4.4 Article

Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components

Journal

GEROSCIENCE
Volume 44, Issue 1, Pages 371-388

Publisher

SPRINGER
DOI: 10.1007/s11357-021-00468-1

Keywords

Cortical microvessels; Proteomics; Brain aging; ROS scavengers; mRNA; protein stability; Glycolytic; mitochondrial proteins

Funding

  1. NIH [HL-148836, AG-063345]
  2. Louisiana Board of Regents Endowed Chairs for Eminent Scholars program [NS094834, AG074489, NS114286, AG047296]

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The study found that the differentially expressed proteins in the cortical microvessels of aged mice showed significant changes with aging, particularly in oxidative stress response, mRNA/protein stability, basement membrane composition, glycolysis, and mitochondrial function. This suggests that increased oxidative stress during aging leads to adverse changes in protein profile of brain cortical microvessels, affecting mRNA/protein stability, basement membrane integrity, and ATP synthesis capacity.
Differentially expressed (DE) proteins in the cortical microvessels (MVs) of young, middle-aged, and old male and female mice were evaluated using discovery-based proteomics analysis (> 4,200 quantified proteins/group). Most DE proteins (> 90%) showed no significant differences between the sexes; however, some significant DE proteins showing sexual differences in MVs decreased from young (8.3%), to middle-aged (3.7%), to old (0.5%) mice. Therefore, we combined male and female data for age-dependent comparisons but noted sex differences for examination. Key proteins involved in the oxidative stress response, mRNA or protein stability, basement membrane (BM) composition, aerobic glycolysis, and mitochondrial function were significantly altered with aging. Relative abundance of superoxide dismutase-1/-2, catalase and thioredoxin were reduced with aging. Proteins participating in either mRNA degradation or pre-mRNA splicing were significantly increased in old mice MVs, whereas protein stabilizing proteins decreased. Glycolytic proteins were not affected in middle age, but the relative abundance of these proteins decreased in MVs of old mice. Although most of the 41 examined proteins composing mitochondrial complexes I-V were reduced in old mice, six of these proteins showed a significant reduction in middle-aged mice, but the relative abundance increased in fourteen proteins. Nidogen, collagen, and laminin family members as well as perlecan showed differing patterns during aging, indicating BM reorganization starting in middle age. We suggest that increased oxidative stress during aging leads to adverse protein profile changes of brain cortical MVs that affect mRNA/protein stability, BM integrity, and ATP synthesis capacity.

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