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The effects of exercise and diet on oxidative stress and telomere length in breast cancer survivors

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Abstract

Purpose

Cancer and its treatments accelerate biological aging. This analysis tested the hypothesis that exercise and diet reduce oxidative stress and prevent telomere shortening in breast cancer survivors.

Methods

In a 2 × 2 factorial design, 342 breast cancer survivors who were insufficiently physically active and had overweight or obesity at enrollment were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. The endpoints of this analysis were the change from baseline to week 52 in 8-iso-prostaglandin F2α (8-iso-PGF2α) and lymphocyte telomere length.

Results

Baseline telomere length was shorter than age-adjusted normative values (median difference: − 1.8 kilobases; 95% CI − 2.4, − 1.1); equivalent to 21 years (95% CI 17, 25) of accelerated chronological aging. Compared to control, exercise alone did not change 8-iso-PGF2α [9.9%; 95% confidence interval (CI) − 1.0, 20.8] or telomere length (13.8%; 95% CI − 15.6, 43.3). Compared to control, diet alone was associated with reduced 8-iso-PGF2α (− 10.5%; 95% CI − 19.5, − 1.5) but did not change telomere length (12.1%; 95% CI − 17.2, 41.3). Compared to control, exercise plus diet was associated with reduced 8-iso-PGF2α (− 9.8%; 95% CI − 18.7, − 0.9) but did not change telomere length (− 8.5%; 95% CI − 32.1, 15.2). Change in 8-iso-PGF2α did not correlate with change in telomere length (r = 0.07; 95% CI − 0.07, 0.20).

Conclusion

In breast cancer survivors, diet alone or exercise plus diet were associated with reduced oxidative stress but did not change telomere length. This analysis may inform future trials that aim to optimize healthy aging in cancer survivors.

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Data availability

The data described in this manuscript are available upon submission of a research proposal and approval by the corresponding author.

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Funding

This work was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U54-CA155850, UL1-TR001878, P30-CA016520, P30-CA006927. The content is solely the authors' responsibility and does not necessarily represent the official views of the National Institutes of Health. BSN Medical donated compression garments, and Nutrisystem, Inc. provided discounted meal replacements. We thank Dr. Sue Rutherford Siegel and the Biomarker Core Laboratory in the Department of Biobehavioral Health, Penn State, for telomere length analysis. Analysis of eicosanoids was performed in the Vanderbilt University Eicosanoid Core Laboratory. Dr. Brown is supported by the National Cancer Institute of the National Institutes of Health under Award Numbers R00-CA218603 and R25-CA203650, the National Institute of General Medicine Sciences of the National Institutes of Health under Award Number U54-GM104940, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number P30-DK072476, the Susan G. Komen Foundation, and the American Institute for Cancer Research. Dr. Sturgeon reports receiving grants from the National Institutes of Health. Dr. Sarwer is supported by the National Institute for Diabetes and Digestive and Kidney Disease of the National Institutes of Health under Award Number R01-DK108628. Dr. Sturgeon is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1-TR002014, UL1-TR000003, and KL2-TR002015. The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, LA, USA

    Justin C. Brown

  2. LSU Health Sciences Center New Orleans School of Medicine, 1901 Perdido St, New Orleans, LA, USA

    Justin C. Brown

  3. Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, 533 Bolivar St, New Orleans, LA, USA

    Justin C. Brown

  4. Penn State College of Medicine, 400 University Drive, Hershey, PA, 17033, USA

    Kathleen Sturgeon

  5. Temple University College of Public Health, 1101 W. Montgomery Ave, Philadelphia, PA, USA

    David B. Sarwer

  6. New York University Grossman School of Medicine, 180 Madison Ave, New York, NY, USA

    Andrea B. Troxel

  7. Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, USA

    Angela M. DeMichele

  8. Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, USA

    Crystal S. Denlinger

  9. Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA

    Kathryn H. Schmitz

Authors
  1. Justin C. Brown
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  2. Kathleen Sturgeon
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  7. Kathryn H. Schmitz
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Contributions

Conception and design of study (JCB, DBS, ABT, KS, AMD, CSD, KHS); acquisition of data (JCB, DBS, KS, AMD, CSD, KHS); analysis and/or interpretation of data (JCB, DBS, ABT, KS, KHS); drafting the manuscript (JCB, KHS); approval of the version of the manuscript to be published (JCS, DBS, ABT, KS, AMD, CSD, KHS).

Corresponding author

Correspondence to Kathryn H. Schmitz.

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Conflicts of interest

Dr. Brown reports receiving grants from the National Institutes of Health, the American Institute for Cancer Research, and the Susan G. Komen Foundation. Dr. Sarwer reports receiving grants from the National Institutes of Health and personal fees from Ethicon and Novo Nordisk. Dr. Troxel reports receiving grants from the National Institutes of Health. Dr. DeMichele reports receiving grants from Novartis, Pfizer, Genentech, Calithera, and Menarini. Dr. Denlinger reports honoraria from Zymeworks for data safety and monitoring board committee work. Dr. Schmitz reports receiving grants from the National Institutes of Health, nonfinancial support from BSN Medical, personal fees from Klose Training, and a licensed patent for a Strength After Breast Cancer course. No other disclosures were reported.

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Brown, J.C., Sturgeon, K., Sarwer, D.B. et al. The effects of exercise and diet on oxidative stress and telomere length in breast cancer survivors. Breast Cancer Res Treat 199, 109–117 (2023). https://doi.org/10.1007/s10549-023-06868-5

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