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Updated: Aug 27, 2025
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Dicer1 deficient mice exhibit premature aging and metabolic perturbations in adipocytes
Aurore De Cauwer1, Thomas Loustau1, William Erne1
1Laboratoire d'ImmunoRhumatologie Moléculaire, Institut national de la santé et de la recherche médicale (INSERM) UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
Abstract:
Age-related diseases are major concern in developed countries. To avoid disabilities that accompany increased lifespan, pharmaceutical approaches are considered. Therefore, appropriate animal models are required for a better understanding of aging processes and potential in vivo assays to evaluate the impact of molecules that may delay the occurrence of age-related diseases. Few mouse models exhibiting pathological aging exist, but currently, none of them reproducibly mimics human diseases like osteoporosis, cognitive dysfunctions or sarcopenia that can be seen in some, but not all, elders. Here, we describe the premature aging phenotypes of Dicer-deficient mature animals, which exhibit an overall deterioration of many organs and tissues (skin, heart, and adipose tissue) ultimately leading to a significant reduction of their lifespan. Molecular characterization of transcriptional responses focused on the adipose tissue suggested that both canonical and non-canonical functions of DICER are involved in this process and highlight potential actionable pathways to revert it.
Insights
Dicer-deficient mice exhibit premature aging, organ deterioration, and reduced lifespan. This model highlights DICER
Area of Science:
- Molecular biology
- Gerontology
- Genetics
Background:
- Age-related diseases pose significant challenges in developed nations.
- Pharmaceutical interventions are explored to mitigate age-related disabilities.
- Existing animal models inadequately replicate human aging pathologies.
Purpose of the Study:
- To investigate the role of DICER in aging processes.
- To characterize premature aging phenotypes in Dicer-deficient mice.
- To identify molecular pathways involved in age-related deterioration.
Main Methods:
- Generation and analysis of Dicer-deficient mature mice.
- Assessment of organ and tissue health (skin, heart, adipose tissue).
- Molecular characterization of transcriptional responses in adipose tissue.
Main Results:
- Dicer deficiency leads to premature aging phenotypes.
- Significant deterioration observed in multiple organs and tissues.
- Reduced lifespan in Dicer-deficient animals.
- Identification of both canonical and non-canonical DICER functions in aging.
Conclusions:
- Dicer-deficient mice present a novel model for studying premature aging.
- DICER plays a critical role in maintaining tissue homeostasis during aging.
- Potential therapeutic pathways to counteract aging were identified.
