Ma Xueling, Ding Yonghe, Mondaca-Ruff David, Zhang Xinyue, Lu Yu, Yoon Baul, Yan Feixiang, Liang Yanyan, Moossavi Maryam, Xu Xiaolei
Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
School of Nursing, Beijing University of Chinese Medicine, Beijing, China.
NPJ Aging. 2025 Jul 11;11(1):63. doi: 10.1038/s41514-025-00253-w.
African turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate that can be bred in captivity, making it an ideal model organism for aging studies. However, whether the animal can be used for studying cardiac aging and whether cellular senescence contribute to this ageing process remain unclear. Here, we conducted a longitudinal study on the GRZ strain, aiming to identify phenotypic and functional markers for cardiac aging. We found that cardiac ageing in GRZ fish can be measured by comparing fish at 16 weeks to 8 weeks of age, using systemic markers such as body/fin coloration, body weight, BMI, cardiac ageing markers such as EF, E/A ratio, and swimming capacity, and cellular senescence markers such as SA-β-gal staining, p15/p16, γ-H2A.X, and SASP markers. Senolytic treatment with D (Dasatinib) and Q (Quercetin) from 12 to 16 weeks mitigated senescence and decelerated cardiac ageing. Together, our findings established GRZ as a useful vertebrate model for studying cardiac ageing and related cardiac senescence.
非洲青鳉(Nothobranchius furzeri)是寿命最短的可在圈养条件下繁殖的脊椎动物,这使其成为衰老研究的理想模式生物。然而,这种动物是否可用于研究心脏衰老以及细胞衰老是否促成这一衰老过程仍不清楚。在此,我们对GRZ品系进行了一项纵向研究,旨在确定心脏衰老的表型和功能标志物。我们发现,通过比较16周龄和8周龄的GRZ鱼,利用诸如身体/鳍的颜色、体重、BMI等全身标志物、诸如射血分数(EF)、E/A比值等心脏衰老标志物以及游泳能力,以及诸如衰老相关β-半乳糖苷酶(SA-β-gal)染色、p15/p16、γ-H2A.X和衰老相关分泌表型(SASP)标志物等细胞衰老标志物,可以衡量GRZ鱼的心脏衰老情况。在12至16周龄时用达沙替尼(D)和槲皮素(Q)进行衰老细胞清除治疗可减轻衰老并减缓心脏衰老。总之,我们的研究结果确立了GRZ作为研究心脏衰老及相关心脏细胞衰老的有用脊椎动物模型。