Blinded by their paradigm?

This 2022 human study investigated another type of aging clock:

“The glycan clock of age, based entirely on immunoglobulin G (IgG) N-glycans, can predict biological age with high accuracy. Unlike DNA methylation, glycosylation of IgG does not predict chronological age with high accuracy.

Heritability analysis of plasma glycans revealed that the majority of traits have high heritability estimates, indicating a tight genetic control of glycosylation. To better understand genetic and environmental factors influencing glycan clock variation, we performed a heritability analysis on data from two cohorts included in the TwinsUK registry.

Glycosylation is a series of enzymatic reactions in which carbohydrates are attached to other molecules (e.g., proteins or lipids) resulting in formation of complex carbohydrates and glycoconjugates commonly referred to as ‘glycans.’ Glycosylation of IgG antibody is especially interesting as it dramatically affects its function, and acts as a molecular switch between pro- and anti-inflammatory immune responses.

Heritability of the glycan clock was estimated to decompose observed phenotypic variance into three latent sources of variation:

  • A—additive genetic variance [red] represents cumulative impact of genes;
  • C—shared/common environment variance [purple] results from influences to which both members of a twin pair are exposed; and
  • E—unique environment variance [green] is events occurring to one twin but not the other, and includes measurement error.


Despite tight genetic control of the IgG glycome:

  • Heritability analysis of the glycan clock revealed only a moderate genetic contribution averaging around 39% [A, left side].
  • Including age of the individuals as a covariate in heritability analysis averaged 71% heritability estimates [B, right side].
  • Mean time difference was 7.5 years for points 1 and 2, and 6 years for points 2 and 3.

Observed increase in the genetic component could be a consequence of chronological age as a shared environmental variance characteristic for every individual and determined by their genetic makeup and epigenetic regulation.” “Heritability of the glycan clock of biological age”

Although A rejuvenation therapy and sulforaphane was cited, these researchers missed its central premise: Pro-aging epigenetic programming is directional and not purely random. Contrasting their above graphic’s heritability estimates of 39% with the age-regressed, right side’s average 71% could hardly have been more clear in illustrating this fact.

This study instead stated “Aging in general leads to epigenetic mediated deregulation of genes.” This weak sauce accompanied speculations such as “supports the notion that the glycan clock can be rejuvenated by simple lifestyle choices.”

Researchers almost always want to claim being first in finding x, y, or z. These researchers could have done that in this glycan clock study by highlighting an outstanding finding. So what happened?

An alternate explanation to their paradigm blinding them could be sponsor expectations, peer pressures, etc. I’ll ask them about it, and will update here with their response.



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