Combined physical exercise re-synchronizes expression of Bmal1 and REV-ERBα and up-regulates apoptosis and metabolism in the prostate during aging

Author(s)

Tavares, Maria Eduarda Almeida ; Pinto, Ana Paula ; da Rocha, Alisson Luiz ; Sampaio, Larissa Victorino ; Correia, Rafael Ribeiro ; Batista, Victor Rogerio Garcia ; Veras, Allice Santos Cruz ; Chaves-Neto, Antonio Hernandes ; da Silva, Adelino Sanchez Ramos ; Teixeira, Giovana Rampazzo

• Document type: Journal article
• Source: Life Sciences; v. 351, p. 12-pg., 2024-06-17.

Abstract

Background: Aging increases the prevalence of prostate cancer. The circadian clock coordinates metabolism, cell cycle, and tumor suppressor p53. Although physical exercise has several effects on preventing prostate diseases, its effect on regulating genes and proteins of the circadian rhythm of the prostate needs to be better evaluated. The present study verified expression of REV-ERB alpha (Nr1d1), Bmal1, apoptosis, tumor suppressors, energetic metabolism markers, and androgen receptors in the prostatic microenvironment in 18-month-old mice submitted to combined physical training. Methods: C57BL/6 J mice were divided into 2 groups: 6 months-old (n = 10) and 18 months-old, (n = 20). The 18-month-old animals were divided into 2 subgroups: sedentary (n = 10, 18 m Sed) and submitted to combined physical training (n = 10, 18 m TR). Combined physical training protocol was performed by running on the treadmill (40-60 % of incremental load test) and climbing strength training (40-50 % of maximum repetition test), consisting of 5x/week (3 days aerobic and 2 days strength) for 3 weeks. The prostate was prepared for Western blot and RT-qPCR analysis, and the plasm was prepared for the biochemistry analysis. Results: Combined physical exercise during aging led to increased levels of Bmal1 and decreased levels of REVERB alpha in the prostate. These results were accompanied by a reduction in the AMPK/SIRT1/PGC-1 alpha proteins and an increase in the PI3K/AKT and p53/PTEN/caspase 3 pathways, promoting apoptotic potential. Conclusion: These findings suggest that strength and aerobic physical exercise may be preventive in the development of preneoplastic molecular alterations and age-related features by re-synchronizes Bmal1 and REV-ERB alpha in prostatic tissues. (AU)

• FAPESP's process: 21/06291-3 - Multi-user Equipament approved in grant 2019/11820-5: ChemiDoc Imaging System and accessories
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 22/06807-2 - Interrelationship of interleukin-6 and kynurenine pathway in cognitive and behavioral disorders induced by excessive exercise: in vivo and in vitro models
• Grantee: Alisson Luiz da Rocha
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/16310-2 - Development of biotechnology applied to prostatic carcinomatosis with the use of Docetaxel chemotherapy care nanoparticles associated with aerobic physical training
• Grantee: Giovana Rampazzo Teixeira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Research Projects - Thematic Grants