Age-dependent albumin post-translational modification landscape reveals a critical midlife transition window.

Abstract

Albumin, the most abundant plasma protein, maintains osmotic pressure, transporting diverse substances, and provides antioxidant defense. To screen aging-related proteins, we performed quantitative proteomics on plasma from 133 healthy individuals and constructed an aging-clock model. Albumin was identified as the top-ranked protein showing strong age-dependent downregulation. Since post-translational modifications (PTMs) regulate albumin function, we further investigated how its PTM landscape changes with age. Using tandem mass spectrometry, we quantitatively profiled key albumin PTMs across different age groups, focusing on the redox state of Cys34, oxidation of methionine residues, the C-terminal cleavage product, and lysine glycation. We found that the reduced form of Cys34 decreased progressively, whereas methionine oxidation at Met123, Met298, Met446, and Met548 increased sharply after 60 years of age. In parallel, lysine glycation exhibited site-specific and heterogeneous age-related patterns, while albumin C-terminal integrity increased with aging. Together, these findings suggest that a drastic change occurs in albumin PTMome between 50 and 60 years of age. This study provides a comprehensive profile of albumin PTM dynamics during aging and highlights a key midlife window in protein modification remodeling, offering potential biomarkers for monitoring aging and related physiological changes.

Abstract as supplied by the indexing source. © the authors / publisher.