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Restoring resident tissue macrophages to combat aging and cancer
Matthew D Park1,2,3, Nader Yatim1,2,3, Jing Zhang1,2,3
1Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract:
Perturbations to the immune system influence organismal aging, yet identifying effective therapeutic targets that mitigate aging-related tissue decline or the pathogenesis of aging-related diseases, such as cancer, remains challenging. In this Perspective, we focus on the dysfunction and loss of resident tissue macrophages (RTMs) with aging of certain tissues, which promote local inflammation, compromise tissue health and contribute to tumorigenesis. The abnormal genesis of RTMs from the bone marrow is a defining hallmark of both healthy and unhealthy aging. So, we propose that restoring RTMs-either by reshaping their niche and rescuing local self-renewal or by rejuvenating aging-associated myelopoiesis in the bone marrow-should be a major objective of interventions to promote healthy aging. We summarize the body of work supporting this conceptual framework and outline key future directions for the development of versatile myeloid-targeting therapies.
Insights
Restoring resident tissue macrophages (RTMs) is key to healthy aging. Targeting RTMs can mitigate age-related tissue decline and diseases like cancer by addressing their dysfunction and abnormal bone marrow genesis.
Area of Science:
- Immunology
- Aging Research
- Tissue Biology
Background:
- Immune system perturbations impact organismal aging.
- Identifying therapeutic targets for aging and related diseases like cancer is challenging.
- Resident tissue macrophages (RTMs) dysfunction with aging promotes inflammation, tissue compromise, and tumorigenesis.
Purpose of the Study:
- To propose restoring RTMs as a therapeutic strategy for healthy aging.
- To highlight the role of RTMs dysfunction in aging-related tissue decline and cancer.
- To outline future directions for myeloid-targeting therapies.
Main Methods:
- This perspective summarizes existing research on RTMs and aging.
- It reviews the concept of RTMs dysfunction and abnormal genesis from bone marrow.
- It discusses strategies for RTMs restoration, including niche reshaping and bone marrow rejuvenation.
Main Results:
- Aging is characterized by RTMs dysfunction and abnormal genesis from the bone marrow.
- This RTMs dysfunction contributes to local inflammation, compromised tissue health, and tumorigenesis.
- Restoring RTMs offers a promising avenue for interventions promoting healthy aging.
Conclusions:
- Restoring resident tissue macrophages (RTMs) is a critical objective for promoting healthy aging.
- Therapeutic strategies should focus on reshaping the RTM niche, enhancing local self-renewal, or rejuvenating bone marrow myelopoiesis.
- Development of versatile myeloid-targeting therapies is essential for addressing aging-related tissue decline and diseases.
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