‎‌The‌‎ ‎‌effect‌‎ ‎‌of‌‎ ‎‌high‌‎-‎‌intensity‌‎ ‎‌interval‌‎ ‎‌training‌‎ ‎‌on‌‎ ‎‌p53‌‎ ‎‌and‌‎ ‎‌p16‌‎ ‎‌genes‌‎ ‎‌expression‌‎ ‎‌in‌‎ ‎‌pancreatic‌‎ ‎‌tissue‌‎ ‎‌of‌‎ ‎‌aged‌‎ ‎‌rats‌‎ 
‎‌fed‌‎ ‎‌with‌‎ ‎‌high‌‎-‎‌fat‌‎ ‎‌diet‌‎

Jamshidi‏‎, Masumeh; Nazarali, Parvaneh; Rezaeinezhad, Najmeh

doi:10.22034/26.4.31

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Volume 26, Issue 4 (Winter 2024)

EBNESINA 2024, 26(4): 31-41

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‎‌The‌‎ ‎‌effect‌‎ ‎‌of‌‎ ‎‌high‌‎-‎‌intensity‌‎ ‎‌interval‌‎ ‎‌training‌‎ ‎‌on‌‎ ‎‌p53‌‎ ‎‌and‌‎ ‎‌p16‌‎ ‎‌genes‌‎ ‎‌expression‌‎ ‎‌in‌‎ ‎‌pancreatic‌‎ ‎‌tissue‌‎ ‎‌of‌‎ ‎‌aged‌‎ ‎‌rats‌‎ ‎‌fed‌‎ ‎‌with‌‎ ‎‌high‌‎-‎‌fat‌‎ ‎‌diet‌‎

Masumeh Jamshidi‏‎

, Parvaneh Nazarali

, Najmeh Rezaeinezhad ^*

Department‏‎ ‎‏of‏‎ ‎‏Exercise‏‎ ‎‏Physiology‏‎, ‎‏Faculty‏‎ ‎‏of‏‎ ‎‏Sport‏‎ ‎‏Sciences‏‎, ‎‏University‏‎ ‎‏of‏‎ ‎‏Tehran‏‎, ‎‏Tehran‏‎, ‎‏Iran‏‎ , n.rezaeinezhad@ut.ac.ir

Keywords: ‎‌High‌‎-‎‌Intensity‌‎ ‎‌Interval‌‎ ‎‌Training‌‎, ‎‌Cellular‌‎ ‎‌Senescence‌‎, ‎‌Obesity‌‎, ‎‌p53‌‎ ‎‌Genes‌‎, ‎‌p16‌‎ ‎‌Genes‌‎

Full-Text [PDF 2065 kb] (247 Downloads) | Abstract (HTML) (954 Views)

Type of Study: Original | Subject: Military Medicine
Received: 2024/09/7 | Revised: 2025/03/12 | Accepted: 2024/10/27 | Published: 2024/12/21

Extended Abstract: (359 Views)

Introduction

The natural aging process is associated with a gradual loss of homeostasis, leading to various physiological changes in cell and tissue function [1]. As individuals age and become senile, oxidative stress increases, resulting in muscle dysfunction and atrophy. To mitigate oxidative stress, cells can prevent damage by halting the cell cycle through the activation of aging markers, specifically the tumor suppressor proteins P53 and p16 [2]. Both P53 and p16 are recognized as markers of aging, with studies showing that their expression increases with age. P53 regulates various biological processes, including stress response, cell cycle, proliferation, aging, and apoptosis. The expression of the p16 gene occurs in most senescent cells, where it acts as a cyclin-dependent kinase inhibitor and tumor suppressor, leading to growth arrest. It has been reported that p16 may play a role in regulating the transcription of age-dependent factors in cells [5]. Physical activity is recognized as a lifestyle intervention with anti-aging effects [6]; however, the exercise response remains unclear, with reports suggesting that it depends on factors such as cellular location, duration, and intensity of the stimulus. Therefore, the present study aimed to investigate the effect of eight weeks of high-intensity interval training (HIIT) on P53 and P16 gene expression in the pancreatic tissue of mice fed a high-fat diet.

Methods

This experimental study employed a post-test design with a control group. Twenty male Wistar rats, aged 52 weeks, were maintained in standard cages at 22±2°C. The animals were divided into four weight-matched groups: a normal diet group, a normal diet + training group, a high-fat diet group, and a high-fat diet + training group. The animals had free access to water and food and were fed either a high-fat diet (60% fat) or a standard diet. All care and ethical principles were fully adhered to according to laboratory animal care and use guidelines, and the research was approved by the ethics committee. The HIIT protocol was implemented three days per week, with each session lasting 22 minutes, consisting of four minutes of running at 45-55% VO₂max intensity, nine intervals of one minute at 90-95% VO₂max intensity, with one minute of running at 50% VO₂max intensity between each interval [18].
The rats were sacrificed 48 hours after the final training session, following 12 hours of fasting, and the pancreatic tissue was rapidly isolated. For gene expression analysis using real-time PCR, all primers were designed using Allele ID v7.8 software (Macrogen Inc., Seoul, South Korea), with β2m (beta-2 microglobulin) used as an internal control. Data were analyzed using one-way analysis of variance at a significance level of p<0.05.

Results

The results revealed significant differences in P53 gene expression among the four groups (p=0.0001). Bonferroni post-hoc test results indicated significant differences between the normal diet group and the high-fat diet group (p=0.001), between the normal diet+ training group and the high-fat diet+ training group (p=0.013), and between the normal diet+ training group and the high-fat diet group (p=0.0001). Furthermore, one-way analysis of variance showed significant differences in P16 levels among the four groups (p=0.003). P16 gene expression levels also showed significant differences between the normal diet group and the high-fat diet group (p=0.017), and between the normal diet+ training group and the high-fat diet group (p=0.006). The results demonstrated that exercise led to a decrease in P53 and P16 expression, while a high-fat diet caused an increase in these factors.

Discussion and Conclusion

The results of the present study indicate that HIIT training significantly decreased the relative expression of the P16 and P53 genes in the pancreatic tissue of aged mice fed a high-fat diet. In contrast, the control group (which did not undergo training and was fed a normal diet or a high-fat diet) exhibited higher levels of expression for these genes. Supporting these findings, Dashtiyan et al. reported that continuous and intense interval training reduces the expression of the tumor suppressor genes P53 and PTEN [15]. In contrast, Abdollahi Diba et al. found that endurance training had no significant impact on the expression of cytochrome C and P53 genes in the heart muscle of male rats [11].
These findings indicate that HIIT positively affects the expression of P53 and P16 in the pancreatic tissue of elderly rats fed a high-fat diet. In the training groups, we observed decreased expression of P53 and P16 in the pancreatic tissue, while the high-fat diet groups exhibited increased expression of these factors. These results suggest an improvement in pancreatic tissue health and a reduction in the negative effects of a high-fat diet.

Ethical Considerations

In the present study, the use of laboratory animals complied with international guidelines for the care and use of laboratory animals. The protocol was also approved by the Research Ethics Committee of Ilam University (Code:IR.ILAM.REC.1402.020).

Funding

There is no funding support.

Authors’ Contribution

Authors contributed equally to the conceptualization and writing of the article. All of the authors approved the content of the manuscript and agreed on all aspects of the work.

Conflict of Interest

Authors declared no conflict of interest.

Acknowledgments

We are grateful to all the persons for scientific consulting in this paper.

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Jamshidi‏‎ M, Nazarali P, Rezaeinezhad N. ‎‌The‌‎ ‎‌effect‌‎ ‎‌of‌‎ ‎‌high‌‎-‎‌intensity‌‎ ‎‌interval‌‎ ‎‌training‌‎ ‎‌on‌‎ ‎‌p53‌‎ ‎‌and‌‎ ‎‌p16‌‎ ‎‌genes‌‎ ‎‌expression‌‎ ‎‌in‌‎ ‎‌pancreatic‌‎ ‎‌tissue‌‎ ‎‌of‌‎ ‎‌aged‌‎ ‎‌rats‌‎ ‎‌fed‌‎ ‎‌with‌‎ ‎‌high‌‎-‎‌fat‌‎ ‎‌diet‌‎. EBNESINA 2024; 26 (4) :31-41
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