Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction.

Aging is a complex physiological process that poses considerable conundrums to rapidly aging societies. For example, the risk of dying from cardio- vascular diseases and/or cancer steadily declines for people after their 60s, and other causes of death pre- dominate for seniors older than 80 years of age. Thus, physiological aging presents numerous unanswered questions, particularly with regard to changing metabol- ic patterns. Urine proteomics analysis is becoming a non-invasive and reproducible diagnostic method. We investigated the urine proteomes in healthy elderly peo- ple to determine which metabolic processes were weak- ened or strengthened in aging humans. Urine samples from 37 healthy volunteers aged 19-90 years (19 men, 18 women) were analyzed for protein expression by liquid chromatography-tandem mass spectrometry. This generated a list of 19 proteins that were differen- tially expressed in different age groups (young, interme- diate, and old age). In particular, the oldest group showed protein changes reflective of altered extracellu- lar matrix turnover and declining immune function, in which changes corresponded to reported changes in cardiovascular tissue remodeling and immune disorders in the elderly. Thus, urinary proteome changes in the elderly appear to reflect the physiological processes of aging and are particularly clearly represented in the circulatory and immune systems. Detailed identification of "protein trails" creates a more global picture of met- abolic changes that occur in the elderly.