Aging and the Mitochondrial Response to Exercise Training, Measured by Noninvasive 31P Magnetic Resonance Spectroscopy

Inclusion Criteria: ADULT PARTICIPANT INCLUSION CRITERIA - YOUNG PARTICIPANTS * Willingness to provide informed consent to participate in the MoTrMito Study * Must be able to read and speak English well enough to provide informed consent and understand instructions * Aged 18 - 39 y * Body Mass Index (BMI) \>19 to \<35 kg/m2 ADULT PARTICIPANT INCLUSION CRITERIA - MIDDLE AGE PARTICIPANTS * Willingness to provide informed consent to participate in the MoTrMito Study * Must be able to read and speak English well enough to provide informed consent and understand instructions * Aged 40 - 59 y * Body Mass Index (BMI) \>19 to \<35 kg/m2 ADULT PARTICIPANT INCLUSION CRITERIA - OLD AGE PARTICIPANTS * Willingness to provide informed consent to participate in the MoTrMito Study * Must be able to read and speak English well enough to provide informed consent and understand instructions * Aged \>=60 y * Body Mass Index (BMI) \>19 to \<35 kg/m2 Exclusion Criteria: ADULT PARTICIPANT EXCLUSION CRITERIA * Exclusion criteria are confirmed by either self-report (i.e., medical and medication histories reviewed by a clinician), screening tests performed by the MoTrMito study team at each clinical site, and/or clinician judgement as specified for each criterion. 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) * History of a bleeding disorder or clotting abnormality 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) * Clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD) 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) * Supplemental, replacement or therapeutic use of estrogens or progestins within the last 6 months, other than birth control or to control menopausal symptoms 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) \>2 times the laboratory upper limit of normal * 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) * Individuals receiving any active treatment (including monoclonal antibodies) within the last 6 months 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) * Self-reported use ≥3 days/week of tobacco or e-cigarette/e-nicotine products Marijuana (self-report) * Self-reported use ≥3 days/week in any form Shift workers (self-report) * Night shift work in the last 6 months * Planning night shift work during the study period Cognitive status (screening) * Unable to give consent to participate in and safely complete the protocol, as based on the judgement of the local investigator 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) * Known allergy to lidocaine or other local anesthetic 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 EXCLUSIONS FOR MEDICATION USE * 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 * Methacarbamol; cyclobenzaprine; tizanidine; baclofen 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