Cadence and Intensity Across the Adult Lifespan

There will be up to two lab visits for CADENCE-ADULTS participants, all of which will be
completed in the Physical Activity and Health Lab at University of Massachusetts Amherst.
Participation will include: orientation to the experiment, consent, physical examination and
testing. The entire research protocol will last between 3.5-4.5 hrs.

For all participants the first visit will consist of an orientation to the project,
screening, informed consent, physical exam and ECG (if necessary, see below), as well as the
graded treadmill walking protocol.

Pre-visit:

Prior to coming to the laboratory participants will undergo a phone screening in order to
identify interest, outline basic inclusion/exclusion criteria and give a brief description of
the study protocol. If interested participants will be scheduled for their first visit and be
given the instruction to arrive at the laboratory having observed at least a 4-hour fast.

The reason for required fast is that metabolic responses to exercise are affected by food
intake. By fasting for 4 hrs prior to the exercise testing window the investigators insure
standardization of metabolic responses to exercise.

Orientation:

Participants will be taken through a slide orientation session where all aspects of the study
will be covered. This slide set has both written and pictorial descriptions of the different
phases of the experiment, eligibility criteria, participant rights, compensation and
confidentially. At this time participants have the opportunity to ask any questions of the
experimenters that they would like.

Consent:

If after being presented with the orientation information a person would like to enroll in
the study they will be given the informed consent document. They will be given ample
opportunity to read through the document and decide if they would like to sign the paper and
enroll in the study.

Pre-testing screening:

Once the consent paperwork is signed participants will have their height, seating height,
body weight, body fat percentage, BMI, and waist circumference taken. Questions will also be
asked to ascertain date of birth, gender and race/ethnicity. Participants will then be taken
through a series of screening questionnaires to assess cardio-metabolic risk via the the most
recent edition of the American College of Sports Medicine (ACSM) Resource for The Health
Fitness Specialist and also the American heart Association's (AHA) risk stratification
recommendations presented in the same ACSM resource. Risk will be assessed in the following
ways:

For participants considered low risk (men 21-44 years of age and women 21-54 years of age,
asymptomatic and with ≤ 1 risk factors) no physical examination and resting ECG is necessary
prior to enrolling in the study. Those considered at moderate risk (men 45-69 and women 55-69
years of age, asymptomatic with ≥ 2 risk factors) will require the physical examination and
resting ECG prior to enrolling in the study. Those considered to be high risk (symptomatic,
or with known cardiac, pulmonary or metabolic disease), or found to be at high risk following
risk stratification, will require medical supervision during the submaximal treadmill
exercise protocol.

All participants who are 61-85 years of age will require a physical examination and resting
ECG prior to enrolling.

Physical Exam and ECG:

A physical exam will be conducted by our study staff under the guidance of our medical
examiner (Dr. Chipkin) to assess for medical conditions that may interfere with exercise
protocol. In addition, this is being performed to ensure participant safety during exercise
protocol .

Electrocardiogram (ECG). A 12-lead electrocardiogram will be performed by study staff and
reviewed by a clinical exercise specialist (e.g., clinical exercise physiologist) or MD prior
to exercise protocol.

All testing will be overseen by trained study staff with an MS or PhD in Exercise
Science/Physiology or BS in Kinesiology. These accommodations meet the latest ACSM (10
Edition, Guidelines for Exercise Testing and Prescription) and AHA criteria for exercise
protocols.

Experimental Testing:

Immediately prior to exercise testing participants will be outfitted with a number of
non-invasive devices to measure/monitor physical activity. Additionally they will be
outfitted with a wireless metabolic mask to measure gas exchange for a criterion measure of
energy expenditure.

Participants will complete both the treadmill testing and mock free-living activities while
physical activity and oxygen uptake are continually and concurrently measured.

Each speed on the treadmill and each free-living activity will be performed for 5 minutes
with a 2 minute rest between each activity. Participants will complete each activity at their
preferred level of effort.

Treadmill walking:

Participants will then complete a series of walking bouts on a treadmill while their physical
activity and oxygen uptake are concurrently assessed. The walking bouts start at 0.5 miles
per hour and end at 6 miles per hour (0.5 miles per hour increments). Treadmill testing will
be terminated when any of the following criteria are attained: upon any natural tendency to
reach out to use the hand rails to steady and/or support themselves, following completion of
the fist bout when their heart rate attains 75% of age-predicted maximum heart
rate(indicative of having achieved vigorous intensity), participants identify as having a
14/20 or greater level of exertion on a Borg Rate of Perceived Exertion Scale, following
completion of first bout when the participant naturally selects to run instead of walk,
following completion of a bout at 6.0 mph, or before any of the above criteria, as the
participant prefers, reflecting their personal tolerance.

Free-Living Activities:

Participants will rest in chair, watch a portion of a movie while seated in a chair, complete
seated computer work, walk up and down a set of stairs, fold laundry while standing, and
vacuum the floor. Participant will then complete a continuous walk for 5 minutes at their
desired pace. This walk will be completed in a corridor with an electronic gait mat
(GaitRite, Inc., USA) covering a portion of the walking course.

Following completion of the testing, participants will be given a small snack and drink and
will be monitored to ensure it is safe for them to return to their day.

NIH NIA supplement award R01AG049024-05S1, start date May 2018 -

In addition to the above procedures related to the CADENCE-Adults parent award, participants
aged 61-85 may also participate in an optional component of the study related to the
supplement award. This will include:

1 week of physical activity monitoring: An additional 7 consecutive days of physical activity
monitoring (ActiGraph GT9X and New Lifestyle DigiWalker SW-200). Participants will wear the
devices on their waist for 24 hours a day and maintain their usual physical activity levels.
They will also be asked to complete a daily physical activity log. Participants will be to
complete this within twelve weeks of their final visit to the physical activity and health
lab. In addition, they will also be asked a series questions regarding their physical
activity history over the past month (CHAMPS questionnaire).

AND Peak aerobic fitness treadmill protocol (modified Balke protocol). Participants will will
first walk for a warm-up period of 6 - 10 minutes at a comfortable walking speed. Treadmill
speed will then be set to elicit 70-80% of their age-predicted max heart-rate (HRmax), and
remain constant for the entirety of the protocol. This speed will be determined based on the
speed and heart rate relationship observed during the previous treadmill test (sub-maximal
treadmill protocol). Specifically, if 70% of HRmax was reached during the previous test, the
peak aerobic fitness test will start at the first speed at which this heart rate threshold
was first observed. If the previous test was terminated before 70% of HRmax (e.g., the
participant naturally chose to run or achieved a rating perceived exertion consistent with a
vigorous intensity), the speed for the peak protocol will be set at 0.5 mph faster than the
previous test's termination speed. If the previous test was terminated before 70% of HRmax
was reached because the participant: indicated they wished to stop the test, the researchers
stopped the test due to safety concerns, they reached for the handrail or became unsteady, or
they achieved a systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg; then
the speed for the peak protocol will be set 0.5 mph slower than the previous termination
speed.

Participant will first walk at the pre-determined testing speed for 2 minutes at a grade
(incline) of 0%. The grade will then be increased from 0% to 4% after 2-minutes, then to 6%
after 4 minutes, and then by 2% every minute thereafter until they indicate that they want to
stop (voluntary exhaustion), or earlier for any safety-related reasons. During this testing,
the participant will be outfitted with the Oxycon Mobile to assess peak aerobic fitness.

For safety reasons, participants will be required to wear the ECG and BP equipment to monitor
their cardiovascular responses during this test. A trained staff member will be on hand to
operate this equipment, monitor responses and ensure safety procedures are followed. Our
medical investigator, Dr Stuart Chipkin will be on hand to supervise all peak treadmill
protocols.

Participants will be required to complete this a minimum of 7 days, and maximum of 12 weeks
from the the submaximal treadmil protocol in the parent award.

Inclusion Criteria:

- Adults between ages 21-85 years, able to ambulate on a treadmill (self-report)

Exclusion Criteria:

- BMI less than 18.5 or more than 40kg/m^2

- Having smoked tobacco within the past 6 months

- wheelchair bound, or conditions that prevent normal ambulation

- Resting systolic blood pressure > 159 mm HG, or diastolic blood pressure > 99 mm HG

- Hospitalization for mental illness within the past 5 years (for the 41-60 and 61-85
year old cohorts this was change to "within the past 1 year").

- Any condition/medication that may affect heart rate response to exercise testing.

- Previous history of, or clinical symptoms or signs of, cardiovascular disease, stroke
or transient ischemic attacks, chest pain, unusual dyspnea during physical
activity/exercise, severe ankle swelling, or leg pain while walking.

- Any significant medical condition that may interfere with the study.

- Previous history of musculoskeletal injuries or problems causing severe pain during
physical activity or exercise which interferes with daily activities.

- Participant has a pacemaker or other implanted medical device (including metal joint
replacements).

- Participant is pregnant.

- Participant is unable to complete all testing (1 or two sessions, based on risk
factors) within a maximal two week period.

- Individuals wearing a full beard may need to be excluded from the study, as large
amounts of facial hair around the mouth and nose interfere with the seal of the device
that measures the air you breath. Because of this we are seeking participants that are
clean-shaven or with a beard where areas around the nose and mouth are clean-shaven
(e.g. goatee).