EVALUATION OF SENESCENCE AND AUTOPHAGY OF OSTEOCYTES DURING AGING IN MIDDLE-AGED MALE AND FEMALE RATS TREATED WITH RESVERATROL

• Grant number: 24/13180-1
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Rinaldo Florencio da Silva
• Grantee: Rinaldo Florencio da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Estela Sasso Cerri ; Paulo Sergio Cerri
• Associated scholarship(s): 25/04501-1 - EVALUATION OF SENESCENCE AND AUTOPHAGY OF OSTEOCYTES DURING AGING IN MIDDLE-AGED MALE AND FEMALE RATS TREATED WITH RESVERATROL, BP.TT

Abstract

Studies indicate that there is increased senescence and reduced autophagy in osteocytes during aging, and that these changes are involved in bone loss associated with aging. It has been reported that resveratrol could reduce bone loss, although the cellular and molecular mechanisms are still poorly understood. Furthermore, the effects of these agents on osteocyte autophagy and senescence during aging have not yet been investigated. Therefore, in this study we intend to evaluate the effects of resveratrol on bone tissue and on the senescence and autophagy of osteocytes, in middle-aged male and female rats. Male and female Wistar rats aged 3 months (young) and 12 months ( middle age) will be used in this study. The middle-aged female rats will be ovariectomized (OVX) or Sham-operated (Sham) and after 30 days the animals will be divided into the following groups (G) of 6 animals each: Male (GI) and female (GII) young control rats; Middle-aged male rats treated with with vehicle solution (GIII) or with 80 mg/kg of resveratrol (GIV); Middle-aged Sham rats treated with vehicle solution (GV); Middle-aged OVX rats treated with vehicle solution (GVI), 10 µg/kg 17²-Estradiol (GVII) (Vakili et al. 2021), or with 80 mg/kg of resveratrol (GVIII). Young male and female rats will serve as a young control group for baseline data acquisition. After 12 weeks treatments, the rats will be euthanized and the long bones will be collected and processed for histological and ultrastructural analyzes. Bone tissue sections will be subjected to immunohistochemical/immunofluorescence, immunoelectron microscopy or in situ hybridization reactions to detect markers of autophagy and cellular senescence in osteocytes. Samples will also be processed for analysis of gene expression (qPCR) and protein expression (western blot) of these markers. Bioinformatics transcriptomic analyzes will also be performed. The data will be subjected to statistical analysis (pd0.05). (AU)