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Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging.

Authors
  • Mau, Theresa1, 2
  • O'Brien, Martin1
  • Ghosh, Amiya K1
  • Miller, Richard A3
  • Yung, Raymond1, 2, 3, 4
  • 1 Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor.
  • 2 Graduate Program in Immunology, Program in Biomedical Sciences (PIBS), University of Michigan, Ann Arbor.
  • 3 Department of Pathology and Glenn Center for Biology of Aging Research, University of Michigan, Ann Arbor.
  • 4 Geriatric Research, Education, and Clinical Care Center (GRECC), VA Ann Arbor Health System, Michigan.
Type
Published Article
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
Publication Date
Jan 01, 2020
Volume
75
Issue
1
Pages
89–98
Identifiers
DOI: 10.1093/gerona/glz177
PMID: 31353414
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The National Institute on Aging (NIA)-sponsored Interventions Testing Program (ITP) has identified a number of dietary drug interventions that significantly extend life span, including rapamycin, acarbose, and 17-α estradiol. However, these drugs have diverse downstream targets, and their effects on age-associated organ-specific changes are unclear (Nadon NL, Strong R, Miller RA, Harrison DE. NIA Interventions Testing Program: investigating putative aging intervention agents in a genetically heterogeneous mouse model. EBioMedicine. 2017;21:3-4. doi:10.1016/j.ebiom.2016.11.038). Potential mechanisms by which these drugs extend life could be through their effect on inflammatory processes often noted in tissues of aging mice and humans. Our study focuses on the effects of three drugs in the ITP on inflammation in gonadal white adipose tissue (gWAT) of HET3 mice-including adiposity, adipose tissue macrophage (ATM) M1/M2 polarization, markers of cellular senescence, and endoplasmic reticulum stress. We found that rapamycin led to a 56% increase of CD45+ leukocytes in gWAT, where the majority of these are ATMs. Interestingly, rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206-) ATMs in females and males, respectively. Our data suggest rapamycin may achieve life-span extension in part through adipose tissue inflammation. Additionally, HET3 mice exhibit a spectrum of age-associated changes in the gWAT, but acarbose and 17-α estradiol do not strongly alter these phenotypes-suggesting that acarbose and 17- α estradiol may not influence life span through mechanisms involving adipose tissue inflammation. © The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: [email protected]

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