Human Muscle Aging Recreated in Lab; Decline in Contractile Force Confirmed [Reading Science]

DGIST, POSTECH Develop 3D Muscle Microtissues Using Human Cells
Comparison of Cells from 17- and 68-Year-Old Donors... Expected to Aid Research on Sarcopenia Treatments

A technology has been developed to reproduce in the lab how human muscles become thinner and weaker with age. Researchers created 3D tissues using actual human muscle cells and observed not only age-related cellular changes but also a decline in muscle contractile force. The technology is expected to be used to study human muscle aging without relying on animal testing and to evaluate candidate treatments for sarcopenia.

Daegu Gyeongbuk Institute of Science and Technology (DGIST) announced on November 5 that a research team led by Professor Kim Minseok of its Department of New Biology had jointly developed a “3D biomimetic skeletal muscle microtissue model” that reproduces human muscle aging with a team led by Professor Cho Dongwoo of the Department of Mechanical Engineering at Pohang University of Science and Technology (POSTECH).

Process of creating 3D muscle microtissues by combining muscle cells from 17- and 68-year-old donors with biomaterial derived from porcine skeletal muscle. A comparison of muscle structure, mitochondrial function, calcium responses, and contractile force confirmed age-related changes in tissues from older donors, including thinner muscle fibers and reduced contractile force. Provided by the research team.

Skeletal muscle is attached to bones and is responsible for body movement, while also playing an important role in energy metabolism. Sarcopenia, the loss of muscle mass and strength with age, is one of the main causes of limited physical activity and increased fall risk among older adults. However, traditional animal studies have biological differences from humans, while growing muscle cells on flat culture dishes makes it difficult to adequately reproduce the three-dimensional structure and contractile function of actual muscles.

The research team used muscle cells obtained from male donors aged 17 and 68. They mixed the cells with decellularized extracellular matrix, a biomaterial that supports muscle tissue, and cultured them in tiny scaffolds made using 3D printing. This produced three-dimensional microtissues in which the muscle cells were aligned in a consistent direction, as they are in actual muscle.

Comparison of the tissues made from the two donors’ cells showed that those created from the 68-year-old donor’s muscle cells had thinner muscle fibers and a lower degree of cell fusion than those from the 17-year-old donor. Inflammation-related markers were elevated, while the function of mitochondria, which produce energy for cells, was also reduced.

In particular, calcium responses involved in muscle contraction slowed, and the contractile force generated in response to electrical stimulation also declined. The researchers observed on a single experimental platform how structural and molecular changes in aging muscle were linked to an actual decline in function.

A Research Platform for Muscle Aging to Replace Animal Testing

A key feature of the study is that it can assess actual contractile function, in addition to changes in the shape of muscle cells and their genes. By reproducing the structure and function of human muscle in three dimensions, it lays the groundwork for using the technology in aging research, beyond what is possible with conventional flat cell-culture methods.

Research team photo. DGIST Professor Kim Minseok, integrated master's and PhD program student Yang Sohye, POSTECH Professor Cho Dongwoo, and Dr. Gong Jeongsik. Photo provided by DGIST.

The U.S. Food and Drug Administration (FDA) has recently been revising its rules to enable the use of testing methods other than animal testing in drug development. The research team said the technology could be developed into a nonclinical testing platform that reflects human physiological characteristics, in line with this trend.

“This study is significant because it lays the groundwork for reproducing age-related changes using human-derived cells and assessing both changes at the cellular level and actual contractile function,” Professor Kim said. “We will develop it into a useful research tool for identifying the causes of muscle aging and verifying the efficacy of candidate treatments.”

Yang Sohye, a combined master's and doctoral student in DGIST’s Department of New Biology, and Dr. Gong Jeongsik of POSTECH’s Department of Mechanical Engineering participated in the study as co-first authors. The findings were selected as a cover article in the international journal Small Science.

This content was produced with the assistance of AI translation services.