The antimetastatic effects of calorie restriction are negated by voluntary exercise in an aggressive breast cancer mouse model

A Amanda Garrido (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH) E Eva Tamayo-Torres (Department of Physiology, Faculty of Pharmacy, University of Valencia) S Sara Abdo (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health) E Ethan Durham (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health) J Jonathan Hirschenson (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health) H Hikari Tanaka (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health) E Eleonora Duregon (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health) H Hazal Ozturk-Gurgen (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health) M Mounisha Kovour (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health) M Monica Bodogai (Immunoregulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health) A Arya Biragyn (Immunoregulation Section, Laboratory of Immunology and Molecular Biology, National Institute on Aging) S Simonetta Camandola (Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health) N Nathan L. Price (Translational Gerontology Branch, National Institute on Aging) M Michel Bernier (Translational Gerontology Branch and Laboratory of Cardiovascular Sciences, National Institute on Aging, NIH) J Julián Carretero (Department of Physiology, Faculty of Pharmacy, University of Valencia) M María Carmen Gómez-Cabrera (Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable, Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana) R Rafael de Cabo (Translational Gerontology Branch and Laboratory of Cardiovascular Sciences, National Institute on Aging, NIH)

Abstract

The role of lifestyle interventions in treatment success has become essential for nearly every disease. Healthy dietary habits, regular exercise, and stress management are key pillars that can improve quality of life during treatment, as well as delay disease onset and progression. In this study, we focus on the combination of mild calorie restriction (CR) and voluntary exercise as coadjuvants to chemotherapy in the treatment of triple-negative breast cancer using the 4T1 mouse model. In this model, voluntary exercise did not add benefits beyond chemotherapy plus CR in terms of primary tumor size, body composition, or physical performance, while dampening the antimetastatic effect of CR in the lungs of sedentary mice. These findings highlight the challenges of translating results from one preclinical model to another, and ultimately to humans. Diet and exercise type and chemotherapeutic agent influence the outcomes of each type of cancer. More research is needed to determine if and when exercise should be recommended to particular cancer patients.

Article Details

Volume / Issue Vol. 123, Issue 18
Published May 05, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (17)

A

Amanda Garrido

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH

E

Eva Tamayo-Torres

Department of Physiology, Faculty of Pharmacy, University of Valencia

S

Sara Abdo

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health

E

Ethan Durham

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health

J

Jonathan Hirschenson

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health

H

Hikari Tanaka

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health

E

Eleonora Duregon

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health

H

Hazal Ozturk-Gurgen

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health

M

Mounisha Kovour

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health

M

Monica Bodogai

Immunoregulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health

A

Arya Biragyn

Immunoregulation Section, Laboratory of Immunology and Molecular Biology, National Institute on Aging

S

Simonetta Camandola

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health

N

Nathan L. Price

Translational Gerontology Branch, National Institute on Aging

M

Michel Bernier

Translational Gerontology Branch and Laboratory of Cardiovascular Sciences, National Institute on Aging, NIH

J

Julián Carretero

Department of Physiology, Faculty of Pharmacy, University of Valencia

M

María Carmen Gómez-Cabrera

Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable, Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana

R

Rafael de Cabo

Translational Gerontology Branch and Laboratory of Cardiovascular Sciences, National Institute on Aging, NIH