biostudies-literatureZhou YNatural Science Foundation of Zhejiang ProvinceYouth Cultivation Plan 'Cultivation Star Project' of Shanghai Jiao Tong University School of Medicine Affiliated Ruijin HospitalNational Natural Science Foundation of ChinaZhejiang Provincial Science and Technology Innovation ProgramZhejiang Provincial Science and Technology Innovation Program (New Young Talent Program) for College StudentsCharacteristic Directional S-Disciplines of The First Affiliated Hospital of Wenzhou Medical UniversityScience and Technology Project of WenzhouHealth Commission of Zhejiang Provincee70621https://www.ebi.ac.uk/biostudies/studies/S-EPMC12940804biostudies-literatureUnknown16(3)<h4>Background</h4>Ageing is a significant risk factor for pathophysiological alterations in the heart, but the intrinsic mechanisms by which these occur have yet to be fully elucidated. Purinergic 2×7 receptor (P2X7R) is important for the pathogenesis of numerous cardiovascular diseases; nevertheless, its function in the process of cardiac ageing remains uncertain.<h4>Methods</h4>This study utilised P2X7R knockout (P2X7R^-/^-) mice. An ageing model was established by either maintaining mice until they reached 20 months of age or performing chronic subcutaneous injection of D-galactose (D-gal). Recombinant adeno-associated virus serotype 9 (AAV9) was employed to achieve cardiac-specific overexpression of P2X7R and nuclear receptor subfamily 4 group A member 1 (NR4A1). CClinical and translational medicineP2X7R deficiency alleviates cardiac senescence by enhancing mitophagy via the HuR/TRIM26/NR4A1 axis.PMC129408042024R413C08980225018ZCLMS26H0201wyyy-2025S0282570459Y2024007082202380WKJ-ZJ-25402024PY192Y2023127Shen JZhang JYe BZhong XZhou YZhang WXing JYang ZHuang ZMei JChen YLin JWang YWang ZMao ZfalseP2X7R deficiency alleviates cardiac senescence by enhancing mitophagy via the HuR/TRIM26/NR4A1 axis.<h4>Background</h4>Ageing is a significant risk factor for pathophysiological alterations in the heart, but the intrinsic mechanisms by which these occur have yet to be fully elucidated. Purinergic 2×7 receptor (P2X7R) is important for the pathogenesis of numerous cardiovascular diseases; nevertheless, its function in the process of cardiac ageing remains uncertain.<h4>Methods</h4>This study utilised P2X7R knockout (P2X7R^-/^-) mice. An ageing model was established by either maintaining mice until they reached 20 months of age or performing chronic subcutaneous injection of D-galactose (D-gal). Recombinant adeno-associated virus serotype 9 (AAV9) was employed to achieve cardiac-specific overexpression of P2X7R and nuclear receptor subfamily 4 group A member 1 (NR4A1). C2026-01-01T00:00:00Z2026 Mar2026-07-16T21:55:48.395Z2026-07-10T03:16:26.906ZS-EPMC129408044174666810.1002/ctm2.70621