creatine
- Cocoa polyphenols
- Berberine (not same days as AKG)
- Curcumin
- Omega3: EPA/DHA
- Sulforaphane
Periodically I will switch things out and cycle in Astaxanthin or Spermidine.
Otherwise diet, exercise, sauna and sleep!

Posted by: Chris C at June 21st, 2021 6:53 AM

Hi @Chris C . What is IP6? And how much AKG do you take? Is it a one time dose. Thanks in advance.

Posted by: Chuck Frasher at July 25th, 2021 10:16 PM
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