Plasma biomarkers of mouse aging.

Normal aging is accompanied by a series of physiological changes such as gray hair, cataracts, reduced immunity, and increased susceptibility to disease. To identify novel biomarkers of normal aging, we analyzed plasma proteins of male mice longitudinally from 2 to 19 months of age. Plasma proteins were analyzed by two-dimensional gel electrophoresis and identified using mass spectrometry (MS), MS/MS and liquid chromatography MS/MS. We found that many plasma proteins exist as multiple isoforms with different masses and/or charges. Thirty-nine protein spots (corresponding to six distinct proteins) have been identified, 13 of which exhibited significant changes with age. For example, several proteins increased significantly during aging including one isoform of transthyretin, two isoforms of haptoglobin, and three isoforms of immunoglobulin kappa chain. Conversely, several proteins decreased significantly during aging including peroxiredoxin-2, serum amyloid protein A-1, and five isoforms of albumin. Identification of these proteins provides new biomarkers of normal aging in mice. If validated in humans, these biomarkers may facilitate therapeutic interventions to identify premature aging, delay aging, and/or improve healthspan of the elderly.