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Molecular Mechanisms Driving Metastatic Progression Within the Aged Tumor Microenvironment
Sudhir Kumar1, Jagdish Chand2, Preeti Sharma3
1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
International Journal of Molecular Sciences
|December 11, 2025
Summary
Aging promotes cancer metastasis through the tumor microenvironment (TME). Key factors include cellular senescence, chronic inflammation, and immune decline, creating conditions ripe for cancer spread in older adults.
Area of Science:
- Oncology
- Gerontology
- Immunology
Background:
- Metastasis is the primary cause of cancer mortality, with aging significantly influencing its progression.
- Increasing global life expectancy leads to a rise in cancer incidence and complexity in older adults.
- Understanding the aging tumor microenvironment (TME) is crucial for addressing metastasis in elderly populations.
Purpose of the Study:
- To review the molecular and cellular mechanisms by which the aged TME promotes cancer metastasis.
- To explore the interplay of aging hallmarks like senescence, inflammaging, and immune decline in facilitating metastatic development.
- To discuss emerging therapeutic strategies targeting age-related pro-metastatic factors.
Main Methods:
- Literature review of molecular and cellular mechanisms in the aged TME.
- Analysis of aging hallmarks: cellular senescence, inflammaging, immune senescence, ECM remodeling, and angiogenesis.
- Examination of molecular pathways (e.g., TGF-β, STAT3, MAPK) and aging drivers (e.g., telomere shortening, DNA damage).
Main Results:
- Accumulated senescent cells secrete SASPs, remodeling the ECM and activating pro-metastatic pathways (EMT, invasion).
- Chronic inflammation and immune decline create an immunosuppressive TME, aiding immune evasion.
- Vascular and metabolic changes, including hypoxia, support aggressive cancer growth and metastasis.
- Molecular aging hallmarks contribute to genetic instability, fostering a pro-metastatic stroma.
Conclusions:
- The aged TME presents a complex milieu that significantly enhances cancer metastasis.
- Therapeutic strategies like senolytics, anti-inflammatories, and immune modulation show promise.
- Age-specific models and precision medicine are vital for improving outcomes in elderly cancer patients.
Keywords:
agingaging hallmarkscancercellular senescenceimmune dysfunctionmetastasismolecular mechanismtumor microenvironmentMore Related Videos
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