A striking effect of old age is the involuntary loss of muscle mass and strength leading to sarcopenia and reduced physiological functions. However, effects of heavy-load exercise in older adults on diseases and functions as predicted by changes in muscle gene expression have been inadequately studied. Thigh muscle global transcriptional activity (transcriptome) was analyzed in cohorts of older and younger adults before and after 12–13 weeks heavy-load strength exercise using Affymetrix microarrays. Three age groups, similarly trained, were compared: younger adults (age 24 ± 4 years), older adults of average age 70 years (Oslo cohort) and above 80 years (old BSU cohort). To increase statistical strength, one of the older cohorts was used for validation. Ingenuity Pathway analysis (IPA) was used to identify predicted biological effects of a gene set that changed expression after exercise, and Principal Component Analysis (PCA) was used to visualize differences in muscle gene expressen between cohorts and individual participants as well as overall changes upon exercise. Younger adults, showed few transcriptome changes, but a marked, significant impact was observed in persons of average age 70 years and even more so in persons above 80 years. The 249 transcripts positively or negatively altered in both cohorts of older adults (q-value < 0.1) were submitted to gene set enrichment analysis using IPA. The transcripts predicted increase in several aspects of “vascularization and muscle contractions”, whereas functions associated with negative health effects were reduced, e.g., “Glucose metabolism disorder” and “Disorder of blood pressure”. Several genes that changed expression after intervention were confirmed at the genome level by containing single nucleotide variants associated with handgrip strength and muscle expression levels, e.g., CYP4B1 (p = 9.2E-20), NOTCH4 (p = 9.7E-8), and FZD4 (p = 5.3E-7). PCA of the 249 genes indicated a differential pattern of muscle gene expression in young and elderly. However, after exercise the expression patterns in both young and old BSU cohorts were changed in the same direction for the vast majority of participants. The positive impact of heavy-load strength training on the transcriptome increased markedly with age. The identified molecular changes translate to improved vascularization and muscular strength, suggesting highly beneficial health effects for older adults.

中文翻译：

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老年人的大负荷运动会激活血管生成，并且对肌肉基因表达的影响比年轻人更强


老年的一个显着影响是肌肉质量和力量的非自愿损失，导致肌肉减少症和生理功能下降。然而，通过肌肉基因表达的变化预测的老年人大负荷运动对疾病和功能的影响尚未得到充分研究。使用 Affymetrix 微阵列分析老年人和年轻人在 12-13 周大负荷力量运动前后的大腿肌肉整体转录活性（转录组）。对受过类似训练的三个年龄组进行了比较：年轻人（年龄 24 ± 4 岁）、平均年龄 70 岁的老年人（奥斯陆队列）和 80 岁以上（老 BSU 队列）。为了提高统计强度，使用了一个较老的队列进行验证。 Ingenuity Pathway分析（IPA）用于识别运动后表达变化的基因组的预测生物效应，主成分分析（PCA）用于可视化队列和个体参与者之间肌肉基因表达的差异以及运动后的总体变化锻炼。较年轻的成年人几乎没有表现出转录组变化，但在平均年龄 70 岁的人中观察到了显着的影响，在 80 岁以上的人中更是如此。两组老年人（q 值 < 0.1）中的 249 个转录本发生正向或负向改变，并使用 IPA 进行基因集富集分析。转录本预测“血管化和肌肉收缩”的几个方面会增加，而与负面健康影响相关的功能会减少，例如“葡萄糖代谢紊乱”和“血压紊乱”。 通过包含与握力和肌肉表达水平相关的单核苷酸变异，在基因组水平上确认了干预后表达发生变化的几个基因，例如 CYP4B1 (p = 9.2E-20)、NOTCH4 (p = 9.7E-8) 和FZD4（p = 5.3E-7）。 249 个基因的 PCA 表明年轻人和老年人的肌肉基因表达存在差异模式。然而，运动后，绝大多数参与者的年轻和老年 BSU 队列的表达模式都发生了相同的方向变化。大负荷力量训练对转录组的积极影响随着年龄的增长而显着增加。已确定的分子变化可改善血管化和肌肉力量，这表明对老年人的健康非常有益。