Rapamycin increases mortality in db/db mice, a mouse model of type 2 diabetes

Kavithalakshmi Sataranatarajan, Yuji Ikeno, Alex Bokov, Denis Feliers, Himabindu Yalamanchili, Hak Joo Lee, Meenalakshmi M. Mariappan, Hooman Tabatabai-Mir, Vivian Diaz, Sanjay Prasad, Martin A. Javors, Goutam Ghosh Choudhury, Gene B. Hubbard, Jeffrey L. Barnes, Arlan Richardson, Balakuntalam S. Kasinath

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

We examined the effect of rapamycin on the life span of a mouse model of type 2 diabetes, db/db mice. At 4 months of age, male and female C57BLKSJ-leprdb/db mice (db/db) were placed on either a control diet, lacking rapamycin or a diet containing rapamycin and maintained on these diets over their life span. Rapamycin was found to reduce the life span of the db/db mice. The median survival of male db/db mice fed the control and rapamycin diets was 349 and 302 days, respectively, and the median survival of female db/db mice fed the control and rapamycin diets was 487 and 411 days, respectively. Adjusting for gender differences, rapamycin increased the mortality risk 1.7-fold in both male and female db/db mice. End-of-life pathological data showed that suppurative inflammation was the main cause of death in the db/db mice, which is enhanced slightly by rapamycin treatment.

Original languageEnglish (US)
Pages (from-to)850-857
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume71
Issue number7
DOIs
StatePublished - Jul 2016

Keywords

  • Life span
  • Obesity
  • Toxicity
  • mTOR inhibition

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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