{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:04:01Z","timestamp":1791396241314,"version":"4.3.3"},"reference-count":50,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Sarcopenia is an age-related condition marked by a progressive decline in muscle mass, weakened strength, and decreased physical performance in the elderly. Methods: In this research, we used D-galactose (D-gal)-induced 8-week-old male C57BL\/6J mice to establish a sarcopenia model. This model was utilized to investigate the effect and potential mechanism of \u03b1-ketoglutaric acid (AKG), a key intermediate of the tricarboxylic acid cycle, on sarcopenia. Results: Our findings demonstrated that AKG significantly ameliorated muscle mass, exercise endurance, grip strength, and cold tolerance in D-gal-induced aging mice. AKG could regulate protein homeostasis, thereby enhancing the protein composition and size of myofibers in D-gal-induced aging mice. Additionally, AKG enhanced SOD activity in the skeletal muscle of D-gal-induced aging mice and scavenged reactive oxygen species (ROS) by activating the SIRT1\/PGC-1\u03b1\/Nrf2 pathway, thereby improving mitochondrial function. Conclusions: In conclusion, AKG combated sarcopenia by regulating protein homeostasis and optimizing mitochondrial function in skeletal muscle. This study provides a scientific foundation for developing therapeutic interventions using AKG to target muscle aging.<\/jats:p>","DOI":"10.3390\/nu17213336","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T01:35:11Z","timestamp":1761269711000},"page":"3336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["\u03b1-Ketoglutarate Ameliorates Sarcopenia in D-Galactose-Induced Aging Mice by Modulating Protein Homeostasis and Optimizing Mitochondrial Function"],"prefix":"10.3390","volume":"17","author":[{"given":"Yangguang","family":"Zhang","sequence":"first","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Functional Dairy, Co-Constructed by Ministry of Education and Beijing Municipality, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintong","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Qiao","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","first-page":"499","article-title":"Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging","volume":"14","author":"Jing","year":"2023","journal-title":"Protein Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.bone.2015.02.008","article-title":"Skeletal muscle as an endocrine organ: PGC-1alpha, myokines and exercise","volume":"80","author":"Schnyder","year":"2015","journal-title":"Bone"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.arr.2018.07.005","article-title":"The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans","volume":"47","author":"Wilkinson","year":"2018","journal-title":"Ageing Res. 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