To test the hypothesis that home-based leg heat therapy improves functional capacity, vascular function, and exercise hyperemia in older adults.

Chronic whole-body heating (i.e., heat therapy) has gained attention as a novel strategy to improve clinical and physiological outcomes in a number of populations. However, whole-body heat therapy is quite uncomfortable and may require trained personnel to ensure participant safety, especially for those more at risk for heat-related illness. Moreover, the applicability and acceptability of whole-body heat therapy are questionable as equipment cost is substantial and adherence will be low if individuals are required to travel if they cannot afford in-home therapy. Home-based leg heat therapy offers an opportunity to leverage the demonstrated benefits of whole-body heat therapy while managing safety and convenience.

The hypothesis will be addressed in the following Specific Aims:

Aim 1: Determine the extent to which home-based leg heat therapy improves functional capacity in older adults. Functional capacity will be assessed before and after heat therapy or sham intervention via the 6-min walk test and the Short Physical Performance Battery.

Aim 2: Determine if home-based leg heat therapy improves vascular function and exercise hyperemia in the older adults of Aim 1. Using state-of-the-art techniques of skeletal muscle microdialysis and high-resolution duplex ultrasound, the investigators will pharmacodissect mechanisms of vascular function and exercise hyperemia before and after each intervention. The outcomes of Aim 2, while providing insight into the mechanisms whereby heat therapy improves functional capacity, should be considered independent of the outcomes of Aim 1 given that vascular health is a key independent, yet modifiable risk factor for cardiovascular morbidity and mortality.

Inclusion Criteria:

1. 55 to 80 years of age
2. No tobacco/nicotine use within preceding 6 months (e.g., cigarettes, chewing tobacco, nicotine gum or patches, and vapor smoking)
3. Systolic blood pressure <140 mmHg; diastolic blood pressure <90 mmHg
4. Normal 12-lead ECG (reviewed by a physician)
5. Normal clinical results from a medical exam reviewed by a board-certified physician (e.g., General Health Questionnaire - see attached document)
6. Body mass index (BMI) <40 unless athletic/muscular build; calculation = body weight (kg)/height (m2)
7. Females Only: Post-menopausal

Exclusion Criteria:

1. Not meeting the age criteria
2. Body mass index (BMI) >40 unless athletic/muscular build; calculation = body weight (kg)/height (m2)
3. Use of tobacco or nicotine products within the last 6 months (tobacco cigarettes, chewing tobacco, nicotine patches or gum)
4. Not abstaining from the following 24 hours prior to the experimental session: exercise, alcoholic substances, prescription or non-prescription medications (unless cleared by the medical screener), dietary supplements, herbal medications, caffeinated substances (including chocolate, coffee, tea (iced or hot), caffeinated energy drinks, and sodas)
5. S who weigh less than 80 lbs
6. Use of prescription drugs, non-prescription drugs or herbal medicines known to alter vascular function unless cleared prior to the study
7. Use of anti-hypertensive medications
8. Use of beta blockers
9. Daily use of bronchodilators
10. Current use of anti-coagulant therapy
11. Current use of hormone replacement therapy (e.g., estrogen, testosterone)
12. Current diagnosis of cancer
13. Signs of overt cardio-metabolic abnormalities (e.g., uncontrolled diabetes - HbA1c >7.5, a resting systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg; abnormal 12-lead ECG)
14. History of cerebrovascular abnormalities (e.g., prior stroke, transient ischemic attacks, epilepsy, increased intracranial pressure)
15. Known history of atherosclerosis (i.e., plaque formation)
16. Autonomic dysfunction (e.g., Shy-Drager Syndrome, Bradbury-Eggleston syndrome, idiopathic orthostatic hypotension)
17. Respiratory illnesses (e.g., chronic asthma (including exercise-induced asthma), Chronic Obstructive Pulmonary Disease, Reactive Airway Disease). Note: subjects with exercised-induced asthma or who have had COVID-19 will be allowed to participate
18. History of anaphylaxis
19. Severe phobia of needles
20. History of alcohol or drug abuse which inhibits the participants ability to complete this study
21. Latex allergy
22. Known allergies or sensitivities to drugs used in the study (e.g., Lidocaine HCL, acetylcholine HCL, methacholine chloride, sodium nitroprusside, nitroglycerin, or related drugs)
23. Implanted electronic medical devices (e.g. cardiac pacemaker)
24. Tissue or skin abnormalities of the legs (e.g., infection, injury, open wound, ischemic tissue, phlebitis, active bleeding, neuropathy)
25. Tissue or skin abnormalities of the arm (e.g., unhealed or open wound or circulatory deficits)
26. Current Fever (oral temp >99.5 °F/ 37.5 °C) aa) Current use of PDE3 inhibitors (e.g., Viagra) or soluble guanylate cyclase (sGC) stimulators (e.g., riociguat), or unwillingness to withhold medication for 2 weeks prior to laboratory testing bb) Diagnosis of neurological disease or cognitive dysfunction cc) Cardiac surgery or cardiac events (e.g., coronary artery bypass graft surgery, myocardial infarction, heart failure) dd) Abnormal clotting, clots in deep veins in the legs or pelvis, or blood clots to the lungs ee) Individuals who have had mastectomies ff) History of methemoglobinemia

With the exception of a research nurse, all research personnel are blinded.