Age and prior exercise in vivo determine the subsequent in vitro molecular profile of myoblasts and nonmyogenic cells derived from human skeletal muscle.

The decline in skeletal muscle regenerative capacity with age is partly attributed to muscle stem cell (satellite cell) dysfunction. Recent evidence has pointed to a strong interaction between myoblasts and fibroblasts, but the influence of age on this interaction is unknown. Additionally, while the native tissue environment is known to determine the properties of myogenic cells in vitro, how the aging process alters this cell memory has not been established at the molecular level. We recruited 12 young and 12 elderly women, who performed a single bout of heavy resistance exercise with the knee extensor muscles of one leg. Five days later, muscle biopsies were collected from both legs, and myogenic cells and nonmyogenic cells were isolated for in vitro experiments with mixed or separated cells and analyzed by immunostaining and RT-PCR. A lower myogenic fusion index was detected in the cells from the old versus young women, in association with differences in gene expression levels of key myogenic regulatory factors and senescence, which were further altered by performing exercise before tissue sampling. Coculture with nonmyogenic cells from the elderly led to a higher myogenic differentiation index compared with nonmyogenic cells from the young. These findings show that the in vitro phenotype and molecular profile of human skeletal muscle myoblasts and fibroblasts is determined by the age and exercise state of the original in vivo environment and help explain how exercise can enhance muscle stem cell function in old age.

Load magnitude affects patellar tendon mechanical properties but not collagen or collagen cross-linking after long-term strength training in older adults.

BACKGROUND: Regular loading of tendons may counteract the negative effects of aging. However, the influence of strength training loading magnitude on tendon mechanical properties and its relation to matrix collagen content and collagen cross-linking is sparsely described in older adults. The purpose of the present study was to compare the effects of moderate or high load resistance training on tendon matrix and its mechanical properties. METHODS: Seventeen women and 19 men, age 62-70 years, were recruited and randomly allocated to 12 months of heavy load resistance training (HRT), moderate load resistance training (MRT) or control (CON). Pre- and post-intervention testing comprised isometric quadriceps strength test (IsoMVC), ultrasound based testing of in vivo patellar tendon (PT) mechanical properties, MRI-based measurement of PT cross-sectional area (CSA), PT biopsies for assessment of fibril morphology, collagen content, enzymatic cross-links, and tendon fluorescence as a measure of advanced glycation end-products (AGEs). RESULTS: Thirty three participants completed the intervention and were included in the data analysis. IsoMVC increased more after HRT (+ 21%) than MRT (+ 8%) and CON (+ 7%) (p < 0.05). Tendon stiffness (p < 0.05) and Young's modulus (p = 0.05) were also differently affected by training load with a reduction in CON and MRT but not in HRT. PT-CSA increased equally after both MRT and HRT. Collagen content, fibril morphology, enzymatic cross-links, and tendon fluorescence were unaffected by training. CONCLUSION: Despite equal improvements in tendon size after moderate and heavy load resistance training, only heavy. load training seemed to maintain tendon mechanical properties in old age. The effect of load magnitude on tendon biomechanics was unrelated to changes of major load bearing matrix components in the tendon core. The study is a sub-study of the LISA study, which was registered at http://clinicaltrials.gov (NCT02123641) April 25th 2014.

Mechanical properties of human patellar tendon collagen fibrils. An exploratory study of aging and sex.

Tendons are connective tissues that transmit mechanical forces from muscle to bone and consist mainly of nano-scale fibrils of type I collagen. Aging has been associated with reduced mechanical function of tendons at the whole-tendon level and also with increased glycation of tendon collagen fibrils. Yet, the mechanical effects of aging at the fibril level remain unknown. In vitro glycation has previously been reported to substantially increase fibril strength and stiffness in young rats, suggesting a potentially large effect of aging through the glycation mechanism. We therefore expected that aging would have a similar major impact on fibril mechanical properties. In addition, differences in fibril mechanical properties between men and women have never been studied. This study investigated human patellar tendon biopsies from young (26 ± 4 years) and elderly (66 ± 1 years), men and women by measuring the mechanical properties of individual collagen fibrils using a custom nano-mechanical device. There were no major mechanical differences with either age or sex, but there were modestly greater failure stress (22%) and tensile modulus at both low and high strain (16% and 26% respectively) in the elderly group. No significant differences in mechanical properties were observed between men and women. The slightly greater strength and stiffness in the elderly group are in contrasts to the age-related deficits observed for whole-tendons in vivo, although the study was not designed to investigate these minor differences.