背景:老年的显着影响是肌肉质量和力量的不自主损失,导致肌肉减少症和生理功能降低。然而,通过肌肉基因表达的变化预测,老年人的重负荷运动对疾病和功能的影响尚未得到充分研究。
方法:使用Affymetrix微阵列分析了在12-13周重负荷力量运动前后的老年和年轻成人队列中大腿肌肉的整体转录活性(转录组)。三个年龄组,同样受过训练,进行了比较:年轻人(24岁±4岁),平均年龄70岁(奥斯陆队列)和80岁以上(旧BSU队列)的老年人。为了增加统计强度,其中一个较老的队列用于验证.独创性通路分析(IPA)用于确定运动后改变表达的基因集的预测生物学效应,和主成分分析(PCA)用于可视化队列和个体参与者之间的肌肉基因表达差异以及运动后的总体变化。
结果:年轻人,显示几乎没有转录组变化,而是一个标记的,在平均年龄70岁的人中观察到重大影响,在80岁以上的人中更是如此。使用IPA对两组老年人群(q值<0.1)的249个转录本进行了基因集富集分析。转录本预测“血管化和肌肉收缩”几个方面的增加,而与负面健康影响相关的功能减少,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体,在基因组水平上证实了干预后表达改变的几个基因。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。然而,运动后,绝大多数参与者在年轻和老年BSU队列中的表达模式都向同一方向改变.
结论: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著增加。确定的分子变化转化为改善的血管形成和肌肉力量,表明对老年人有非常有益的健康影响。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.