Human skeletal muscle aging atlas.

Area of Science:

• Gerontology
• Cell Biology
• Muscle Physiology

Background:

• Skeletal muscle aging contributes significantly to age-related frailty and sarcopenia.
• Understanding cellular and molecular changes in aging muscle is crucial for global health.

Purpose of the Study:

• To comprehensively map the aging process in adult human intercostal muscle at the single-cell and single-nucleus level.
• To identify specific cellular changes, including in muscle stem cells, myofibers, and the neuromuscular junction, associated with aging.
• To create a valuable resource for studying muscle aging across species.

Main Methods:

• Single-cell and single-nucleus RNA sequencing of 90,902 cells and 92,259 nuclei from 17 adult human donors.
• Analysis of cellular changes across different muscle compartments.
• Comparative analysis with an in-house mouse muscle atlas.

Main Results:

• Distinct muscle stem cell subsets show decreased ribosome biogenesis and increased CCL2 expression, leading to varied aging phenotypes.
• Expansion of nuclei at the neuromuscular junction suggests potential re-innervation.
• Loss of fast-twitch myofibers is counteracted by regeneration and the upregulation of fast-type markers in slow-twitch myofibers.
• The aging muscle microenvironment actively attracts immune cells.

Conclusions:

• This study provides a detailed atlas of human skeletal muscle aging, revealing key cellular mechanisms and adaptations.
• The findings offer insights into frailty and sarcopenia, with implications for developing targeted interventions.
• The presented resource facilitates cross-species research on muscle aging.