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衰老和性别对 F344BN 大鼠模型肌肉质量和 Akt-mTOR-p70s6k 相关信号转导调节的影响。

Effects of aging and gender on muscle mass and regulation of Akt-mTOR-p70s6k related signaling in the F344BN rat model.

机构信息

Department of Biological Sciences, Marshall University, Huntington, WV, USA.

出版信息

Mech Ageing Dev. 2010 Mar;131(3):202-9. doi: 10.1016/j.mad.2010.01.008. Epub 2010 Feb 12.

DOI:10.1016/j.mad.2010.01.008
PMID:20153766
Abstract

Sarcopenia is the loss of muscle mass and strength which occurs with aging. Whether the molecular basis of sarcopenia differs with muscle type and across sex is not well understood. Here we examine how aging affects the regulation of protein kinase B (Akt), the mammalian target of rapamycin (mTOR), AMP activated kinase (AMPK), p70 ribosomal S6 kinase (p70s6k), S6 ribosomal protein (rps6) and calcineurin (CaN) in the slow soleus and fast extensor digitorum longus (EDL) muscles of 6- (adult), 30- (aged), and 36-month (very aged) male and 6- (adult), 26- (aged), and 30-month (very aged) female Fischer 344xBrown Norway (F344BN) rats. In male animals, soleus and EDL muscle to body weight ratios decreased steadily with age while in the females, losses remained unchanged after 26 months. These age-related changes in the degree of muscle atrophy across sex were associated with differences in the regulation of Akt, mTOR, and p70s6k in the slow-twitch soleus and the regulation of AMPK, 4EBP1, p70s6k and rpS6 in the fast-twitch EDL. Irrespective of muscle type, aging in both the genders was associated with increased calcineurin expression. Taken together, these data suggest that indices of protein synthesis and muscle adaptation are regulated differently with aging in different muscle types and sex.

摘要

肌肉减少症是随着年龄增长而发生的肌肉质量和力量的丧失。肌肉减少症的分子基础是否因肌肉类型和性别而异,目前还不是很清楚。在这里,我们研究了衰老如何影响蛋白激酶 B(Akt)、雷帕霉素的哺乳动物靶标(mTOR)、AMP 激活的蛋白激酶(AMPK)、p70 核糖体 S6 激酶(p70s6k)、核糖体蛋白 S6(rps6)和钙调神经磷酸酶(CaN)在 6 个月(成年)、30 个月(老年)和 36 个月(非常老年)雄性和 6 个月(成年)、26 个月(老年)和 30 个月(非常老年)雌性 Fischer 344xBrownNorway(F344BN)大鼠的慢收缩比目鱼肌和快收缩伸趾长肌中的调节。在雄性动物中,比目鱼肌和伸趾长肌与体重的比值随着年龄的增长而稳步下降,而在雌性动物中,这一比值在 26 个月后保持不变。这种跨性别肌肉萎缩程度的年龄相关变化与 Akt、mTOR 和 p70s6k 在慢收缩比目鱼肌中的调节以及 AMPK、4EBP1、p70s6k 和 rpS6 在快收缩伸趾长肌中的调节不同有关。无论肌肉类型如何,两性的衰老都与钙调神经磷酸酶表达的增加有关。总之,这些数据表明,不同肌肉类型和性别的蛋白质合成和肌肉适应性的指标随年龄的变化而不同。

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