Background: Telomere attrition and dysregulation of telomere-related genes, including telomerase reverse transcriptase (TERT) and telomeric repeat-binding factors (TERF1/TERF2), have been implicated in skeletal muscle aging. Telomere attrition may induce the expression of factors involved in senescence such as cyclin-dependent kinase inhibitor 1A (CDKN1A). Objective: This study aimed to determine the correlation of CDKN1A expression, telomere regulatory genes (TERT, TERF1, and TERF2), and telomere length in skeletal muscle of D-galactose-induced aging rats. Methods: This in vivo study included two groups of Wistar rats (n = 5 per group). The aging group was induced by D-galactose (300 mg/kg BW, i.p.), while the control group was treated with 0.9% NaCl (2 mL, i.p.) for 6 weeks. Gene expression levels were quantified using RT-qPCR, and telomere length was assessed using qPCR-based absolute telomere length assay. Results: CDKN1A expression was higher in the aging group compared to controls (p < 0.01), whereas TERT expression was lower (p < 0.05). No significant differences were observed in TERF1 and TERF2 expression between groups. Telomere length was significantly shortened in the aging group (p < 0.05). Correlation analysis revealed an inverse association between CDKN1A and TERT expression (R = -0.71; p < 0.05). No significant correlations were found between CDKN1A and TERF1 or TERF2 (p > 0.05). In addition, CDKN1A expression was inversely correlated with telomere length (R = -0.9; p < 0.05). Conclusion: CDKN1A is inversely associated with TERT expression and telomere length in D-galactose–induced aging, suggesting a coordinated role in skeletal muscle aging.
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