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Muscle proteins accumulate damage during aging and leads to the loss of muscle mass and function in older people. Exercise can increase the making of new proteins and removal of older proteins, but it is not known if the effect changes with aging or type of exercise. The investigators will determine the ability for endurance, resistance, or a combination of exercise training to remove older-damaged proteins and make newer-functional muscle proteins in groups of younger and older people. The investigators will particularly study protein that are involved with energy production (mitochondrial proteins) and force production (contractile proteins).
Hypothesis 1: Older people will have greater accumulation of damaged proteins than younger people.
Hypothesis 2: Aerobic exercise will decrease the accumulation of damaged forms of contractile and mitochondrial proteins in younger and older people.
Hypothesis 3: Resistance exercise will decrease the accumulation of damaged forms of contractile proteins in younger and older people.
The loss of muscle mass and function with age leads to high social and economic costs. Lifestyle interventions that can help maintain muscle mass and function can be beneficial to improve health and decrease the costs associated with loss of independence in the elderly. Muscle proteins accumulate damage during aging, which is suggested to lead to loss of function. The biological processes that remove damaged proteins and synthesis new proteins appear to be decreased with aging. Exercise is known to increase the processes that remove older and synthesis newer muscle proteins and may be an effect lifestyle intervention to improve muscle quality and function. Additionally, specific types of proteins appear to decay with age including contractile and mitochondrial proteins. Different types of exercise training can increase the making of specific proteins. The investigators will examine the ability for aerobic and resistance training to increase the quality of mitochondrial and contractile proteins between younger and older people.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aerobic Exercise Training | Experimental | Participants will perform 12-weeks of high intensity aerobic training. |
|
| Combined | Active Comparator | The combined group will have 12-weeks of no exercise followed by 12-weeks of combined aerobic and resistance exercise training. Assessments will be made at three time points: baseline, after 12-weeks of no training, and after 12-weeks of combined training. |
|
| Resistance Exercise Training | Experimental | Participants will perform 12-weeks of resistance exercise training. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High intensity aerobic exercise | Behavioral | Participants will perform 12-weeks of high intensity aerobic training. Training will be 5-days per week. Three days (e.g. Monday, Wednesday and Friday) will include repeated bouts of cycling for 4-minutes at ~90% maximal effort followed by 3 minutes of active rest. The other two days (e.g. Tuesday and Thursday) will be treadmill exercise for 45 minutes at 70% of maximal effort. |
| Measure | Description | Time Frame |
|---|---|---|
| Skeletal muscle protein synthesis rate | The investigators will determine the rate of incorporation of stable isotope amino acid tracers in skeletal muscle proteins during several hours of rest. The measurement will be an average resting muscle protein synthesis rate (% new muscle protein per hour) and will be performed at baseline and following 12 weeks of exercise training. | Approximately 14 weeks for the endurance or resistance training groups and approximately 28 weeks for the combined group |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| K. Sreekumaran Nair, M.D., Ph.D. | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40595512 | Derived | Pataky MW, Heppelmann CJ, Sevits KJ, Asokan AK, Kumar AP, Klaus KA, Dasari S, Kunz HE, Strub MD, Robinson MM, Coon JJ, Lanza IR, Adams CM, Nair KS. Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle. Nat Commun. 2025 Jul 1;16(1):5700. doi: 10.1038/s41467-025-60049-0. | |
| 36147777 |
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| ID | Term |
|---|---|
| D055948 | Sarcopenia |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D055070 | Resistance Training |
| ID | Term |
|---|---|
| D005081 | Exercise Therapy |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
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|
| Resistance exercise training | Behavioral | Participants will perform 12-weeks of resistance exercise training. Training will be 5-days per week of daily sessions of 60 minutes that include resistance exercise for all major muscle groups. |
|
| Combined | Behavioral | The combined group will be assessed before and after 12 weeks of no exercise training, then again following 12 weeks of combined aerobic and resistance exercise training. |
|
| Zhang X, Habiballa L, Aversa Z, Ng YE, Sakamoto AE, Englund DA, Pearsall VM, White TA, Robinson MM, Rivas DA, Dasari S, Hruby AJ, Lagnado AB, Jachim SK, Granic A, Sayer AA, Jurk D, Lanza IR, Khosla S, Fielding RA, Nair KS, Schafer MJ, Passos JF, LeBrasseur NK. Characterization of cellular senescence in aging skeletal muscle. Nat Aging. 2022 Jul;2(7):601-615. doi: 10.1038/s43587-022-00250-8. Epub 2022 Jul 15. |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D001519 | Behavior |
| D005791 |
| Patient Care |
| D013812 | Therapeutics |
| D026741 | Physical Therapy Modalities |
| D064797 | Physical Conditioning, Human |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |