Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging.

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

Institut Hospitalo-Universitaire (IHU) HealthAge, Toulouse, France. · pubmed

Paper

Abstract

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.

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Research summary

The paper investigates biological aging through a comprehensive analysis of a mouse cohort, focusing on sex-specific functional determinants and identifying critical markers of biological aging. This aligns with longevity research as it seeks to understand the underlying mechanisms of aging rather than merely addressing age-related diseases. However, while the findings are solid and contribute to the understanding of biological aging, they do not present groundbreaking insights that would significantly advance the field, hence the moderate impact score.

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