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A 2-year calorie restriction (CR) trial in healthy adults shows shifts in glycomic biomarkers of biological age, offering insight into how diet may influence molecular aging pathways.
The Discovery:
In a subset of CALERIE Phase 2 participants (n=26), CR reduced an IgG-based biological age index (GlycAge) between 12 and 24 months. Changes were also seen in plasma glycans and complement C3 glycosylation, alongside transcriptomic changes in skeletal muscle genes tied to protein folding and glycosylation.
The Science:
IgG GlycAge: Stable at 12 months, but significantly lower at 24 months, independent of body weight changes.
IgG N-glycome: Increases in total and di-galactosylation at 24 months; bisecting GlcNAc increased at 12 and 24 months.
Plasma N-glycome: Decreases in tetra-sialylated and highly branched glycans; increases in asialylated and agalactosylated glycans; bisecting GlcNAc and high-mannose glycans rose.
Complement C3: Protein levels decreased at 12 and 24 months, with reductions in pro-aging glycoforms (Man9, Man9Glc1).
Immune/metabolic associations: GlycAge positively correlated with inflammatory biomarkers TNF-α, ICAM1, TGF-β, PDGF-AB.
Muscle transcriptome: CR increased expression of HSPA5, an ER stress chaperone aiding proteostasis.
Comparison with clocks: GlycAge reduction did not track with most DNA methylation clocks, but resembled DunedinPACE slowing.
Your Action:
Do not self-impose severe CR without medical oversight, risks outweigh benefits. Instead, adopt moderate calorie control, balanced diet, and exercise, which support metabolic health and overlap with CR’s molecular benefits.
Bottom Line:
Two years of calorie restriction modestly lowered glycan-based biological age, highlighting glycans as emerging biomarkers of human aging.
Source:
A 2-year calorie restriction intervention may reduce glycomic biological age biomarkers – a pilot study. npj Aging. Pribić T, Das JK, Đerek L, Belsky DW, Orenduff M, Huffman KM, Kraus WE, Deriš H, Šimunović J, Štambuk T, Frkatović-Hodžić A, Kraus VB, Das SK, Racette SB, Banskota N, Ferrucci L, Pieper C, Lewis NE, Lauc G, Krishnan S.
https://doi.org/10.1038/s41514-025-00254-9
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Disclaimer:
This newsletter is for informational purposes only and does not substitute professional medical advice. Always consult with a healthcare provider before making any changes to your health regimen.