Heavy-load exercise in older adults activates vasculogenesis and has a stronger impact on muscle gene expression than in young adults

Abstract

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.

Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease

“…Several of the healthy and osteoporotic women were also included in a project to study the impact of 12 weeks of heavy-load exercise on muscle strength, balance performance and BMD. Both groups reached the same results regarding all test parameters [55,56]. Also, the lifestyle parameters were similar between groups [24].…”

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

“…Three other key crosstalk genes were also identified: ARHGEF10 , CST6 , and ROBO3 , which may contribute to bone and muscle metabolism. ARHGEF10 regulates the function of vascular endothelial cells by contributing to cell junction disruption and reorientation ( Abiko et al, 2015 ; Khan et al, 2021 ), and vascular function plays significant role in bone regeneration after damage ( Gautvik et al, 2022 ; Qin et al, 2022 ). CST6, an extracellular polypeptide inhibitor of cysteine proteases, also affects bone metastasis by regulating osteoclastogenesis in many cancers, such as breast cancer and multiple myeloma ( Li et al, 2021 ; Gai et al, 2022 ).…”