DNA Methylation and Cancer Prevention: Duration and Intensity of Exercise

Specific aim 1. Using a fully crossed 2 (intensity) X 2 (duration) design, the investigators will demonstrate a dose-response relationship between volume of aerobic exercise and changes in DNA methylation over four months among previously sedentary women.

Specific aim 2. There are no published data on the extent to which positive effects of exercise on methylation might decay if exercise is not continued. The investigators will gather data on the natural history of methylation decay after training.

Specific aim 1. Using a fully crossed 2 (intensity) X 2 (duration) design, the investigators will demonstrate a dose-response relationship between volume of aerobic exercise and changes in DNA methylation over four months among previously sedentary women.

* Hypothesis 1: The investigators predict that there will be an interaction between intensity and duration characterized by a dose-dependent response to total exercise volume, such that women will experience the greatest improvements in methylation at high intensity/high duration (16.4 kcal/kg/week) and the least improvements in methylation at low intensity/low duration (5.6 kcal/kg/week).
* Hypothesis 2: The investigators predict that there will be a main effect of exercise duration, such that women exercising for 40 minutes/session, 4 sessions per week will show more improvement in DNA methylation compared with women exercising for 20 minutes/session, 4 sessions per week.
* Hypothesis 3: The investigators predict that there will be a main effect of exercise intensity, such that women exercising at 75% of VO2max will show more improvement in DNA methylation compared with women exercising at 55% of VO2max.

Specific aim 2. There are no published data on the extent to which positive effects of exercise on methylation might decay if exercise is not continued. The investigators will gather data on the natural history of methylation decay after training.

• Hypothesis 4: At six months following the end of supervised exercise, the investigators will assess the influence of the different levels of initial training and the passage of time on DNA methylation, covarying whether or not participants continued to exercise. It is predicted that the highest volume group will show the greatest persistence of positive changes in DNA methylation. Alternatively, it is possible that all four groups will return to baseline methylation levels of methylation, and there will be no difference in methylation at 6 months following the end of supervised exercise.

Eligibility Criteria:
Inclusion Criteria:

* Female
* Age 30-45
* Sedentary (i.e., \< 40 minutes per week of moderate physical activity in the past 6-months; this criterion will be relaxed to \<60 minutes per week if it limits enrollment)
* Menstruating regularly (not amenorrheic or dysmenorrheic)
* Non-smokers
* Willing to accept random assignment to condition
* Willing to provide blood and saliva samples for epigenetic analysis
* Willing to and physically capable of safely engaging in moderate exercise activity (i.e., no injuries, physical impairments, or pre-existing contraindications) as assessed by a study physician
* Able to successfully complete a VO2max test without evidence of cardiac or other abnormalities
* Planning to remain in the Denver metro area for the next 10 months

Exclusion Criteria:

* Have a BMI \> 35kg/m2
* Are diabetic or on a restricted diet
* Have uncontrolled hypertension defined as resting systolic BP \>150 mmHg or diastolic BP\>90 mmHg (to be assessed during physical exam, not on phone screen). (Participants who do not meet these criteria at first screening will be re-evaluated, including after follow-up evaluation by the primary care physician with initiation or adjustment of anti-hypertensive medications)
* Have a cardiovascular or respiratory disease including subjective or objective indicators of ischemic heart disease (e.g., angina, ST segment depression) or serious arrhythmias at rest or during the maximal exercise test (VO2max). (Participants who do not meet these criteria at first screening will be re-evaluated; follow-up evaluation must include diagnostic testing (e.g., thallium stress test) with interpretation by a cardiologist)
* Have a history of breast neoplasia
* Are currently receiving treatment for any type of cancer
* Are on psychotropic medications
* Are currently under treatment for any psychiatric disorder
* Are currently under treatment for alcohol or drug abuse
* Are currently pregnant or attempting to become pregnant in the next 6-months