Preservation of satellite cell number and regenerative potential with age reveals locomotory muscle bias

Skeletal Muscle

Dawn A. Lowe¹  Alexie A. Larson¹  Brittany C. Collins²  Michael Kyba³  Nguyen Lu³  Ahmed S. Shams⁴  Robert W. Arpke⁵ 

[1] Department of Integrative Biology and Physiology, Medical School, University of Minnesota, Minneapolis, MN, USA;Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota, 55455, Minneapolis, MN, USA;Present address: Department of Human Genetics, University of Utah, 15 North 2030 East, 84112, Salt Lake City, UT, USA;Lillehei Heart Institute and Department of Pediatrics, Medical School, University of Minnesota, Cancer and Cardiovascular Research Building, 2231 6th Street SE, 55455, Minneapolis, MN, USA;Lillehei Heart Institute and Department of Pediatrics, Medical School, University of Minnesota, Cancer and Cardiovascular Research Building, 2231 6th Street SE, 55455, Minneapolis, MN, USA;Human Anatomy and Embryology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt;Lillehei Heart Institute and Department of Pediatrics, Medical School, University of Minnesota, Cancer and Cardiovascular Research Building, 2231 6th Street SE, 55455, Minneapolis, MN, USA;Present address: Division of Biological Sciences, University of Missouri, 105 Tucker Hall, 65211, Columbia, MO, USA;

关键词: Satellite cells;    Regeneration;    Transplantation;   

DOI  :  10.1186/s13395-021-00277-2

来源: Springer

【 摘 要 】

BackgroundAlthough muscle regenerative capacity declines with age, the extent to which this is due to satellite cell-intrinsic changes vs. environmental changes has been controversial. The majority of aging studies have investigated hindlimb locomotory muscles, principally the tibialis anterior, in caged sedentary mice, where those muscles are abnormally under-exercised.MethodsWe analyze satellite cell numbers in 8 muscle groups representing locomotory and non-locomotory muscles in young and 2-year-old mice and perform transplantation assays of low numbers of hind limb satellite cells from young and old mice.ResultsWe find that satellite cell density does not decline significantly by 2 years of age in most muscles, and one muscle, the masseter, shows a modest but statistically significant increase in satellite cell density with age. The tibialis anterior and extensor digitorum longus were clear exceptions, showing significant declines. We quantify self-renewal using a transplantation assay. Dose dilution revealed significant non-linearity in self-renewal above a very low threshold, suggestive of competition between satellite cells for space within the pool. Assaying within the linear range, i.e., transplanting fewer than 1000 cells, revealed no evidence of decline in cell-autonomous self-renewal or regenerative potential of 2-year-old murine satellite cells.ConclusionThese data demonstrate the value of comparative muscle analysis as opposed to overreliance on locomotory muscles, which are not used physiologically in aging sedentary mice, and suggest that self-renewal impairment with age is precipitously acquired at the geriatric stage, rather than being gradual over time, as previously thought.

【 授权许可】

CC BY