Different patterns in age-related morphometric alteration of myelinated fibers and capillaries of the tibial nerve: a longitudinal study in normal rats.

Age-related regression of myelinated fibers in peripheral nerves of the lower limbs is strongly influenced by capillaries and results in balance dysfunction and falls. However, the temporal relationships between alteration patterns of myelinated fibers and capillaries have not yet been clarified. This study aimed to investigate age-related morphological and histological changes of both myelinated fibers and capillaries in peripheral nerves to clarify whether myelinated fibers or capillaries change earlier. Seven male Wistar rats each were randomly selected at 20 weeks (young group), 70 weeks (middle group), and 97 weeks (old group) for histological evaluations. The left and right tibial nerves were removed morphologically and histologically to examine myelinated fibers and capillaries. Axon diameter and myelin thickness were almost unaltered in the middle group compared with the young group but were significantly reduced in the old group when compared with the other two groups. However, the capillary diameter and number of microvascular branch points were substantially reduced in the middle group. The current study demonstrates that myelinated fibers of peripheral nerves show signs of regression in elderly rats, whereas capillaries start to reduce in middle-aged animals. In normal aging of the tibial nerve, capillaries may regress before myelinated fibers.

Endurance exercise increases the protein levels of PGC-1α and respiratory chain complexes in mouse skeletal muscle during atorvastatin administration.

Statins and exercise reduce cardiovascular disease incidence. We investigated whether endurance exercise in mice induces mitochondrial adaptation in skeletal muscle and muscle injury during administration of atorvastatin, a member of the statin medication class. Male C57BL mice were assigned to one of three groups: control (Con), statin (Statin), or statin and exercise (Statin + Ex). Atorvastatin was administered, and exercise performed on a treadmill for 8 weeks. The levels of mitochondria-associated proteins, PGC-1α, and respiratory chain complex, (COX) I-V, in the quadriceps femoris, and serum creatine kinase, a muscle injury marker, were measured. PGC-1α and COX I-V were upregulated in the Statin + Ex group compared to those in the Statin and Con groups; serum creatine kinase levels were similar. Endurance training in mice induced mitochondrial adaptation in skeletal muscle without causing muscle injury, during atorvastatin administration.

Remodeling of myelinated fibers and internal capillaries in distal peripheral nerves following aerobic exercise in aged rats.

The aim of this study was to determine whether aerobic exercise (AE) in old age contributes to improving the morphologies of myelinated fibers (MFs) in peripheral nerves as well as capillaries. Furthermore, we investigated whether such processes are associated with complementary activity of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the circulating blood and peripheral nerve tissue. Fourteen male Wistar rats (age: 95 wk) were randomly divided into moderate AE ( n = 8) and sedentary (SED; n = 6) groups. Rats in the AE group performed treadmill running for 1 h per day for 2 wk, following which the bilateral tibial nerves of the two groups were removed to examine MF and capillary structure. Levels of BDNF and VEGF in the serum and peripheral nerves were analyzed via enzyme-linked immunosorbent assay. Myelin thickness, axon diameter, and capillary luminal diameter were significantly larger in the AE group than in the SED group ( P < 0.0001). Levels of serum BDNF and VEGF were significantly lower and higher, respectively, in the AE group than in the SED group ( P < 0.001). Conversely, BDNF and VEGF levels in tibial nerve tissue were significantly higher, respectively, and lower in the AE group than in the SED group ( P < 0.001). In conclusion, our study indicates that regular AE induces enlargement of the capillaries and thickens the myelin in aged peripheral nerves, likely via a complementary process involving BDNF and VEGF. NEW & NOTEWORTHY Accumulating evidence indicates that age-related sarcopenia is accompanied by the degeneration of myelinated fibers (MFs) in peripheral nerves. Our study indicates that regular aerobic exercise contributes to increased thickness of the myelin surrounding MFs and enlargement of the capillaries, likely via a complementary process involving brain-derived neurotrophic factor and vascular endothelial growth factor. Our findings demonstrate that regular, moderate-intensity aerobic exercise may help to prevent and reverse peripheral nerve regression in older adults.

Age-related morphological regression of myelinated fibers and capillary architecture of distal peripheral nerves in rats.

BACKGROUND: Regression of myelinated peripheral nerve fibers in the lower extremities contributes to sarcopenia and balance dysfunction in normal aging. This subclinical regression of myelinated fibers (MFs) is heavily influenced by alterations in microvasculature, though the mechanism underlying these age-related degenerative phenomena remains unclear. The aim of the present study was to examine age-related regressions in myelinated distal peripheral nerve fibers as well as capillary architecture in rats using both morphological and histochemical methods. RESULTS: MFs were categorized into tertiles of 'large', 'medium', and 'small' sizes based on the distribution of MF diameters. A two-way ANOVA was used to assess effects of fiber size (large/medium/small) and group (young/elderly) on myelin thickness, axon diameter, myelin perimeter, axon perimeter, and G-ratio (axon diameter/fiber diameter). Significant main effects were observed for both MF size and group with respect to all dimensions except for G-ratio. Values for fiber diameter (P < 0.01), myelin thickness (P < 0.01), axon diameter (P < 0.01), myelin perimeter (P < 0.01), and axon perimeter (P < 0.01) were significantly lower than those in the young group. Additionally, mean capillary diameter and number of microvascular branch points were significantly lower in the elderly group than in the young group. CONCLUSIONS: The present study demonstrated that spontaneous age-related regression predominantly occurs for all fiber sizes in the distal peripheral nerves and the capillary architecture. The results of the present study further suggest that both the distal MFs and capillaries in the peripheral nerve may simultaneously regress with aging.

[Prevention programs of risk factors for falls].

Approximately 17% of Japanese older people fall for a year. The femoral neck fractures with falls caused by various functional problems make them depress remarkably activities of daily living and quality of life. In risk factors for falls in old people, muscle weakness, balance and gait disorders particularly increases to falls. The major results from recent systematic reviews have indicated that interventions of exercise, multifactorial, environmental modification and gradual withdrawal of psychotropic medication in community-dwelling elderly people were effective for preventing falls. Regarding the older people in hospitals and sanatoriums, it appeared that comprehensive multifactorial interventions and vitamin D supplementation could be effective in falls rather than exercises intervention only. However, the short period of the exercise intervention may affect ineffectiveness in preventing falls.

The Morphological Changes in the Capillary Architecture of the Tibial Nerve Associated with Spontaneous Aging and Aerobic Exercise Intervention during Aging in Rats.

[Purpose] Peripheral nerve degradation associated with aging is linked to failure of interactions in capillary metabolism. The aim of this study was to morphologically investigate the age-related changes in the capillary architecture of the tibial nerve in spontaneous aging and with aerobic exercise intervention in rats. [Subjects] Male Sprague-Dawley rats (n=15) were used in the present study. [Methods] The rats were divided into control (Cont, n=5), elderly (Elder, n=5), and elderly with aerobic exercise (Elder+Ex, n=5) groups. Aerobic training of low intensity was performed for 10 weeks using a treadmill starting at 96 weeks of age by the Elder+Ex group. The capillary diameter, cross-sectional area and number of microvascular ramifications in the tibial nerve were compared among the Cont (20-week-old), Elder (106-week-old) and Elder+Ex groups using three-dimensional images gained from confocal laser scanning microscopy. [Results] The capillary diameter, cross-sectional area and number of microvascular ramifications in the Elder group were significantly smaller than those observed in the Cont and Elder+Ex groups. [Conclusion] These findings suggest that the capillaries in the peripheral nerve degrade with spontaneous aging and that aerobic exercise of low intensity promotes angiogenesis, and protects the capillary from oxidative stress.