Two-phase model of ageing in mice for improved identification of age-related and late life metabolic decline

Living animals reach their end-of-life through a stereotypic set of fascinating but poorly understood processes. The discovery, first in flies and later in nematodes and zebrafish, of the "Smurf phenotype" has provided a valuable tool to investigate ageing and its associated physiological changes. Using the Smurfs, we have shown an evolutionarily conserved end-of-life transition across Drosophilids, nematodes, and zebrafish. This tool has been key to identify the discontinuous nature of ageing and predict impending death from natural causes as well as from environmental stresses. This phenotype led us to propose a two-phase perspective of ageing: a first phase where individuals are apparently healthy and have low risk of mortality, but show an age-dependent and increasing risk of entering a second phase, marked by more pronounced hallmarks of ageing and a markedly increased risk of death. Here, we test whether these two consecutive phases of ageing separated by the Smurf transition are a conserved feature of ageing in the mammals using Mus musculus as a model. We performed a longitudinal longevity study using both males and females from two different mouse genetic backgrounds and by integrating physiological, metabolic, and molecular measurements with the life history of approximately 150 mice. We show the existence of a phenotypic signature typical of the last phase of life, observable at any chronological age. Validating the two-phase ageing model in a mammalian organism allows better characterization of the high risk of imminent death and would extend its implications to a broader range of species for ageing research. The Stage 1 version of this Registered Report was submitted on 19th January 2022.

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Publication Details

Journal
BMC Biology
Published
2025-10-22
DOI
https://doi.org/10.1186/s12915-025-02421-6
Citations
2
Primary Topic
Adipose Tissue and Metabolism
Type
article
Field-Weighted Citation Impact
2.33

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article

Two-phase model of ageing in mice for improved identification of age-related and late life metabolic decline

Magali Monnoye, Serge Luquet, Clara Sanchez, Céline Cansell et al.
2 citations
BMC Biology
Adipose Tissue and Metabolism
2.33
article

Two-phase model of ageing in mice for improved identification of age-related and late life metabolic decline

Magali Monnoye, Serge Luquet, Clara Sanchez, Céline Cansell, R Denis, Nicolas Todd, Flaminia Zane, Vivien Goepp, Carole Rovère, Nicolas Pietrancosta, Véronique Douard, Fanny Bain, Michaël Rera
article en
2 citations

Abstract

Living animals reach their end-of-life through a stereotypic set of fascinating but poorly understood processes. The discovery, first in flies and later in nematodes and zebrafish, of the "Smurf phenotype" has provided a valuable tool to investigate ageing and its associated physiological changes. Using the Smurfs, we have shown an evolutionarily conserved end-of-life transition across Drosophilids, nematodes, and zebrafish. This tool has been key to identify the discontinuous nature of ageing and predict impending death from natural causes as well as from environmental stresses. This phenotype led us to propose a two-phase perspective of ageing: a first phase where individuals are apparently healthy and have low risk of mortality, but show an age-dependent and increasing risk of entering a second phase, marked by more pronounced hallmarks of ageing and a markedly increased risk of death. Here, we test whether these two consecutive phases of ageing separated by the Smurf transition are a conserved feature of ageing in the mammals using Mus musculus as a model. We performed a longitudinal longevity study using both males and females from two different mouse genetic backgrounds and by integrating physiological, metabolic, and molecular measurements with the life history of approximately 150 mice. We show the existence of a phenotypic signature typical of the last phase of life, observable at any chronological age. Validating the two-phase ageing model in a mammalian organism allows better characterization of the high risk of imminent death and would extend its implications to a broader range of species for ageing research. The Stage 1 version of this Registered Report was submitted on 19th January 2022.

BMC BiologyVol. 23(1)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), AgroParisTech (FR), Université Paris Sciences et Lettres (FR), Université Paris-Saclay (FR), École Normale Supérieure - PSL (FR), Microbiologie de l’alimentation au service de la santé (FR), Sorbonne Université (FR), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Sorbonne Paris Cité (FR), Institut de Biologie Paris-Seine (FR), Max Planck Institute for Demographic Research (DE), Muséum national d'Histoire naturelle (FR), Unit of Functional and Adaptive Biology (FR), Institut Cochin (FR), Hôpital Saint-Michel (FR), Institut de Pharmacologie Moléculaire et Cellulaire (FR), Laboratoire des Biomolécules (FR), Neurosciences Paris-Seine (FR), Université Paris 1 Panthéon-Sorbonne (FR), École Nationale Supérieure des Mines de Paris (FR), Institut Curie (FR)
Agence Nationale de la Recherche, Centre National de la Recherche Scientifique, Fondation Bettencourt Schueller, Sorbonne Université
Openalex Percentile: Top 10%
Adipose Tissue and Metabolism
2.33
DOIOpen Access PDFOpenAlex
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