Preservation of satellite cell number and regenerative potential with age reveals locomotory muscle bias.
Preservation of satellite cell number and regenerative potential with age reveals locomotory muscle bias.
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DOI：
10.1186/s13395-021-00277-2
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发表时间：
2021-09-04
期刊：
影响因子：
4.9
通讯作者：
Kyba M
中科院分区：
文献类型：
--
作者：
Arpke RW;Shams AS;Collins BC;Larson AA;Lu N;Lowe DA;Kyba M
虽然肌肉再生能力随着年龄的增长而下降，但这在多大程度上是由于卫星细胞内在变化与环境变化引起的，这一直存在争议。大多数衰老研究都研究了笼中久坐小鼠的后肢运动肌肉，主要是胫骨前肌，这些肌肉异常运动不足。我们分析了卫星细胞的数量在8个肌肉群，代表运动和非运动的肌肉在年轻和2岁的小鼠，并进行移植试验的低数量的后肢卫星细胞从年轻和年老的小鼠。我们发现，卫星细胞密度并没有显着下降，2岁的大部分肌肉，和一个肌肉，咬肌，显示出适度的，但统计学上显着的卫星细胞密度随年龄的增加。胫骨前肌和趾长伸肌是明显的例外，表现出显着下降。我们使用移植试验来量化自我更新。剂量稀释显示在高于非常低的阈值的自我更新中存在显著的非线性，表明卫星细胞之间竞争池内的空间。在线性范围内测定，即，移植少于1000个细胞，显示没有证据表明2岁鼠卫星细胞的细胞自主自我更新或再生潜力下降。这些数据证明了比较肌肉分析的价值，而不是过度依赖于运动肌肉，这是不使用生理老化久坐小鼠，并表明自我更新功能障碍与年龄是急剧收购在老年阶段，而不是逐渐随着时间的推移，如以前所认为的。在线版本包含补充材料，可通过10.1186/s13395 - 021 - 00277 - 2获得。
Although 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. We 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. We 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. These 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. The online version contains supplementary material available at 10.1186/s13395-021-00277-2.
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影响因子：
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