Investigating the Effects of Aerobic and Resistance Training in Vivo on Skeletal Muscle Metabolism in Vitro in Primary Human Muscle Cells (MoTrMyo)

Eligibility Criteria

• * Willingness to provide informed consent to participate in the MoTrPAC Study
• * Must be able to read and speak English well enough to provide informed consent and understand instructions
• * Aged ≥18 y
• * Body Mass Index (BMI) \>19 to \<35 kg/m2
• * Sedentary defined as self-reporting no more than 1 day per week, lasting no more than 60 minutes, of regular (structured) EE \[e.g., brisk walking, jogging, running, cycling, elliptical, or swimming activity that results in feelings of increased heart rate, rapid breathing, and/or sweating\] or RE (resulting in muscular fatigue) in the past year
• * Persons bicycling as a mode of transportation to and from work \>1 day/week etc. are not considered sedentary
• * Leisure walkers are included unless they meet the heart rate, breathing, and sweating criteria noted above
• * Willingness to provide informed consent to participate in the MoTrPAC Study
• * Must be able to read and speak English well enough to provide informed consent and understand instructions
• * Aged ≥18 y
• * BMI \>19 to \<35 kg/m2
• * Comparator Participants
• * Highly Active Endurance Exercise (HAEE): defined as \>240 minutes/week of ET for \>1 year; this can include running, walking (brisk, power), cycling, elliptical, etc. which (at a minimum) results in increased heart rate, rapid breathing and sweating
• * Must include cycling at least 2 days/week
• * Highly Active Resistance Exercise (HARE): defined as RT of ≥3 upper and ≥3 lower body muscle groups ≥2 times/week for \>1 year; using a prescription sufficient to increase strength and muscle mass
• * Elite or Competitive Athletes: can be included, if they meet HAEE or HARE inclusion criteria
• * Potential participants are informed that use of performance enhancing drugs in the last 6 months is exclusionary
• * In addition to meeting HAEE or HARE inclusion criteria, all HA participants must meet all other exclusion criteria defined in this protocol
• * Individuals who meet inclusion criteria for both HAEE and HARE are exclude
• * Diabetes (self-report and screening tests)
• * Treatment with any hypoglycemic agents (self-report) or A1c \>6.4 (screening test; may reassess once if 6.5-6.7)
• * Fasting glucose \>125 (screening test; may reassess once)
• * Use of hypoglycemic drugs (e.g., metformin) for non-diabetic reasons (self-report)
• * Abnormal bleeding or coagulopathy (self-report)
• * Thyroid disease (screening test)
• * Thyroid Stimulating Hormone (TSH) value outside of the normal range for the laboratory
• * Individuals with hypothyroidism may be referred to their primary care provider (PCP) for evaluation and retested; any medication change must be stable for ≥3 months prior to retesting
• * Individuals with hyperthyroidism are excluded, including those with normal TSH on pharmacologic treatment
• * Pulmonary (self-report)
• * Metabolic bone disease (self-report)
• * History of non-traumatic fracture from a standing height or less
• * Current pharmacologic treatment for low bone mass or osteoporosis, other than calcium, vitamin D, or estrogen
• * Estrogens, progestins (self-report)
• * Pregnancy (screening test) and pregnancy-related conditions (self-report)
• * Pregnant - pregnancy test performed on day of DXA scan in women of child-bearing potential
• * Post-partum during the last 12 months
• * Lactating during the last 12 months
• * Planning to become pregnant during the participation period
• * Elevated blood pressure readings (screening test)
• * Aged \<60 years: Resting Systolic Blood Pressure (SBP) ≥140 mmHg or Resting Diastolic Blood Pressure (DBP) ≥90 mmHg
• * Aged ≥60 years: Resting SBP ≥150 mmHg or Resting DBP ≥90 mmHg
• * Reassessment of BP during screening will be allowed to ensure rested values are obtained
• * Cardiovascular (self-report, screening test, and clinician judgement)
• * Congestive heart failure, coronary artery disease, significant valvular disease, congenital heart disease, serious arrhythmia, stroke, or symptomatic peripheral artery disease (self-report, screening test)
• * Specific criteria used to determine whether a volunteer can undergo the screening Cardiopulmonary Exercise Test (CPET) follow the American Heart Association (AHA) Criteria \[54\]
• * Inability to complete the CPET
• * Abnormal blood lipid profile (screening test)
• * Fasting triglycerides \>500 mg/dL
• * Low-density lipoprotein cholesterol (LDL-C) \>190mg/dL
• * Cancer (self-report)
• * History of cancer treatment (other than non-melanoma skin cancer) and not "cancer-free" for at least 2 years
• * Anti-hormonal therapy (e.g., for breast or prostate cancer) within the last 6 months
• * Chronic infection (self-report)
• * Infections requiring chronic antibiotic or anti-viral treatment
• * Human Immunodeficiency Virus
• * Individuals successfully treated for hepatitis C and virologically negative for at least 6 months are not excluded
• * Liver enzyme tests (Alanine transaminase, Aspartate transaminase) (screening test)
• * Reassessment during screening may be allowed under some conditions (e.g., recent use of acetaminophen)
• * Individuals may be referred to their PCP for evaluation; any medication change must be stable for ≥3 months prior to retesting
• * Chronic renal insufficiency (screening test)
• * Estimated glomerular filtration rate \<60 mL/min/1.73 m2 from serum creatinine (mg/dL) by the Chronic Kidney Disease Epidemiology Collaboration equation
• * Reassessment may be allowed under some conditions (e.g., questionable hydration status or other acute renal insult)
• * Hematocrit (screening test)
• * Hematocrit \>3 points outside of the local normal laboratory ranges for women and men
• * Reassessment may be allowed under certain conditions
• * Individuals may be referred to their PCP for evaluation; any medication change must be stable for ≥3 months prior to retesting
• * Individuals with known thalassemia trait may be included (despite having \>3 points outside of the local normal laboratory ranges), upon approval from their PCP or a hematologist
• * Blood donation (self-report)
• * Whole blood donation in the last 3 months or plans for blood donation during the entire protocol period
• * Platelet or plasma donation in the last week or plans for platelet or plasma donation during the entire protocol period
• * Autoimmune disorders (self-report)
• * Alcohol consumption (self-report)
• * More than 7 drinks per week for women
• * More than 14 drinks per week for men
• * History of binge drinking (≥5 drinks for males or ≥4 drinks for females in a 2-hour period more than once per month)
• * Tobacco (self-report)
• * Marijuana (self-report)
• * Shift workers (self-report)
• * Night shift work in the last 6 months
• * Planning night shift work during the study period
• * Cognitive status (screening)
• * Psychiatric illness (self-report and screening test)
• * Hospitalization for any psychiatric condition within one year (self-report)
• * Center for Epidemiological Studies-Depression Scale (CESD) score ≥16 \[55\] (screening test)
• * Weight change (self-report)
• * Weight change (intentional or not) over the last 6 months of \>5% of body weight
• * Plan to lose or gain weight during the study
• * Lidocaine or other local anesthetic (self-report)
• * Other (clinician judgement)
• * Any other cardiovascular, pulmonary, orthopedic, neurologic, psychiatric or other conditions that, in the opinion of the local clinician, would preclude participation and successful completion of the protocol
• * Any other illnesses that, in the opinion of the local clinician, would negatively impact or mitigate participation in and completion of the protocol
• * Use of any new drug in the last 3 months
• * Dose change for any drug in the last within 3 months
• * Cardiovascular
• * Beta blockers and centrally acting anti-hypertensive drugs (clonidine, guanfacine and alpha-methyl-dopa)
• * Anticoagulants (coumadin or Direct Oral Anticoagulants)
• * Antiarrhythmic drugs: amiodarone, dronaderone, profafenone, disopyrimide, quinidine
• * Antiplatelet drugs (other than aspirin ≥100 mg/day): dipyridamole, clopidogrel, ticagrelor
• * Lipid-lowering medications
• * Participants who volunteer to stop lipid-lowering medications for the duration of the study are allowed; inclusion requires lipid-lowering medication to be stopped for 3 months and participant re-evaluated for LDL-C eligibility
• * Psychiatric drugs
• * Chronic use of medium or long-acting sedatives and hypnotics (short-acting non-benzodiazepine sedative-hypnotics are allowed)
• * All benzodiazepines
• * Tricyclic antidepressants at a dose ≥75 mg total dose per day
• * Two or more drugs for depression
• * Mood stabilizers
• * Antiepileptic drugs
• * Stimulants, Attention-Deficit/Hyperactivity Disorder (ADHD) drugs
• * Muscle relaxants
• * Pulmonary, inflammation
• * Chronic oral steroids
• * Burst/taper oral steroids more than once in the last 12 months
• * B2-agonists
• * allowed if on stable dose at least 3 months
• * Genitourinary
• * Finasteride or dutasteride
• * Daily phosphodiesterase type 5 inhibitor use
• * Hormonal
• * Testosterone, dehydroepiandrosterone, anabolic steroids
• * Anti-estrogens, anti-androgens
• * Growth hormone, insulin like growth factor-I, growth hormone releasing hormone
• * Any drugs used to treat diabetes mellitus or to lower blood glucose
• * Metformin for any indication
• * Any drugs used specifically to induce weight loss
• * Any drugs used specifically to induce muscle growth/hypertrophy or augment exercise-induced muscle hypertrophy
• * Pain/inflammation
• * Narcotics and narcotic receptor agonists
• * Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen ≥3 days per week
• * Other
• * Anti-malarials
• * Low-potency topical steroids if ≥10% of surface area using rule of 9s
• * Any other medications that, in the opinion of local clinicians, would negatively impact or mitigate full participation and completion