A 2-year calorie restriction intervention reduces glycomic biological age biomarkers.

Autor:	Pribić T; Genos Ltd, Glycoscience Research Laboratory, Zagreb, Croatia., Das JK; Longitudinal Studies Section, Translation Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA., Đerek L; Clinical Department for Laboratory Diagnostics, University Hospital Dubrava, Croatia., Belsky DW; Robert N Butler Columbia Aging Center and Department of Epidemiology, Columbia University Mailman School of Public Health, New York, USA., Orenduff M; Duke Molecular Physiology Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA., Huffman KM; Duke Molecular Physiology Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA., Kraus WE; Duke Molecular Physiology Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA., Deriš H; Genos Ltd, Glycoscience Research Laboratory, Zagreb, Croatia., Šimunović J; Genos Ltd, Glycoscience Research Laboratory, Zagreb, Croatia., Štambuk T; Genos Ltd, Glycoscience Research Laboratory, Zagreb, Croatia., Hodžić AF; Genos Ltd, Glycoscience Research Laboratory, Zagreb, Croatia., Kraus VB; Duke Molecular Physiology Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA., Das SK; Jean Mayer, USDA, Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA., Racette SB; College of Health Solutions, Arizona State University, Phoenix, Arizona, USA., Banskota N; Computational Biology and Genomics Core, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA., Ferruci L; Longitudinal Studies Section, Translation Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA., Pieper C; Division of Biostatistics, Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA., Lewis NE; Departments of Pediatrics and Bioengineering, University of California, San Diego, California, USA., Lauc G; Genos Ltd, Glycoscience Research Laboratory, Zagreb, Croatia.; Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia., Krishnan S; School of Nutritional Sciences and Wellness, BIO5, University of Arizona, Tucson, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Dec 05. Date of Electronic Publication: 2024 Dec 05.
DOI:	10.1101/2024.12.04.24318451
Abstrakt:	Background/objective: In a subset of participants from the CALERIE ™ Phase 2 study we evaluated the effects of 2y of ~25% Calorie Restriction (CR) diet on IgG N-glycosylation (GlycAge), plasma and complement C3 N-glycome as markers of aging and inflammaging. Methods: Plasma samples from 26 participants in the CR group who completed the CALERIE2 trial and were deemed adherent to the intervention (~>10 % CR at 12 mo) were obtained from the NIA AgingResearchBiobank. Glycomic investigations using UPLC or LC-MS analyses were conducted on samples from baseline (BL), mid-intervention (12 mo) and post-intervention (24 mo), and changes resulting from the 2y CR intervention were examined. In addition, anthropometric, clinical, metabolic, DNA methylation (epigenetic) and skeletal muscle transcriptomic data were analyzed to identify aging-related changes that occurred in tandem with the N-glycome changes. Results: Following the 2y CR intervention, IgG galactosylation was higher at 24mo compared to BL (p = 0.051), digalactosylation and GlycAge (the IgG-based surrogate for biological age) were not different between BL and 12mo or BL and 24mo, but increased between 12mo and 24mo (p = 0.016, 0.027 respectively). GlycAge was also positively associated with TNF-α and ICAM-1 (p=0.030, p=0.017 respectively). Plasma highly branched glycans were decreased by the 2y intervention (BL vs 24 mo: p=0.013), but both plasma and IgG bisecting GlcNAcs were increased (BL vs 24mo: p<0.001, p = 0.01 respectively). Furthermore, total complement C3 protein concentrations were reduced (BL vs 24mo: p <0.001), as were Man9 glycoforms (BL vs 24mo: p<0.001), and Man10 (which is glucosylated) C3 glycoforms (BL vs 24mo: p = 0.046). Conclusions: 24-mos of CR was associated with several favorable, anti-aging, anti-inflammatory changes in the glycome: increased galactosylation, reduced branching glycans, and reduced GlycAge. These promising CR effects were accompanied by an increase in bisecting GlcNAc, a known pro-inflammatory biomarker. These intriguing findings linking CR, clinical, and glycomic changes may be anti-aging and inflammatory, and merit additional investigation.
Databáze:	MEDLINE
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