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

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 infusio...

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Main Authors: Yusaku Mori, Makoto Ohara, Michishige Terasaki, Naoya Osaka, Hironori Yashima, Tomomi Saito, Yurie Otoyama-Kataoka, Takemasa Omachi, Yuichiro Higashimoto, Takanori Matsui, Tomoyasu Fukui, Sho-ichi Yamagishi
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Language:English
Published: MDPI AG 2023-11-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/12/3112
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author Yusaku Mori
Makoto Ohara
Michishige Terasaki
Naoya Osaka
Hironori Yashima
Tomomi Saito
Yurie Otoyama-Kataoka
Takemasa Omachi
Yuichiro Higashimoto
Takanori Matsui
Tomoyasu Fukui
Sho-ichi Yamagishi
author_facet Yusaku Mori
Makoto Ohara
Michishige Terasaki
Naoya Osaka
Hironori Yashima
Tomomi Saito
Yurie Otoyama-Kataoka
Takemasa Omachi
Yuichiro Higashimoto
Takanori Matsui
Tomoyasu Fukui
Sho-ichi Yamagishi
author_sort Yusaku Mori
collection DOAJ
description 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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spelling doaj.art-2702c5b64a744305b3a937b78da3457c2023-12-22T13:54:41ZengMDPI AGBiomedicines2227-90592023-11-011112311210.3390/biomedicines11123112Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging MiceYusaku Mori0Makoto Ohara1Michishige Terasaki2Naoya Osaka3Hironori Yashima4Tomomi Saito5Yurie Otoyama-Kataoka6Takemasa Omachi7Yuichiro Higashimoto8Takanori Matsui9Tomoyasu Fukui10Sho-ichi Yamagishi11Anti-Glycation Research Section, Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDepartment of Chemistry, Kurume University School of Medicine, Kurume 830-0011, Fukuoka, JapanDepartment of Bioscience and Biotechnology, Fukui Prefectural University, Eiheiji 910-1195, Fukui, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanDivision of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8555, JapanWe 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.https://www.mdpi.com/2227-9059/11/12/3112AGEsDNA aptamerMuRF1muscle atrophyoxidative stresssarcopenia
spellingShingle Yusaku Mori
Makoto Ohara
Michishige Terasaki
Naoya Osaka
Hironori Yashima
Tomomi Saito
Yurie Otoyama-Kataoka
Takemasa Omachi
Yuichiro Higashimoto
Takanori Matsui
Tomoyasu Fukui
Sho-ichi Yamagishi
Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice
Biomedicines
AGEs
DNA aptamer
MuRF1
muscle atrophy
oxidative stress
sarcopenia
title Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice
title_full Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice
title_fullStr Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice
title_full_unstemmed Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice
title_short Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice
title_sort subcutaneous infusion of dna aptamer raised against advanced glycation end products prevents loss of skeletal muscle mass and strength in accelerated aging mice
topic AGEs
DNA aptamer
MuRF1
muscle atrophy
oxidative stress
sarcopenia
url https://www.mdpi.com/2227-9059/11/12/3112
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