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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
32
Matching placebo
Elysium Basis TM, Elysium Health, Inc., NY, USA
Aarhus University Hospital
Aarhus N, Denmark
Presence of Satellite Cells
quantified by immunohistochemistry in muscle biopsies
Time frame: Change from baseline up to 45 days
Activation of Satellite cells
determined by immunohistochemistry and FACS
Time frame: Change from baseline up to 45 days
Presence of macrophages
determined by immunohistochemistry and FACS
Time frame: Change from baseline up to 45 days
Presence of Fibro/Adipogenic Progenitors
quantified by FACS
Time frame: Change from baseline up to 45 days
Presence of damaged muscle fibers
determined by immunohistochemistry
Time frame: Change from baseline up to 45 days
Presence of muscle regenerative fibers
determined by immunohistochemistry
Time frame: Change from baseline up to 45 days
Presence of autophagy in relation to muscle damage
determined by Western blot and PCR
Time frame: Change from baseline up to 45 days
Lipid accumulation in skeletal muscle tissue and liver
determined by magnetic resonance spectroscopy
Time frame: Change from baseline to 8 days
Blood glucose response in relation to muscle damage
determined by Continuous glucose monitoring
Time frame: Change from baseline to 8 days
Body composition (lean body mass and fat body mass)
measured by Dual energy X-ray absorptiometry
Time frame: Change from baseline to 45 days
Muscle strength
determined from maximal voluntary contraction of the m. quadriceps femoris
Time frame: Change from baseline up to 45 days
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