Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging
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.
Authors
- Sophie Guyonnet (ORCID: https://orcid.org/0000-0001-9527-5282)
- Cédrick Florian (ORCID: https://orcid.org/0000-0001-5634-7992)
- Sébastien Gauzin
- Ryeonshi Kang (ORCID: https://orcid.org/0000-0001-5709-128X)
- Mara Rigamonti (ORCID: https://orcid.org/0000-0002-3913-4458)
- Rana Zahreddine (ORCID: https://orcid.org/0000-0003-1291-6879)
- Philipe de Souto Barreto (ORCID: https://orcid.org/0000-0002-8860-425X)
- Bruno P. Guiard (ORCID: https://orcid.org/0000-0002-6873-9966)
- Angelo Parini (ORCID: https://orcid.org/0000-0002-9848-8838)
- Yohan Santin (ORCID: https://orcid.org/0000-0002-9229-1161)
- Mégane Guardia
- Mattia Chiesa (ORCID: https://orcid.org/0000-0001-7427-9954)
- Yves Rolland (ORCID: https://orcid.org/0009-0003-9486-9144)
- Giorgio Rosati (ORCID: https://orcid.org/0009-0006-0582-9450)
- Fraha Haidar
- Amélie Alfonso
- Bruno Vellas
- Yosra Doghri
- Lucas Lemmel
- Pilar Oreja-Fuentes
- Occiane Fousset
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Centre de Recherches en Cancérologie de Toulouse (FR)
- Centro Cardiologico Monzino (IT)
- Centre de Recherches sur la Cognition Animale (FR)
- Institut des Maladies Métaboliques et Cardiovasculaires (FR)
- Institut de Mathématiques de Toulouse (FR)
- Politecnico di Milano (IT)
Publication Details
- Journal
- Science Advances
- Published
- 2024-12-13
- DOI
- https://doi.org/10.1126/sciadv.adt1670
- Citations
- 3
- Primary Topic
- Metabolomics and Mass Spectrometry Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.70