Milk fat globule membrane supplementation with voluntary running exercise attenuates age-related motor dysfunction by suppressing neuromuscular junction abnormalities in mice

Abstract

Age-related loss of skeletal muscle mass and function attenuates physical performance, and maintaining fine muscle innervation is known to play an important role in its prevention. We had previously shown that consumption of milk fat globule membrane (MFGM) with habitual exercise improves the muscle mass and motor function in humans and mice. Improvement of neuromuscular junction (NMJ) was suggested as one of the mechanisms underlying these effects. In this study, we evaluated the effect of MFGM intake combined with voluntary running (MFGM-VR) on morphological changes of NMJ and motor function in aging mice. Seven months following the intervention, the MFGM-VR group showed a significantly improved motor coordination in the rotarod test and muscle force in the grip strength test compared with the control group at 13 and 14months of age, respectively. In 14-month old control mice, the extensor digitorum longus muscle showed increased abnormal NMJs, such as fragmentation and denervation, compared with 6-month old young mice. However, such age-related deteriorations of NMJs were significantly suppressed in the MFGM-VR group. Increase in the expression of NMJ formation-related genes, such as agrin and LDL Receptor Related Protein 4 (LRP4), might contribute to this beneficial effect. Rotarod performance and grip strength showed significant negative correlation with the status of denervation and fragmentation of NMJs. These results suggest that MFGM intake with voluntary running exercise effectively suppresses age-related morphological deterioration of NMJ, thus contributing to improvement of motor function.

Continuous Supplementation of Milk Fat Globule Membrane with Habitual Exercise from a Young Age Improves Motor Coordination and Skeletal Muscle Function in Aged Mice

“…Second, dietary MFGM supplementation combined with VR attenuated aging-associated loss of muscle mass and strength in naturally aging mice, consistent with our previous findings in SAM mice (25). MFGM intake or VR alone did not significantly improve muscle mass and strength, which is in agreement with previous studies (29,(35)(36)(37). These results suggest that improvements in muscle characteristics that are associated with MFGM ingestion and VR depend on the synergism between these factors.…”

“…Considering the drastic decrease of time spent on the rotarod, in the present study, 20-to 21-mo-old mice were in the later phase of aging. On the other hand, severe NMJ abnormalities were rarely observed in the muscles of 14-moold mice in our previous study (29); therefore, mice of this age may be during the early phase of aging. In this study, we observed that the age-related reduction in Dok-7 levels in muscle was rescued by MFGM intake with VR in 21-mo-old mice.…”

“…Justice et al (28) also demonstrated that the rate at which motor coordination declines among mice aged 20-26 mo was equivalent to that among humans aged 70-89 y. Our recent study demonstrated that MFGM intake combined with voluntary exercise ameliorated age-related deterioration in motor coordination and muscle strength of naturally aging mice during the early phase of aging (at 14 mo of age) (29). However, the effect of MFGM intake plus exercise on much older mice has not been clarified.…”

“…In our previous study (29), we showed that continuous intake of MFGM combined with VR diminished ageassociated reductions in motor coordination and muscle strength in 14-mo-old mice, which was associated with increased expression of muscle-derived agrin. The present study revealed that MFGM with VR also improved motor coordination and muscle force in 20-and 21-moold mice, respectively, through increased expression of Dok-7.…”

Milk-Fat Globule Membrane Plus Glucosamine Improves Joint Function and Physical Performance: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study

“…Thus far, there are no reports of glucosamine improving the active range of motion at any joint. However, there are reports of MFGM combined with light exercise improving muscle strength in both mice and humans (2)(3)(4)8) and improving motor coordination via the neuromuscular junction (20). The sphingomyelin contained in MFGM is thought to play a role in these effects (8).…”