Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging

Area of Science:

• Gerontology and Regenerative Medicine
• Stem Cell Biology
• Exercise Physiology

Background:

• Aging is associated with stem cell dysfunction and impaired tissue regeneration.
• The molecular mechanisms underlying exercise-induced stem cell rejuvenation remain incompletely understood.
• Previous studies have not systematically investigated exercise effects across diverse stem cell types.

Purpose of the Study:

• To comprehensively map the single-cell transcriptomic changes in multiple aged stem cell compartments in response to aerobic exercise.
• To elucidate the impact of exercise on stem cell niches and intercellular communication.
• To identify molecular pathways modulated by exercise in aging stem cells.

Main Methods:

• Generation of a single-cell transcriptomic atlas of muscle, neural, and hematopoietic stem cells and their niches in young and old mice subjected to aerobic exercise.
• Whole transcriptome analysis of single myofibers.
• Comparative analysis of transcriptomic landscapes between exercised and sedentary mice of different ages.

Main Results:

• Exercise ameliorated age-associated inflammatory pathways in stem cell compartments.
• Aerobic exercise restored intercellular communication networks involving immune cells within stem cell niches.
• Significant alterations in the composition and transcriptomic profiles of circulating and tissue-resident immune cells were observed post-exercise.
• Exercise modulated gene expression in muscle, neural, and hematopoietic stem cells and their progeny.

Conclusions:

• Aerobic exercise exerts a broad rejuvenating effect on multiple aged stem cell systems.
• Exercise counteracts aging-related inflammation and enhances cellular communication critical for tissue regeneration.
• This study provides a detailed molecular blueprint of exercise's benefits for aged stem cells and their microenvironments.