Senolytics as Modulators of Critical Signaling Pathways: a Promising Strategy to Combat Brain Aging and...

Area of Science:

• Neuroscience
• Cell Biology
• Gerontology

Background:

• Brain aging is a major risk factor for neurodegenerative disorders (NDDs) like Alzheimer's and Parkinson's.
• Accumulated senescent cells in the brain drive neuroinflammation, oxidative stress, and protein aggregation.
• Senescent cells promote neurodegeneration by releasing inflammatory factors and toxic proteins.

Purpose of the Study:

• To explore senolytics as a treatment for brain aging and NDDs.
• To investigate the role of senescent cells in neuroinflammation and neuronal dysfunction.
• To examine the potential of targeting specific molecular pathways involved in cellular senescence.

Main Methods:

• Review of senolytic compounds (dasatinib, fisetin, quercetin) and their effects on senescent cells.
• Analysis of the impact of senolytics on reducing toxic protein aggregates and oxidative stress.
• Investigation of key molecular pathways: mTOR, Nrf2-Keap1, AMPK, and Sirtuin 1 (SIRT1).

Main Results:

• Senolytics effectively eliminate senescent cells, mitigating brain aging hallmarks.
• Treatment reduces harmful substances like misfolded protein aggregates and reactive oxygen species.
• Modulation of mTOR, AMPK, SIRT1, and Nrf2 pathways promotes cellular repair and homeostasis.

Conclusions:

• Senolytic therapy offers a promising strategy to combat brain aging and neurodegeneration.
• Targeting senescent cells and associated molecular pathways can restore neuronal function.
• This approach addresses the cellular and molecular underpinnings of age-related neurological decline.