Multimodal Cancer Therapy and Accelerated Brain Aging: Mechanisms, Biomarkers, and Clinical Consequences

Area of Science:

• Neuroscience
• Oncology
• Gerontology

Background:

• Cancer therapies improve survival but cause long-term neurological issues.
• Cancer treatment-related cognitive impairment (CRCI), or "chemobrain," affects many survivors.
• CRCI symptoms include cognitive deficits and neuropsychiatric issues, suggesting accelerated brain aging.

Purpose of the Study:

• To review evidence linking multimodal cancer therapy to accelerated brain aging.
• To explore molecular, cellular, and neuroimaging mechanisms involved.
• To discuss the potential of accelerated brain aging as a paradigm for CRCI.

Main Methods:

• Synthesis of clinical, molecular, and neuroimaging data.
• Review of mechanisms: oxidative stress, neuroinflammation, BBB dysfunction, senescence, epigenetics.
• Analysis of biomarkers and neuroimaging findings (MRI).

Main Results:

• Cancer therapies induce molecular and cellular changes mirroring physiological brain aging.
• Biomarkers of aging (inflammatory mediators, senescence markers) are elevated post-therapy.
• Neuroimaging shows structural and functional brain changes, including increased brain age estimates.

Conclusions:

• CRCI can be framed as accelerated brain aging.
• This paradigm may enhance risk stratification and biomarker discovery.
• It offers a pathway toward personalized survivorship care for cancer patients.