Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 75, Issue 1, Pages 89-98Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glz177
Keywords
ITP; Life span; Aging; Adipose tissue; Macrophage
Categories
Funding
- Glenn Foundation for Medical Research
- National Institutes of Health (NIH) [AG022303, AG024824]
- Research Training in Experimental Immunology Training Grant [T32-AI007413]
- Career Training in the Biology of Aging Training Grant [T32-AG000114]
- Geriatrics Research, Education and Clinical Care Center (GRECC) of the VA Ann Arbor Healthcare System
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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-alpha 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-alpha estradiol do not strongly alter these phenotypes-suggesting that acarbose and 17- alpha estradiol may not influence life span through mechanisms involving adipose tissue inflammation.
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