Temporal lobe epilepsy as a model of accelerated brain aging: Roles of biological aging markers and microRNA dysregulation

Table 1 Biological aging hallmarks implicated in temporal lobe epilepsy and their associated dysregulated microRNAs

Ref.	Biological aging hallmark	Key pathological features in TLE	Representative dysregulated miRNAs	Functional implications
Waldbaum et al[20], 2010; Fabisiak et al[21], 2022; Sano et al[30], 2012	Oxidative stress and mitochondrial dysfunction	Excess ROS generation during seizures; mitochondrial DNA damage; impaired ATP production	miR-34a	Promotes neuronal apoptosis, mitochondrial dysfunction, and energetic failure
Parsons et al[22], 2022; Fan et al[31], 2020; Huang et al[45], 2019	Chronic neuroinflammation (inflammaging)	Persistent microglial and astrocytic activation; elevated IL-1β, TNF-α, IL-6	miR-146a, miR-132	Sustains inflammatory signaling, synaptic dysfunction, and network instability
Tai et al[5], 2018; López-Otín et al[17], 2013; Horvath et al[28], 2018	Cellular senescence	Senescent neurons and glia; secretion of pro-inflammatory SASP factors	miR-34a	Drives irreversible growth arrest, neuroinflammation, and neurodegeneration
Toscano et al[14], 2023; López-Otín et al[17], 2013; Jimenez-Mateos et al[29], 2011	Impaired proteostasis	Protein misfolding; ER stress; defective ubiquitin-proteasome system; tau accumulation	miR-132	Disrupts protein homeostasis and accelerates neurodegeneration
Fabisiak et al[21], 2022; Henshall et al[27], 2016; Jimenez-Mateos et al[29], 2011	Dysregulated autophagy	Impaired autophagic flux; accumulation of damaged organelles	miR-132, miR-34a	Reduces neuronal survival and promotes epileptogenesis
Chang et al[12]; Henshall et al[27], 2016; 2012; Jimenez-Mateos et al[29], 2011,	Synaptic dysfunction and cognitive decline	Loss of synaptic plasticity; memory and executive impairment	miR-132, miR-134	Alters synaptic remodeling, learning, and memory circuits
Zeng et al[24], 2022; Löscher et al[26], 2021; Fan et al[31], 2020; Wang et al[43], 2021	Gliosis and drug resistance	Astrocytic hypertrophy; altered neurotransmitter homeostasis; increased drug transporter expression	miR-146a, miR-21	Contributes to pharmacoresistance and progressive network dysfunction

TLE: Temporal lobe epilepsy; ROS: Reactive oxygen species; ATP: Adenosine triphosphate; miRNA: MicroRNA; IL-1β: Interleukin-1 beta; TNF-α: Tumor necrosis factor-alpha; IL-6: Interleukin-6; SASP: Senescence-associated secretory phenotype; ER: Endoplasmic reticulum.