Heritability of the glycan clock of biological age.

Autor:	Mijakovac A; Division of Molecular Biology, Department of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia., Frkatović A; Genos Glycoscience Research Laboratory, Zagreb, Croatia., Hanić M; Genos Glycoscience Research Laboratory, Zagreb, Croatia., Ivok J; Genos Glycoscience Research Laboratory, Zagreb, Croatia., Martinić Kavur M; Genos Glycoscience Research Laboratory, Zagreb, Croatia., Pučić-Baković M; Genos Glycoscience Research Laboratory, Zagreb, Croatia., Spector T; Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom., Zoldoš V; Division of Molecular Biology, Department of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia., Mangino M; Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.; NIHR Biomedical Research Centre at Guy's and St Thoma's Foundation Trust, London, United Kingdom., Lauc G; Genos Glycoscience Research Laboratory, Zagreb, Croatia.; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 Dec 22; Vol. 10, pp. 982609. Date of Electronic Publication: 2022 Dec 22 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.982609
Abstrakt:	Immunoglobulin G is posttranslationally modified by the addition of complex N-glycans affecting its function and mediating inflammation at multiple levels. IgG glycome composition changes with age and health in a predictive pattern, presumably due to inflammaging. As a result, a novel biological aging biomarker, glycan clock of age, was developed. Glycan clock of age is the first of biological aging clocks for which multiple studies showed a possibility of clock reversal even with simple lifestyle interventions. However, none of the previous studies determined to which extent the glycan clock can be turned, and how much is fixed by genetic predisposition. To determine the contribution of genetic and environmental factors to phenotypic variation of the glycan clock, we performed heritability analysis on two TwinsUK female cohorts. IgG glycans from monozygotic and dizygotic twin pairs were analyzed by UHPLC and glycan age was calculated using the glycan clock. In order to determine additive genetic, shared, and unique environmental contributions, a classical twin design was applied. Heritability of the glycan clock was calculated for participants of one cross-sectional and one longitudinal cohort with three time points to assess the reliability of measurements. Heritability estimate for the glycan clock was 39% on average, suggesting a moderate contribution of additive genetic factors (A) to glycan clock variation. Remarkably, heritability estimates remained approximately the same in all time points of the longitudinal study, even though IgG glycome composition changed substantially. Most environmental contributions came from shared environmental factors (C), with unique environmental factors (E) having a minor role. Interestingly, heritability estimates nearly doubled, to an average of 71%, when we included age as a covariant. This intervention also inflated the estimates of unique environmental factors contributing to glycan clock variation. A complex interplay between genetic and environmental factors defines alternative IgG glycosylation during aging and, consequently, dictates the glycan clock's ticking. Apparently, environmental factors (including lifestyle choices) have a strong impact on the biological age measured with the glycan clock, which additionally clarifies why this aging clock is one of the most potent biomarkers of biological aging. Competing Interests: AF, MH, JI, MMK, MP-B, and GL are employed by the Genos Glycoscience Research Laboratory. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Mijakovac, Frkatović, Hanić, Ivok, Martinić Kavur, Pučić-Baković, Spector, Zoldoš, Mangino and Lauc.)
Databáze:	MEDLINE
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