A study 1 of how dietary advanced glycation end-products (AGEs) effect the structure and function of intervertebral discs (IVDs) in male and female mice concluded that high dietary AGEs impaired IVD collagen quality, altered annulus fibrosus (AF) organization and changed the biomechanical properties of female IVDs, while having no clinically-significant effect on male mice subjects. The results of the study suggest the importance of targeting AGEs in spinal health assessments and treatments of female patients—particularly those at risk for, or suffering from, Diabetes Mellitus (DM).
What’s at Stake?
Structural disruption and chronic inflammation of the IVD is one of the leading causes of back pain, disability, and lost work wages worldwide. The many contributors to IVD damage and degeneration include DM and obesity, conditions that are increasing rapidly across the globe. Obesity increases the risk of IVD herniation, spinal stenosis, chronic inflammation, and other complications of the spine. It is also associated with an increased risk of cardiovascular disease, stroke mortality, and heart attacks–particularly in women. Since AGE accumulation is known to cause complications in populations with DM, this study investigates the effects of a high AGE diet on the IVD and how sex-differences may play a role in sex-specific IVD changes and disruption.
The subjects of the study were 21 male and 23 female recently-weaned mice, separated by sex and assigned to two groups. One group received a low-AGE diet (chow), and another group was fed only high AGE chow, which had been subjected to high-temperature heating. Each subject represented a third-generation off-spring of maternal mice fed only the respective diet used in the study groups, to exclude any effects of maternal AGES on the newly-weaned experiment mice.
The high AGE chow was representative of the typical Western human diet, with 80 percent higher AGE values than those of the low AGE chow. An increased AGE content is typically caused by thermally processing (extreme heating) the foods prior to ingesting. Examples of this include microwaving or deep-frying foods.
The feeding study lasted for 6 months, after which time the mice were sacrificed, dissected, and prepared for biomechanical IVD testing through Western blot analysis. Fasting glucose and total serum AGE levels were measured and quantified, and proteins were extracted, buffered, and sonicated. A single freeze-thaw cycle was used prior to biomechanical testing to avoid the process influencing the IVD mechanics. Axial compression-tension and torsional tests were performed on caudal motion segments, and the IVD diameter measurements were taken using a caliper. Assessments of IVD morphology, collagen molecular properties, and fiber orientation were created, measured, compared, and analyzed.
The Western blot data showed a significant accumulation of AGEs accumulation of the IVD problems of the female mice fed the high AGE (H-AGE) diet compared to those fed the low AGE (L-AGE) diet. There were no changes in the IVD AGE levels or serum samples of the male mice in either feeding group. The results indicate that even without the presence of DM or obesity, dietary AGEs are likely to systemically accumulate in the IVDs of female mice—but not in males.
Further, the H-AGE female mice IVDs showed increase stiffness and torque-range, while the date on the L-AGE female mice showed no such correlation, and the male mice IVDs of both feeding groups were unaffected. This indicates that motion segment behaviors of female mouse IVDs—but not male mouse IVDs— are negatively affected by the H-AGE diet.
In addition, the AF organization and collagen fibers of H-AGE diet female mouse IVDs—but not male mouse IVDs— appeared compromised, particularly in the anterior AF. The H-AGE diet also appears to have contributed substantially to AGE accumulation and collagen damage in the AF of the female mice subjects but not the male mice subjects.
The results of this study, combined with previous study literature, suggests that female mice are negatively affected by a H-AGE diet, which appears to increase glycation within the AF collagen matrix and damage collagen and molecules in the IVD. High IVD crosslinking and collagen damage can contribute to biomechanical changes in the IVD and disrupt form and function in the unit. It appears that high AGE diets may increase these risks in female spinal tissues. Future research is needed to investigate ways to promote spinal health through dietary interventions to lower AGE levels, particularly in at-risk populations. This includes patients suffering from obesity and DM, especially females.