Serum from older donors weakened contractions in a laboratory model of human muscle tissue
Serum from older donors weakened contractions in a laboratory model of human muscle tissue
On August 12, npj Aging published a study of three-dimensional muscle tissue grown from human cells. After 48 hours in a medium containing pooled serum from donors aged 65–71 years, the tissue contracted with approximately one-third less force than tissue cultured with serum from donors aged 17–29 years. The authors also linked this effect to NF-κB activation and tested quercetin in the model.
Sarcopenia, the age-related loss of muscle mass and strength, causes muscles to weaken. Earlier experiments showed that serum and plasma from older people reduce the size of mouse muscle cells. The authors of the new study tested whether this effect also occurs in cells taken from human muscle tissue and whether tissue assembled from these cells loses its ability to contract.
They used myoblasts, which are muscle precursor cells, to grow three-dimensional tissue in plate wells containing flexible micropillars. An electrical pulse causes the tissue to contract, and the displacement of the pillars indicates the force of contraction. After seven days of growth, the authors added 10% pooled serum from either young or older donors to the medium for 48 hours.
In a two-dimensional cell culture, serum from older donors reduced muscle cell area. In the three-dimensional tissue, contraction force was approximately 30% lower. The authors therefore observed both a change in the cells and a loss of strength in the tissue assembled from them.
In the spring, a chip developed at the University of California, Berkeley showed how serum from donors aged 62+ induced signs of aging in human adipose and liver tissues over four days. The new study examines how the age-related composition of serum affects skeletal muscle and measures the resulting change in contraction.
For comparison, the authors added dexamethasone, a drug used to induce muscle atrophy in laboratory models. It also reduced cell area and contraction force, but it altered a different set of genes. In tissue exposed to serum from older donors, NF-κB, a protein that activates some inflammatory genes, was more active. Genes involved in the breakdown of muscle proteins also became more active. A separate measurement confirmed increased NF-κB activation.
Quercetin, a plant compound, reduced the decline in cell area and contraction force, as well as NF-κB activation. This model makes it possible to compare interventions using two outcomes at the same time: cell size and tissue contraction force.