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Intermittent fasting promotes rejuvenation of immunosenescent phenotypes in aged adipose tissue

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Abstract

The aging of white adipose tissue (WAT) involves senescence of adipose stem and progenitor cells (ASPCs) and dysregulation of immune cell populations, serving as a major driver of age-associated adipose dysfunction and metabolic diseases. Conversely, the elimination of senescent ASPCs is associated with improvements in overall health. Intermittent fasting (IF), a dietary intervention that incorporates periodic cycles of fasting and refeeding, has been reported to promote weight loss and fat mass reduction and improve glucose and insulin homeostasis in both murine and human studies. While previous studies have assessed the effects of IF on obesity-associated metabolic dysfunction, few studies have examined the aging-specific changes to ASPCs and immune cell populations in WAT. Here, we show that IF in 18–20-month-old mice reduced senescent phenotypes of ASPCs and restored their adipogenic potential. Intriguingly, IF-treated mice exhibited an increase in adipose eosinophils, which has been reported to be associated with improved WAT homeostasis and immunological fitness in aged mice. The observed cellular and metabolic changes suggest that IF may be a feasible lifestyle regimen to reduce cellular senescence which could result in attenuation of downstream aging-induced WAT dysfunction and metabolic diseases.

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Data Availability

The data that supports the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the Center for Advanced Single Cell Analysis at the Hospital for Sick Children Research Institute for their considerable technical contribution, including optimization of staining and panel design in CyTOF experiments.

Funding

H.-K. S. is supported by grants from Canadian Institute of Health Research (CIHR, PJT-162083), Natural Sciences and Engineering Research Council (NSERC, RGPIN-2016–06610) of Canada, and Sun Life Financial New Investigator Award of Banting & Best Diabetes Centre (BBDC) of University of Toronto. H.-K. S. and J.-R. K. are supported by Korea-Canada Research Fund (2019K1A3A1A74107385), S.-Y. P. and J.-R. K. by the Medical Research Center Program (2022R1A5A2018865), and S.-Y. P. (2019R1A2C1088730) and J.-R. K. (2022R1A2C200409912) by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (J. T. is supported by postdoctoral fellowship of Banting & Best Diabetes Centre (BBDC) of University of Toronto). J. H. L. is supported by Doctoral Program Postgraduate Scholarship (PGS-D) from Natural Sciences and Engineering Research (NSERC).

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Author notes

  1. Kafi N. Ealey and Jacques Togo Contributed Equally.

Authors and Affiliations

  1. Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada

    Kafi N. Ealey, Jacques Togo, Ju Hee Lee, Yash Patel & Hoon-Ki Sung

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Ju Hee Lee & Hoon-Ki Sung

  3. Department of Biochemistry, Yeungnam University, Daegu, 42415, Republic of Korea

    Jae-Ryong Kim

  4. Senotherapy-based Metabolic Disease Control Research Center, Yeungnam University, Daegu, 42415, Republic of Korea

    Jae-Ryong Kim & So-Young Park

  5. Department of Physiology, Yeungnam University, Daegu, 42415, Republic of Korea

    So-Young Park

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  1. Kafi N. Ealey
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Ealey, K.N., Togo, J., Lee, J.H. et al. Intermittent fasting promotes rejuvenation of immunosenescent phenotypes in aged adipose tissue. GeroScience 46, 3457–3470 (2024). https://doi.org/10.1007/s11357-024-01093-4

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