Chronic subdural hematoma through the hallmarks of aging: a geroscience framework for the commonest neurosurgical...

Chronic subdural hematoma (CSDH) is among the commonest cranial neurosurgical conditions of older adults and is projected, on the basis of incidence modeling, to become the most common cranial neurosurgical condition in adults by 2030. Despite this clinical centrality, CSDH has not been formally examined through the conceptual lens of geroscience. This minireview reframes CSDH as a geroscience disease by mapping its pathogenesis onto the twelve hallmarks of aging articulated by López-Otín and colleagues. Two hallmarks have strong direct support in the existing CSDH literature. Chronic inflammation and altered intercellular communication both manifest in the inflammaging fingerprint of hematoma fluid and in the dysregulated paracrine signaling of the outer neomembrane. Cellular senescence is the most fertile moderate-evidence hallmark. The molecular signature of the senescence-associated secretory phenotype overlaps closely with the cytokine, chemokine, and matrix remodeling milieu of the CSDH cavity, but no study has yet demonstrated senescent cells in resected neomembrane tissue. Mitochondrial dysfunction, deregulated nutrient sensing, and loss of proteostasis have weak inferential support. Four hallmarks, namely, genomic instability, telomere attrition, epigenetic alterations, and stem cell exhaustion, are essentially unstudied in CSDH and are framed as research priorities. Disabled macroautophagy and dysbiosis have recently received initial direct measurements but remain only partially addressed. The 2024 randomized trials of middle meningeal artery embolization, the success of atorvastatin in the ATOCH trial, and emerging senolytic clinical translation collectively suggest that CSDH may be a tractable target for future mechanism-directed gerotherapeutic interventions. The most actionable contribution of this framework is to specify which experiments would convert CSDH from a surgical emergency of older adults into an exemplar of clinical geroscience.