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Effect of Exercise on DNA Methylation Age Acceleration in Breast Cancer Patients Undergoing Aromatase Inhibitor Therapy

Koloskee, Amanda (2023) Effect of Exercise on DNA Methylation Age Acceleration in Breast Cancer Patients Undergoing Aromatase Inhibitor Therapy. Master's Thesis, University of Pittsburgh. (Unpublished)

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Background: Breast cancer patients being treated with aromatase inhibitor (AI) therapy have demonstrated a significant decline in cognitive function, particularly in executive function, working memory, and attention, in previous studies. Cognitive decline has been linked to increased biological aging, often measured through DNA methylation (DNAm) levels. Exercise has been shown to both increase cognitive function and promote healthy forms of DNA methylation. Epigenetic clocks are tools to calculate DNAm age (biological age), and DNAm age acceleration is a measure of the difference between biological and chronological age. A sample of older, post-menopausal female breast cancer patients being treated with aromatase inhibitor (AI) therapy were split into two groups: Exercise Intervention (n = 60) and Usual Care (n = 56). In this blinded randomized control trial, the Exercise Intervention group completed a moderate-intensity exercise regimen for six months. DNAm age estimates were calculated from this sample with Horvath1, PhenoAge, and GrimAge principal component (PC) clocks and a non-PC DNAmFitAge clock. The purpose of this study is to investigate the relationships between DNAm age acceleration, AI therapy, exercise, and cognitive function phenotypes.
Results: Mixed modeling with repeated measures revealed that Horvath1, PhenoAge, and GrimAge DNAm age acceleration significantly declined over the course of the study. Significant improvements in attention, psychomotor speed, executive functioning, and mental flexibility were observed in the overall sample, but no significance was attributed to either DNAm age acceleration or the exercise intervention.
Conclusions: The decline in DNAm age acceleration during the study implies AI therapy may be able to counteract the biological aging effects of cancer. Lack of significant differences between the intervention groups indicates the need for a longer study. This study has public health significance because it increases knowledge on the effects of exercise and stress on aging in a vulnerable and large clinical population.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Koloskee, Amandaakk63@pitt.eduakk63
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeeks, Daniel E.weeks@pitt.eduweeks0000-0001-9410-7228
Committee MemberShaffer, John R.john.r.shaffer@pitt.edujohn.r.shaffer0000-0003-1897-1131
Committee MemberConley, Yvetteyconley@pitt.eduyconley
Date: 11 May 2023
Date Type: Publication
Defense Date: 11 April 2023
Approval Date: 11 May 2023
Submission Date: 26 April 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 61
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: breast cancer aromatase inhibitor therapy AI therapy DNAm age DNAm age acceleration cognitive function exercise intervention aging biological age EPICC
Date Deposited: 11 May 2023 15:51
Last Modified: 11 May 2023 15:51


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