1. Academic Validation
  2. Age-dependent osteoprotective effects of hydroxytyrosol acetate: enhanced bone integrity via gut-bone axis activation

Age-dependent osteoprotective effects of hydroxytyrosol acetate: enhanced bone integrity via gut-bone axis activation

  • Food Funct. 2025 Dec 23. doi: 10.1039/d5fo02225h.
Fan Zhao 1 2 Jianhua Ma 1 3 Zhihao Chen 1 Dijie Li 1 4 Xiaoli Ma 1 5 Chaofei Yang 1 6 Jiangang Long 7 Airong Qian 1
Affiliations

Affiliations

  • 1 Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China. [email protected].
  • 2 Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.
  • 3 School of Public Health, Lanzhou University, Lanzhou, Gansu 730000, China.
  • 4 Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology, College of Life Sciences, Guangxi Normal University, Guilin, Guangxi, 541004, China.
  • 5 Department of Basic Medicine, School of Medicine, Xi'an International University, Xi'an, China.
  • 6 Puyang Institute of Technology, Henan University, Puyang, Henan 457000, China.
  • 7 Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.
Abstract

Osteoporosis, a disorder with reduced bone mass and biomechanical properties, poses a geriatric health challenge. Though natural Antioxidants like hydroxytyrosol acetate (HT-ac) have diverse regulatory effects, its impact on bone health is underexplored. This study examined HT-ac's age-specific effects on bone health in murine models. Mice were allocated to control and HT-ac groups, with the latter receiving HT-ac for 20 weeks. Assessments included bone density, microarchitecture, and biomechanical evaluation, alongside gut microbiota analysis and detection of Reactive Oxygen Species (ROS). Results showed HT-ac increased bone mineral content and improved trabecular properties in both age groups. However, young mice exhibited adverse effects including fat accumulation, inflammation, and elevated ROS levels, while such effects were absent in aged mice. Gut microbiota - metabolomic integration revealed HT-ac's osteoprotective effects correlated with gut microbiota changes and L-carnitine upregulation. Taken together, long-term HT-ac offers age-independent osteoprotection via gut microbiota-dependent L-carnitine biosynthesis. The differing outcomes highlight the need for age-specific strategies in osteoporosis intervention.

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