Muscle Injury
Conditions
Brief summary
Successful skeletal muscle regeneration depends on a functional pool of muscle stem cells, termed satellite cells (SC). SC are in a quiescent state throughout adulthood, but undergo multiple cycles of proliferation and self-renewal in response to muscle damage. During aging, there is a loss of SC quiescence, and SC more readily enter an ageing-state impairing their function. Animal studies have revealed a common denominator for increasing SC function and activity, namely Sirtuin activation. Natural stimulators of Sirtuins includes Nicotinamide Riboside (NR) (a Nicotinamide adenine dinucleotide (NAD+) precursor) and the polyphenol Pterostilbene (PT). In this study, we aim to investigate if NR+PT supplementation will promote skeletal muscle regeneration after muscle damage in elderly humans by enhanced recruitment of SC.
Detailed description
14 days after start of placebo or NR/PT (500/100 mg twice daily) supplementation a muscle damage will induced in the m. vastus lat. by electric stimulation combined with eccentric work in a dynamometer. Muscle biopsies will be collected at 2 hours, 2, 8 and 30 days post damage and placebo or NR/PT supplementation will continue for the whole study period (45 days).
Interventions
Matching placebo
OTHERNicotinamide Riboside/Pterostilbene (500 mg/100 mg twice daily)
Elysium Basis TM, Elysium Health, Inc., NY, USA
Sponsors
University of Copenhagen
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Written signed consent * Age: 55-80 * BMI: 20-28 (kg/(m2)) * Non-smoker
Exclusion criteria
* Endocrine disease, neurological or muscle disease * Other severe disease * High daily activity level (\>30 min / day)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Satellite Cells | Change from baseline up to 45 days | quantified by immunohistochemistry in muscle biopsies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Activation of Satellite cells | Change from baseline up to 45 days | determined by immunohistochemistry and FACS |
| Presence of macrophages | Change from baseline up to 45 days | determined by immunohistochemistry and FACS |
| Presence of Fibro/Adipogenic Progenitors | Change from baseline up to 45 days | quantified by FACS |
| Presence of damaged muscle fibers | Change from baseline up to 45 days | determined by immunohistochemistry |
| Muscle strength | Change from baseline up to 45 days | determined from maximal voluntary contraction of the m. quadriceps femoris |
| Presence of autophagy in relation to muscle damage | Change from baseline up to 45 days | determined by Western blot and PCR |
| Lipid accumulation in skeletal muscle tissue and liver | Change from baseline to 8 days | determined by magnetic resonance spectroscopy |
| Blood glucose response in relation to muscle damage | Change from baseline to 8 days | determined by Continuous glucose monitoring |
| Body composition (lean body mass and fat body mass) | Change from baseline to 45 days | measured by Dual energy X-ray absorptiometry |
| Presence of muscle regenerative fibers | Change from baseline up to 45 days | determined by immunohistochemistry |
Countries
Denmark
Outcome results
None listed