Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice

被引:4
|
作者
Mori, Yusaku [1 ]
Ohara, Makoto [2 ]
Terasaki, Michishige [2 ]
Osaka, Naoya [2 ]
Yashima, Hironori [2 ]
Saito, Tomomi [2 ]
Otoyama-Kataoka, Yurie [2 ]
Omachi, Takemasa [2 ]
Higashimoto, Yuichiro [3 ]
Matsui, Takanori [4 ]
Fukui, Tomoyasu [2 ]
Yamagishi, Sho-ichi [2 ]
机构
[1] Showa Univ, Antiglycat Res Sect, Div Diabet Metab & Endocrinol, Dept Med,Sch Med, Shinagawa, Tokyo 1428555, Japan
[2] Showa Univ, Dept Med, Div Diabet Metab & Endocrinol, Sch Med, Shinagawa, Tokyo 1428555, Japan
[3] Kurume Univ, Sch Med, Dept Chem, Fukuoka 8300011, Japan
[4] Fukui Prefectural Univ, Dept Biosci & Biotechnol, Fukui 9101195, Japan
关键词
AGEs; DNA aptamer; MuRF1; muscle atrophy; oxidative stress; sarcopenia; 1 NULL MICE; OXIDATIVE DAMAGE; AGE; PROGRESSION; DISABILITY; DISEASES; PATHWAY; ATROPHY; BLOCKS; GROWTH;
D O I
10.3390/biomedicines11123112
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have developed DNA aptamers that can inhibit the toxic effects of advanced glycation end products (AGE-Apts). We herein evaluated the effects of AGE-Apts on muscle mass and strength in senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old male SAMP8 mice received subcutaneous infusion of control DNA aptamers (CTR-Apts) or AGE-Apts. Mice in an age-matched senescence-accelerated mouse resistant strain 1 (SAMR1) group were treated with CTR-Apts as controls. The soleus muscles were collected after the 8-week intervention for weight measurement and histological, RT-PCR, and immunofluorescence analyses. Grip strength was measured before and after the 8-week intervention. AGE-Apt treatment inhibited the progressive decrease in the grip strength of SAMP8 mice. SAMP8 mice had lower soleus muscle weight and fiber size than SAMR1 mice, which was partly restored by AGE-Apt treatment. Furthermore, AGE-Apt-treated SAMP8 mice had a lower interstitial fibrosis area of the soleus muscle than CTR-Apt-treated SAMP8 mice. The soleus muscle levels of AGEs, oxidative stress, receptor for AGEs, and muscle ring-finger protein-1 were increased in the CTR-Apt-treated mice, all of which, except for AGEs, were inhibited by AGE-Apt treatment. Our present findings suggest that the subcutaneous delivery of AGE-Apts may be a novel therapeutic strategy for aging-related decrease in skeletal muscle mass and strength.
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页数:13
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