Grubina, Rozalina

Altered protein homeostasis may explain the increased risk of degenerative and cardiometabolic disorders with aging. Here, we investigated the impact of chronological age and obesity on the accumulation (ratio of old to de novo synthesized proteins) of haptoglobin, fibrinogen, and apolipoprotein A‐1 (ApoA‐1) in 7 each of elderly lean (69.8 ± 5.0 years, 23.2 ± 1.8 kg/m 2 ), elderly obese (72.6 ± 5.6 years, 30.6 ± 2.3 kg/m 2 ), young lean (23.1 ± 3.2 years, 23.4 ± 1.9 kg/m 2 ), and young obese (25.2 ± 2.4 years, 30.6 ± 2.4 kg/m 2 ). Proteins were labeled with [ 13 C 6 ]‐phenylalanine, separated by 2‐dimentional gel electrophoresis, and identified by mass spectrometry. Insulin sensitivity was lower in the obese groups, while percent body fat was higher, and lean mass was lower, in the elderly. Haptoglobin accumulation was greater in the obese compared to lean (0.512 ± 0.229 vs. 0.272 ± 0.114; p = 0.008) across all ages, with no age effect. Fibrinogen trended toward higher accumulation in the obese compared to lean, with no age effect, but did not reach statistical significance (1.263 ± 2.108 vs. 0.598 ± 0.197; p = 0.094). ApoA‐1 accumulation showed no obesity or age variation. Associations remained unchanged when controlled for gender, age, and BMI. Thus, adiposity, and not chronological age, promotes protein accumulation, potentially contributing to degenerative and cardiometabolic disease risk. Supported by NIH grant RO1‐AG09531.