Inflammaging, cellular senescence, and cognitive aging after traumatic brain injury

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Traumatic brain injury (TBI) is a major cause of neurodegeneration and cognitive decline, often mimicking age-related dementia.
• Chronic inflammation, termed 'inflammaging,' is linked to cognitive aging and may be exacerbated by TBI.
• Cellular senescence and its associated secretory phenotype (SASP) contribute to inflammaging, but their role in TBI-induced neurodegeneration requires further definition.

Approach:

• This mini-review synthesizes pre-clinical and clinical evidence connecting cellular senescence to adverse outcomes following TBI.
• It examines the current understanding of inflammaging and SASP in the context of TBI.
• The review explores the therapeutic potential of senotherapeutics, such as senolytics and senomorphics, for TBI.

Key Points:

• Cellular senescence and SASP are implicated in TBI-related neuroinflammation and cognitive dysfunction.
• Inflammaging, driven by senescence, may be a common pathway for cognitive decline in both aging and TBI.
• Senotherapeutics offer a promising, novel approach to mitigate neurodegeneration post-TBI.

Conclusions:

• Emerging evidence links cellular senescence to poor TBI outcomes and subsequent neurodegeneration.
• Targeting senescent cells with senotherapeutics presents a potential therapeutic strategy for TBI.
• Further research is needed to elucidate the precise mechanisms and optimize senotherapeutic interventions for TBI.