Kenji Goto1, Kiyohito Naito2, Shinji Nakamura3, Nana Nagura1, Yoichi Sugiyama1, Hiroyuki Obata1, Ayaka Kaneko1, Kazuo Kaneko1. 1. Department of Orthopaedics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. 2. Department of Orthopaedics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: knaito@juntendo.ac.jp. 3. Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Abstract
AIMS: Senescence is the normal decline in physiological functions due to aging that results in cell dysfunction. However, age-associated changes in peripheral nerves have not been elucidated. We observed histological changes in the sciatic nerves of young and older mice to investigate how peripheral nerves changed with age, and we evaluated protective mechanisms of peripheral nerves against aging. MAIN METHODS: Sciatic nerves were collected from female C57BL/6 mice at the ages of 8 weeks (young group) and 78 weeks (aged group) and examined histologically. Using hematoxylin and eosin staining, the number and density of sciatic nerve axons were evaluated. Through immunofluorescence staining, the expression of nerve-specific proteins, oxidative stress markers, and a neuronal aging marker (REST/NRSF) were investigated, and the intensity of fluorescence was quantified. The differences between the groups were assessed, and age-associated peripheral nerve changes were evaluated. Statistical analysis was performed using the Mann-Whitney U test. KEY FINDINGS: Although the number and density of axons did not differ significantly between the groups, they were lower in the aged group than in the young group. In addition, the fluorescence intensity of each marker did not differ significantly between the groups, but the expression of REST/NRSF alone was significantly higher in the aged group than in the young group (p < 0.05). SIGNIFICANCE: This study suggested that peripheral nerve functions are preserved by the expression of REST/NRSF, which increases with age. Because oxidative stress did not change, the protective effects of REST/NRSF are considered to be related to oxidative stress.
AIMS: Senescence is the normal decline in physiological functions due to aging that results in cell dysfunction. However, age-associated changes in peripheral nerves have not been elucidated. We observed histological changes in the sciatic nerves of young and older mice to investigate how peripheral nerves changed with age, and we evaluated protective mechanisms of peripheral nerves against aging. MAIN METHODS: Sciatic nerves were collected from female C57BL/6 mice at the ages of 8 weeks (young group) and 78 weeks (aged group) and examined histologically. Using hematoxylin and eosin staining, the number and density of sciatic nerve axons were evaluated. Through immunofluorescence staining, the expression of nerve-specific proteins, oxidative stress markers, and a neuronal aging marker (REST/NRSF) were investigated, and the intensity of fluorescence was quantified. The differences between the groups were assessed, and age-associated peripheral nerve changes were evaluated. Statistical analysis was performed using the Mann-Whitney U test. KEY FINDINGS: Although the number and density of axons did not differ significantly between the groups, they were lower in the aged group than in the young group. In addition, the fluorescence intensity of each marker did not differ significantly between the groups, but the expression of REST/NRSF alone was significantly higher in the aged group than in the young group (p < 0.05). SIGNIFICANCE: This study suggested that peripheral nerve functions are preserved by the expression of REST/NRSF, which increases with age. Because oxidative stress did not change, the protective effects of REST/NRSF are considered to be related to oxidative stress.