, Volume 41, Issue 4, pp 395–408 | Cite as

Effect of caloric restriction and rapamycin on ovarian aging in mice

  • Driele N. Garcia
  • Tatiana D. Saccon
  • Jorgea Pradiee
  • Joao A. A. Rincón
  • Kelvin R. S. Andrade
  • Monique T. Rovani
  • Rafael G. Mondadori
  • Luis A. X. Cruz
  • Carlos C. Barros
  • Michal M. Masternak
  • Andrzej Bartke
  • Jeffrey B. Mason
  • Augusto Schneider
Original Article


Caloric restriction (CR) increases the preservation of the ovarian primordial follicular reserve, which can potentially delay menopause. Rapamycin also increases preservation on the ovarian reserve, with similar mechanism to CR. Therefore, the aim of our study was to evaluate the effects of rapamycin and CR on metabolism, ovarian reserve, and gene expression in mice. Thirty-six female mice were allocated into three groups: control, rapamycin-treated (4 mg/kg body weight every other day), and 30% CR. Caloric restricted females had lower body weight (P < 0.05) and increased insulin sensitivity (P = 0.003), while rapamycin injection did not change body weight (P > 0.05) and induced insulin resistance (P < 0.05). Both CR and rapamycin females displayed a higher number of primordial follicles (P = 0.02 and 0.04, respectively), fewer primary, secondary, and tertiary follicles (P < 0.05) and displayed increased ovarian Foxo3a gene expression (P < 0.05). Despite the divergent metabolic effects of the CR and rapamycin treatments, females from both groups displayed a similar increase in ovarian reserve, which was associated with higher expression of ovarian Foxo3a.


Rapamycin Ovarian reserve mTOR FOXO3a 


Authors’ contribution

CCB, MMM, AB, and AS designed research; DNG, TDS, JP, JAAR, and KRSA performed experiments; MTR, RGM, LAXC, MMM, and AS analyzed and interpreted data; DNG and AS wrote the manuscript, TDS, JP, JAAR, KRSA, MTR, RGM, LAXC, CCB, MMM, and AB revised the article.


This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) through a scholarship for DNG, TDS, JAAR, and JP; Fundação de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS); and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). This work was also supported by the National Institute on Aging (NIA) R15 AG059190 and R03 AG059846.

Compliance with ethical standards

This study was approved by the Committee on Ethics in Animal Experimentation of the Universidade Federal de Pelotas (UFPel), number 23110.009349/2016-31.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© American Aging Association 2019

Authors and Affiliations

  • Driele N. Garcia
    • 1
  • Tatiana D. Saccon
    • 1
  • Jorgea Pradiee
    • 2
  • Joao A. A. Rincón
    • 2
  • Kelvin R. S. Andrade
    • 1
  • Monique T. Rovani
    • 2
  • Rafael G. Mondadori
    • 3
  • Luis A. X. Cruz
    • 3
  • Carlos C. Barros
    • 1
  • Michal M. Masternak
    • 4
    • 5
  • Andrzej Bartke
    • 6
  • Jeffrey B. Mason
    • 7
  • Augusto Schneider
    • 1
  1. 1.Faculdade de NutriçãoUniversidade Federal de PelotasPelotasBrazil
  2. 2.Faculdade de Medicina VeterináriaUniversidade Federal de PelotasPelotasBrazil
  3. 3.Instituto de BiologiaUniversidade Federal de PelotasPelotasBrazil
  4. 4.College of Medicine, Burnett School of Biomedical SciencesUniversity of Central FloridaOrlandoUSA
  5. 5.Department of Head and Neck SurgeryThe Greater Poland Cancer CentrePoznanPoland
  6. 6.Departments of Internal Medicine and PhysiologySouthern Illinois University School of MedicineSpringfieldUSA
  7. 7.Department of Animal, Dairy and Veterinary Sciences, Center for Integrated BioSystems, School of Veterinary MedicineUtah State UniversityLoganUSA

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