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Thioredoxin overexpression in both the cytosol and mitochondria accelerates age-related disease and shortens lifespan in male C57BL/6 mice

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Abstract

To investigate the role of increased levels of thioredoxin (Trx) in both the cytosol (Trx1) and mitochondria (Trx2) on aging, we have conducted a study to examine survival and age-related diseases using male mice overexpressing Trx1 and Trx2 (TXNTg × TXN2Tg). Our study demonstrated that the upregulation of Trx in both the cytosol and mitochondria in male TXNTg × TXN2Tg C57BL/6 mice resulted in a significantly shorter lifespan compared to wild-type (WT) mice. Cross-sectional pathology data showed a slightly higher incidence of neoplastic diseases in TXNTg × TXN2Tg mice than WT mice. The incidence of lymphoma, a major neoplastic disease in C57BL/6 mice, was slightly higher in TXNTg × TXN2Tg mice than in WT mice, and more importantly, the severity of lymphoma was significantly higher in TXNTg × TXN2Tg mice compared to WT mice. Furthermore, the total number of histopathological changes in the whole body (disease burden) was significantly higher in TXNTg × TXN2Tg mice compared to WT mice. Therefore, our study suggests that overexpression of Trx in both the cytosol and mitochondria resulted in deleterious effects on aging and accelerated the development of age-related diseases, especially cancer, in male C57BL/6 mice.

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Acknowledgements

We acknowledge the Pathology Core in the San Antonio Nathan Shock Center (P30-AG013319) for the pathological analyses.

Funding

This research was supported by the VA Merit Review grant from the Department of Veteran Affairs (Y.I.), the NIH grant AG13319 (Y.I.), the American Federation for Aging Research (AFAR) grant (Y.I.), and a grant from the Glenn Foundation (Y.I.).

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Authors and Affiliations

  1. Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78245, USA

    Geneva M. Cunningham, Lisa C. Flores, Madeline G. Roman, Christie Cheng, Sara Dube, Colton Allen, Joseph M. Valentine, Gene B. Hubbard & Yuji Ikeno

  2. Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA

    Gene B. Hubbard & Yuji Ikeno

  3. Department of Cell Systems and Anatomy, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA

    Yidong Bai

  4. Transgenic Animal Model Core, University of Michigan, Ann Arbor, MI, 48109, USA

    Thomas L. Saunders

  5. Geriatric Research and Education Clinical Center, Audie L. Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, 78229, USA

    Yuji Ikeno

  6. Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX, 78245-3207, USA

    Yuji Ikeno

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  1. Geneva M. Cunningham
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  2. Lisa C. Flores
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  8. Gene B. Hubbard
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  11. Yuji Ikeno
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Correspondence to Yuji Ikeno.

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Cunningham, G.M., Flores, L.C., Roman, M.G. et al. Thioredoxin overexpression in both the cytosol and mitochondria accelerates age-related disease and shortens lifespan in male C57BL/6 mice. GeroScience 40, 453–468 (2018). https://doi.org/10.1007/s11357-018-0039-6

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  • DOI: https://doi.org/10.1007/s11357-018-0039-6

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