Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging

Area of Science:

• Pulmonary research
• Vascular biology
• Aging research

Background:

• Reactivation and dysregulation of the mTOR signaling pathway are implicated in aging and chronic lung diseases.
• The specific impact on lung microvascular progenitor cells (MVPCs), capillary function, and tissue homeostasis remains largely unknown.

Purpose of the Study:

• To investigate the role of the mTOR signaling pathway in lung microvascular progenitor cells (MVPCs).
• To determine the impact of mTOR dysregulation on MVPC function, angiogenesis, and lung tissue homeostasis in aging and chronic lung disease.

Main Methods:

• Functional, lineage, and transcriptomic analyses were employed.
• Abcg2 was used to enrich for tissue-resident MVPCs in adult mouse and human lungs.
• mTORC1 activation in MVPCs was studied in relation to stemness, angiogenic potential, and key signaling pathways (p53, Wnt).

Main Results:

• Abcg2 identifies angiogenic, tissue-resident MVPCs in adult mouse and human lungs.
• mTORC1 activation in human and mouse MVPCs decreased stemness and angiogenic potential.
• mTORC1 activation disrupted p53 and Wnt pathways, leading to loss of alveolar-capillary structure and function.

Conclusions:

• mTOR plays a critical role in maintaining MVPC function and microvascular niche homeostasis.
• A cell-based mechanism involving MVPCs contributes to tissue structure loss in lung aging and emphysema.
• Findings suggest mTOR as a potential therapeutic target for age-related lung diseases.