Heat and Exercise in Aging as Therapy (HEAT)

To achieve the study objectives, researchers will first compare the outcomes of local heat therapy to: 1) HIIT and 2) heat pads set to maintain normal skeletal muscle temperature (control group). Then, researchers will compare the outcomes of the local heat therapy and control groups after a subsequent HIIT intervention. This will enable the researchers to assess the effectiveness of local heat therapy (compared to HIIT and preceding HIIT) to improve skeletal muscle health, physical function, blood sugar control.

Study Procedures:

All participants will visit the laboratory over three days at the start of the study for baseline assessments and sample collection.

Participants in the Control (CON) and Local Heat Therapy (LHT) groups will:

Phase 1:

* Use heat pads on both thighs at a pre-determined temperature for 90 minutes daily, 6 days a week (5 days at home and 1 day in the laboratory; 12 laboratory visits) for the first 12 weeks.
* Maintain a log of each heat pad session.
* Visit the laboratory over three days at the end of Phase 1 for follow-up assessments and sample collection.

Phase 2:

* Visit the laboratory three days per week for 12 weeks (a total of 36 visits) for exercise training.
* Visit the laboratory over three days at the end of Phase 2 for final assessments and sample collection.

Participants in the HIIT Group will:

Phase 1:

* Visit the laboratory three days per week for 12 weeks (a total of 36 visits) for exercise training.
* Visit the laboratory over three days at the end of Phase 1 for final assessments and sample collection.

• Heat therapy (Behavioral): Heat pads will be set to a pre-determined, optimized temperature and applied to both legs for 90 min, 6d/wk (5 at-home and 1 in-lab).
• High-intensity interval training (Behavioral): High-intensity interval training will be performed 3 days per week for 12 weeks.

Primary outcomes

• Glycemic control [Before intervention, after Phase 1 (at about 12 weeks), and after Phase 2 (at about 24 weeks, except HIIT group)]: Oral glucose tolerance test (OGTT)
• Skeletal muscle architecture 1 [Before intervention, after Phase 1 (at about 12 weeks), and after Phase 2 (at about 24 weeks, except HIIT group)]: Immunohistochemical assessment of muscle fiber cross-sectional area and capillary density
• Skeletal muscle architecture 2 [Before intervention, after Phase 1 (at about 12 weeks), and after Phase 2 (at about 24 weeks, except HIIT group)]: Assessment of skeletal muscle mitochondrial content
• Frailty status [Before intervention, after Phase 1 (at about 12 weeks), and after Phase 2 (at about 24 weeks, except HIIT group)]: Fried's Phenotypic Frailty assessment
• Exercise capacity [Before intervention, after Phase 1 (at about 12 weeks), and after Phase 2 (at about 24 weeks, except HIIT group)]: VO2peak testing

Secondary outcomes

• Anthropometrics 1 [Weekly for about 14 (HIIT group) or about 27 (LHT and CON groups) weeks]: Body mass and height to calculate body mass index (BMI)
• Anthropometrics 2 [Weekly for about 14 (HIIT group) or about 27 (LHT and CON groups) weeks]: Waist-to-hip ratio
• Body composition [Before intervention, after Phase 1 (at about 12 weeks), and after Phase 2 (at about 24 weeks, except HIIT group)]: Lean versus fat mass assessed by dual-energy x-ray absorptiometry (DEXA)
• Sleep quality [Weekly for about 14 (HIIT group) or about 27 (LHT and CON groups) weeks]: 7-point likert scale

Sex: All, ages: 50 Years to any

Inclusion Criteria:

* Age ≥ 50 years
* Women who are postmenopausal, defined as no menstrual period for at least 12 consecutive months.
* Sedentary (structured exercise <30 minutes, 3x/week)
* Body weight is at least 110 lbs
* Meet criteria for prediabetes (fasting blood glucose 100-125 mg/dl, hemoglobin A1c 5.7-6.4%)
* Consume <8 (women) or <15 (men) alcohol-containing beverages per week
* Do not use nicotine or cannabis
* Not taking any medications that could interfere with responses to the interventions (e.g., corticosteroids, opiates, benzodiazepines, tricyclic antidepressants, beta blockers, sulfonylureas, insulin, metformin, anticoagulants, barbiturates, insulin sensitizers, fibrates, immunosuppressants). If you don't know, that's okay. We'll ask what medications you are on and check whether they fall into one of these categories.

Exclusion Criteria:

* History of peripheral neuropathies
* Currently taking prescription blood thinners
* Medical complications that could would contraindicate participation in the high intensity interval training (HIIT) intervention including: orthopedic complications that would limit your ability to perform cycling exercise, significant cardiovascular impairments (e.g., history of arrhythmias, severe uncontrolled hypertension, etc.), diagnosed metabolic disease (e.g., diabetes), renal disease, sickle cell anemia, or cancer in remission for <6 months.
* Known history of slow wound healing
* Lidocaine allergy
* Latex allergy
* Currently pregnant
* >1.5" subcutaneous fat over the thigh muscle
* Symptoms suggestive of cardiovascular, respiratory, metabolic, or renal diseases including discomfort, pressure, or pain in your chest, neck, jaw, arms, calves, or other areas potentially related to ischemia; shortness of breath at rest or with mild exertion; dizziness or fainting (syncope); difficulty breathing while lying flat (orthopnea) or sudden nighttime breathing difficulties (paroxysmal nocturnal dyspnea); palpitations or rapid heartbeat (tachycardia); pain or cramping in your legs during physical activity (intermittent claudication); a known heart murmur; swelling in your ankles (edema); unusual fatigue or shortness of breath during routine activities or at rest.

• Hui-Ying Luk, PhD; Danielle Levitt, PhD, Principal investigator, Texas Tech University