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Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging
Science Advances ( IF 11.7 ) Pub Date : 2024-12-13 , DOI: 10.1126/sciadv.adt1670
Yohan Santin, Mattia Chiesa, Amélie Alfonso, Yosra Doghri, Ryeonshi Kang, Fraha Haidar, Pilar Oreja-Fuentes, Occiane Fousset, Rana Zahreddine, Mégane Guardia, Lucas Lemmel, Mara Rigamonti, Giorgio Rosati, Cédrick Florian, Sébastien Gauzin, Sophie Guyonnet, Yves Rolland, Philipe de Souto Barreto, Bruno Vellas, Bruno Guiard, Angelo Parini

Biological age, which reflects the physiological state of an individual, offers a better predictive value than chronological age for age-related diseases and mortality. Nonetheless, determining accurate functional features of biological age remains challenging due to the multifactorial nature of aging. Here, we established a unique mouse cohort comprising 1576 male and female outbred SWISS mice subjected or not to high-fat, high-sucrose diet to investigate multiorgan/system biological aging throughout adulthood. Comprehensive functional and biological phenotyping at ages of 6, 12, 18, and 24 months revealed notable sex-specific disparities in longitudinal locomotion patterns and multifunctional aging parameters. Topological data analysis enabled the identification of functionally similar mouse clusters irrespective of chronological age. Moreover, our study pinpointed critical functional markers of biological aging such as muscle function, anxiety characteristics, urinary patterns, reticulocyte maturation, cardiac remodeling and function, and metabolic alterations, underscoring muscle function as an early indicator of biological age in male mice.

中文翻译:


INSPIRE 小鼠队列中的计算和数字分析,以确定生物衰老的性别特异性功能决定因素



生物年龄反映了个体的生理状态,对于与年龄相关的疾病和死亡率,生物年龄比实际年龄具有更好的预测价值。尽管如此,由于衰老的多因素性质,确定生物年龄的准确功能特征仍然具有挑战性。在这里,我们建立了一个独特的小鼠队列,由 1576 只雄性和雌性近交 SWISS 小鼠组成,这些小鼠接受或不接受高脂肪、高蔗糖饮食,以研究整个成年期的多器官/系统生物衰老。6 、 12 、 18 和 24 个月龄的综合功能和生物学表型显示纵向运动模式和多功能衰老参数的显着性别特异性差异。拓扑数据分析能够识别功能相似的小鼠簇,而与实际年龄无关。此外,我们的研究确定了生物衰老的关键功能标志物,例如肌肉功能、焦虑特征、尿路模式、网织红细胞成熟、心脏重塑和功能以及代谢改变,强调肌肉功能是雄性小鼠生物年龄的早期指标。
更新日期:2024-12-13
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