Combined physical exercise reverses the reduced expression of Bmal1 in the liver of aged mice

Author(s):Show less -

Pinto, Ana P. ; Munoz, Vitor R. ; Tavares, Maria Eduarda A. ; dos Santos, Jonathas R. ; Rebelo, Macario A. ; Alberici, Luciane C. ; Simabuco, Fernando M. ; Teixeira, Giovana R. ; Pauli, Jose R. ; de Moura, Leandro P. ; Cintra, Dennys E. ; Ropelle, Eduardo R. ; Freitas, Ellen C. ; Rivas, Donato A. ; da Silva, Adelino S. R.

• Document type: Journal article
• Source: Life Sciences; v. 312, p. 12-pg., 2023-01-01.

Abstract

Aging can modify the morphology and function of the liver, such as generating a decrease in the mitochondria content, autophagy, and cell senescence. Although exercise training has several beneficial effects on hepatic metabolism, its actions on autophagy processes, mitochondrial function, and cellular senescence need to be more widely explored. The present study verified the effects of aging and exercise on hepatic circadian markers, autophagy, and mitochondria activity in 24-month-old mice with a combined exercise training protocol. In addition, we used public datasets from human livers in several conditions and BMAL1 knockout mice. C57BL/6 mice were distributed into Control (CT, young, 6-month-old mice), sedentary old (Old Sed, sedentary, 24-month -old mice), and exercised old (Old Ex, 24-month-old mice submitted to a combined exercise training protocol). The exercise training protocol consisted of three days of endurance exercise - treadmill running, and two days of resistance exercise - climbing a ladder, for three weeks. At the end of the protocol, the liver was removed and prepared for histological analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunoblotting technique, and oxygen consumption. Heatmaps were built using a human dataset and Bmal1 knockout samples. In summary, the Old Sed had reduced strength, coordination, and balance, as well as a decrease in Bmal1 expression and the presence of degenerated liver cells. Still, this group upregulated the transcription factors related to mitochondrial biogenesis. The Old Ex group had increased strength, coordination, and balance, improved glucose sensitivity, as well as restored Bmal1 expression and the mitochondrial tran-scription factors. The human datasets indicated that mitochondrial markers and autophagy strongly correlate with specific liver diseases but not aging. We can speculate that mitochondrial and autophagy molecular markers alterations may depend on long-term training. (AU)

• FAPESP's process: 21/08693-1 - Effect of global or conditional deletion (skeletal muscle) of the Nr1d1 gene on aging
• Grantee: Ana Paula Pinto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/08692-5 - Analysis of the rev-erb-alpha protein interactome through immunoprecipitation of target protein and identification of possible ligands by mass spectrometry in cell culture
• Grantee: Vitor Rosetto Muñoz
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/13443-1 - Implications of aerobic exercise on the Notch 1 signaling pathway and regulation of lipogenesis and gluconeogenesis in the liver
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• 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: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Research Projects - Thematic Grants