Lin Yu-Hsuan, Tsai Shiow-Chwen, Chuang Sheng-Ju, Harris M Brennan, Masodsai Kunanya, Chen Pei-Ni, Hsieh Chao-Chieh, Killian Theodore, Huang Chih-Yang, Kuo Chia-Hua
Laboratory of Exercise Biochemistry, University of Taipei, Taipei 111, Taiwan.
De Duve Insitute, Université Catholique de Louvain (UCL), Woluwe-Saint-Lambert B-1200, Brussels, Belgium.
Aging (Albany NY). 2021 Mar 19;13(7):9719-9731. doi: 10.18632/aging.202727.
The present study assessed the body composition trajectory of rats (N = 96) placed into 5 groups according to lifespan, using dual-energy x-ray absorptiometry every 6 months until end-of-life. A striking linearity between lifespan and bone mass percentage (not absolute bone mass) was observed. Long-lived rats show a higher bone mass percentage with a delayed insulin rise to a similar peak level as short-lived counterparts, followed by insulin declines and bone mass loss. Decreasing insulin after streptozotocin (STZ) injection caused a rapid bone mass loss (-10.5%) with a decreased 5-day survival rate to 35% in old rats (20 months). Insulin replacement to STZ-injected rats completely blocked bone mass loss and increased the survival rate to 71%. Normal old rats (20 months) had faster lean mass loss despite greater myofiber regeneration (centronucleation) compared with the young rats (4 months). Increased CD68 and CD163 cell infiltration into insulin-depleted muscle suggests a bone marrow cell exhaustion by aging muscle. Bone produces stem cells and phagocytes to continuously rejuvenate peripheral tissues. Our data suggests that aging and unsustainable life is associated with development of disproportionality between bone and the growing body size, partly due to insulin reversal from hyperinsulinemia during late life.
本研究根据寿命将96只大鼠分为5组，每6个月使用双能X线吸收法评估大鼠的身体成分轨迹，直至生命结束。观察到寿命与骨量百分比（而非绝对骨量）之间存在显著的线性关系。长寿大鼠的骨量百分比更高，胰岛素升高延迟，达到与短寿大鼠相似的峰值水平，随后胰岛素下降，骨量流失。链脲佐菌素（STZ）注射后胰岛素减少导致老年大鼠（20个月）骨量迅速流失（-10.5%），5天生存率降至35%。给注射STZ的大鼠补充胰岛素完全阻止了骨量流失，并将生存率提高到71%。与年轻大鼠（4个月）相比，正常老年大鼠（20个月）尽管肌纤维再生（中心核化）更多，但瘦体重流失更快。CD68和CD163细胞向胰岛素缺乏肌肉的浸润增加表明衰老肌肉导致骨髓细胞耗竭。骨骼产生干细胞和吞噬细胞以不断更新外周组织。我们的数据表明，衰老和不可持续的生活与骨骼和不断增长的身体大小之间不成比例的发展有关，部分原因是晚年高胰岛素血症导致胰岛素逆转。
