Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells
Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells
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DOI：
10.1016/j.bone.2003.07.005
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发表时间：
2003-12-01
期刊：
影响因子：
4.1
通讯作者：
Kassem, M
中科院分区：
文献类型：
--
作者：
Stenderup, K;Justesen, J;Kassem, M
骨形成中与骨形成相关的减少已得到充分描述。然而，细胞原因尚不清楚。因此，我们建立了年轻（年龄18-29岁，n = 6）和老年（年龄68-81岁，n = 5）供体的骨髓基质细胞（MSC）培养物。MSC连续传代直至达到最大寿命。在从年轻和老年供体建立的早期传代和晚期传代细胞中测定细胞生长、细胞衰老标志物以及成骨和成脂潜力。与来自年轻供体的细胞相比，来自老年供体的MSC表现出降低的最大寿命（24 +/-11群体密度[PD]对41 +/-10 PD，P < 0.05），并且与年轻供体细胞（0.09 +/-0.02 PD/天）相比，老年供体细胞的平均PD率（0.05 +/-0.02 PD/天）较低（P < 0.05）。在从年轻和老年供体获得的早期传代细胞中，未检测到衰老相关β-半乳糖苷酶阳性（SA β-gal（+））细胞数量和平均端粒长度的差异。然而，与年轻供体相比，来自老年供体的MSC表现出加速衰老，这通过每个PD的SA β-gal（+）细胞数量增加来证明（分别为每个PD 4% vs每个PD 0.4%）。来自年轻和老年供体的MSC能够在体外形成相似量的矿化基质，并在体内形成正常板层骨。在成脂培养基中，年轻和老年供体的培养物中形成的脂肪细胞数量相似。总之，衰老与骨祖细胞增殖能力下降有关，这表明成骨细胞数量减少而不是功能减少导致骨形成的年龄相关性减少。(C)2003年爱思唯尔公司All rights reserved.
Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching maximal life span. Cell growth, markers of cellular senescence, and osteogenic and adipogenic potential were determined in early-passage and late-passage cells established from young and old donors. MSC from old donors exhibited a decreased maximal life span compared with cells from young donors (24 +/- 11 population doublings [PD] vs 41 +/- 10 PD, P < 0.05) and mean PD rate was lower in old donor cells (0.05 +/- 0.02 PD/day) compared with young donor cells (0.09 +/- 0.02 PD/day) (P < 0.05). No differences were detected in number of senescence-associated beta-galactosidase positive (SA beta-gal(+)) cells and mean telomere length in early-passage cells obtained from young and old donors. However, MSC from old donors exhibited accelerated senescence evidenced by increased number of SA beta-gal(+) cells per PD as compared with young (4% per PD vs 0.4% per PD, respectively). MSC from young and old donors were able to form similar amounts of mineralized matrix in vitro and of normal lamellar bone in vivo. In adipogenic medium similar numbers of adipocytes formed in cultures of young and old donors. In conclusion, aging is associated with decreased proliferative capacity of osteoprogenitor cells, suggesting that decreased osteoblastic cell number, and not function, leads to age-related decrease in bone formation. (C) 2003 Elsevier Inc. All rights reserved.