Age-related changes in perimicrovascular protein distribution

The diffusion hypothesis for physiological aging proposes that an increase in interstitial matrix fiber-to-gel ratio causes a decrease in nutrient diffusion to the cells. This hypothesis predicts a decrease in interstitial matrix protein with age. The objective was to test this hypothesis by determining age-related changes in plasma protein distribution in perimicrovascular and distal regions of rat mesentery interstitial matrix. Rats that were 77, 140, 210, 315, 455, and 630 days old were anesthetized with pentobarbital sodium, and a mesenteric loop was exteriorized. Intravital video microspectrophotometry was performed using wavelengths of 280, 320, and 700 nm. Perimicrovascular protein concentrations from the protein absorbance images were used to obtain the histogram, mean, and skewness of the proximal and distal protein concentration distributions. An exponential gradient model was also used to obtain the proximal and distal protein concentrations and gradient decay constants. Proximal protein concentration increased from 77- to 140-day-old rat and then decreased gradually through 210-, 315-, 455-, and 630-day-old rats. Distal concentration decreased gradually from 140- to 630-day-old rats. There was an increase in positive skewness of the proximal protein distributions from 140- through 630-day-old rats. We found an age-related decrease in perimicrovascular protein and propose that this is due to a decrease in protein permeability with age. The results support the diffusion theory of aging.