Behavioural Experimental: guidelines-based physical activity:

Through a combination of exercise trainer-led in-person and virtual sessions, as well as counselling for independent aerobic exercise, participants will be guided to achieve 150 weekly minutes of moderate-intensity aerobic activity and twice weekly whole-body muscle strengthening.

Behavioural Experimental: guidelines-based healthy eating:

One-on-one phone/virtual counselling from a registered dietitian to change dietary habits to be in line with Canada's Food Guide.

Twice weekly virtual instructor-led whole-body stretching.

Calculated using a widely-used standardized scoring system

Measured during submaximal and maximal periods of a cycling exercise test, using echocardiography.

Measured during rest, submaximal and maximal periods of cycling exercise test, using echocardiography

Measured via echocardiography at rest

Measured using two methods: (1) calculated as the volume of oxygen (VO2) from the corresponding workload from the day 1 treadmill test divided by cardiac output at rest, submaximal, and maximal periods of the cycling exercise test; and (2) direct assessment using near-infrared spectroscopy as a measure of tissue oxygenation in the legs at rest, submaximal, and maximal periods of the cycling exercise test.

Measured using a brachial artery flow-mediated dilation test using ultrasound.

Measured using a common carotid artery image using ultrasound.

Measured as the pulse wave velocity of the central (carotid-femoral) and peripheral leg (femoral-dorsalis pedis) and arm (carotid-radial) regions. Blood pressure may be added as covariate in analysis of arterial stiffness.

Measured as the average of the last 5 of 6 blood pressure measurements using an automatic blood pressure device.

Assessed using a 3-lead electrocardiogram in the supine position for 10 minutes after a 5-minute supine rest.

Measured as thigh muscle fat fraction (percent of muscle compartment composed of fat pixels) determined from contiguous axial fat-water separation 3 Tesla (3T) magnetic resonance images of both thighs.

Measured using an isokinetic dynamometer (Biodex) to assess peak torque and total work in 30 repetitions of knee flexion.

Measured determined from contiguous axial fat-water separation 3T magnetic resonance images of both thighs

Measured via western blotting from a skeletal muscle biopsy of the vastus lateralis muscle. Proteins of interest include those found in mitochondria, contractile signaling pathways, insulin signaling pathways, and in glucose and fat metabolism.

Measured via immunofluorescence from a skeletal muscle biopsy of the vastus lateralis muscle. Outcomes of interest include skeletal muscle capillarization, lipid content, and fiber type and cross sectional area.

Measured via spectrophotometer to assess the maximal enzyme activity of enzymes involved in skeletal muscle oxidative capacity, from a biopsy of the vastus lateralis muscle.

Measured using a body composition device (BodPod) to estimate whole body fat (in kg and %) and fat free mass (in kg and %).

Volumes of adipose tissue in the visceral region measured using 3T fat-water separation magnetic resonance imaging

Measured as percent of liver volume composed of fat pixels determined from 3 slices through the middle of the liver using the PROFIT1 3T magnetic resonance images sequence.

Circumferences of the waist, hip and neck, measured using an inelastic tape

Assessments from blood including leptin, adiponectin, Tumour Necrosis Factor alpha (TNF-a), Interleukin-6 (IL-6), C-reactive protein (CRP). These measures have been grouped together as the markers will be considered together when interpreted.

Analyzed from blood serum using a clinical assay at a core lab.

Analyzed from blood plasma using a clinical assay at a core lab.

Various components of dietary intake including macronutrients and micronutrients will be assessed through 3-day food records over 2 weekdays and 1 weekend collected using Automated Self-Administered 24hour (ASA-24) online system.

Assessment of ALT, AST, and albumin via a fasting blood serum draw, analyzed on a clinical assay at a core lab.

Liver T1 time evaluated using the PROFIT1 magnetic resonance sequence, validated marker of liver fibrosis.

Average adherence to prescribed aerobic physical activity weekly minutes measured via Garmin smart watch

Average adherence to prescribed resistance exercise activity weekly sessions via an attendance log

An overall measure of alignment with the dietary guidelines measured via the Canadian healthy eating index calculated from 3-day diet records

Assessed by RAND-36, where an independent score is provided for 8 scales ranging from 0 to 100 and 2 component summary scales ranging from 0-50 with a higher score indicating better quality of life.

Assessed by the Menopause-specific Quality of Life (MENQOL) questionnaire. Each of four domains is constrained between 1 to 8 where a higher score indicates more symptoms.

Assessed by the perceived stress scale (PSS-14) where individual scores can range from 0 to 56 with higher scores indicating higher perceived stress

Measured by the Hospital Anxiety and Depression Scale (HADS); score ranges from 0-21 for each of depression and anxiety with a higher score indicating more severe depression or anxiety

Assessed by the barriers to self-efficacy scale (BARSE). For each item, participants indicate their confidence to execute the behavior on a 100-point percentage scale comprised of 10-point increments, ranging from 0% (not at all confident) to 100% (highly confident). Total strength for each measure of self-efficacy is then calculated by summing the confidence ratings and dividing by the total number of items in the scale, resulting in a maximum possible efficacy score of 100.

Assessed via the multi-process action control approach, which is a series of questionnaires developed to understand affective attitudes, instrumental attitudes, perceived capability over physical activity, perceived opportunity for physical activity, decisional intentions, behavioural regulation, physical activity habits, and identity around physical activity. Higher scores represent better physical activity motivations. (Reference: Rhodes, R.E. (2017). The evolving understanding of physical activity behavior: A multi-process action control approach. In A. J. Elliot (Ed), Advances in Motivation Science. (pp. 171-205).)

Subjectively assessed by the Pittsburgh Sleep Quality Index (PQSI), which measures components of sleep: sleep duration, disturbance, sleep latency, daytime dysfunction due to sleepiness, sleep efficiency, overall sleep quality, and sleep medication use, with higher scores reflecting poorer sleep quality.

Measured via Garmin smart watch for the total sleep duration and efficiency.

Assessed by the Recent Physical Activity Questionnaire (RPAQ) that collects information about types and amounts of activity (sedentary and physical activities) over the last 3 months in the following domains: leisure time, occupation, commuting, domestic life, with greater scores indicating longer time engaging in forms of activity.

Assessed using fasting blood serum in a clinical assay.

Assessed using a salivary sample in-house using a clinical assay.

Assessed using a fasting blood plasma sample in a clinical assay at a core lab.

Assessed using fasting blood serum in a clinical assay.

Assessed using a calibrated scale attached to the BodPod body composition device.

Calculated from a measurement of height using a stadiometer and body weight (detailed above).

Energy balance will be quantified as: 3-day avg calorie intake - [estimated resting metabolic rate + 3-day avg Garmin estimate of physical activity energy expenditure + 10% of calorie intake (thermic effect of food)].