Dwivedi R, Gupta R, Pahuja M, Parihar J, Tripathi M, Dada R, Tiwari P. Temporal lobe epilepsy as a model of accelerated brain aging: Roles of biological aging markers and microRNA dysregulation. World J Clin Cases 2026; 14(8): 118420 [DOI: 10.12998/wjcc.v14.i8.118420]
Corresponding Author of This Article
Prabhakar Tiwari, PhD, Senior Researcher, Department of Anatomy, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, Delhi, India. prabhakt@gmail.com
Research Domain of This Article
Clinical Neurology
Article-Type of This Article
Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Mar 16, 2026 (publication date) through Mar 27, 2026
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Journal Information of This Article
Publication Name
World Journal of Clinical Cases
ISSN
2307-8960
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Dwivedi R, Gupta R, Pahuja M, Parihar J, Tripathi M, Dada R, Tiwari P. Temporal lobe epilepsy as a model of accelerated brain aging: Roles of biological aging markers and microRNA dysregulation. World J Clin Cases 2026; 14(8): 118420 [DOI: 10.12998/wjcc.v14.i8.118420]
Rekha Dwivedi, Jasmine Parihar, Manjari Tripathi, Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
Rashmi Gupta, Rima Dada, Prabhakar Tiwari, Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, Delhi, India
Monika Pahuja, Department of Discovery, Indian Council of Medical Research, New Delhi 110029, Delhi, India
Author contributions: Dwivedi R performed the literature search, conceptualized the review theme, and drafted the initial manuscript; Gupta R contributed to literature acquisition, data interpretation, and manuscript writing; Pahuja M assisted in organizing mechanistic pathways and critically revised the scientific content; Parihar J contributed to analysis of clinical literature and manuscript synthesis; Tripathi M provided clinical expertise, refined content related to temporal lobe epilepsy phenotype and outcome interpretation, and critically reviewed the manuscript; Dada R contributed expertise on molecular aging and microRNA biology, supervised the intellectual content, and reviewed the manuscript; Tiwari P conceived the overall framework, coordinated manuscript development, integrated revisions, and finalized the manuscript; all authors read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Prabhakar Tiwari, PhD, Senior Researcher, Department of Anatomy, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, Delhi, India. prabhakt@gmail.com
Received: January 2, 2026 Revised: January 20, 2026 Accepted: February 10, 2026 Published online: March 16, 2026 Processing time: 75 Days and 2.8 Hours
Abstract
Temporal lobe epilepsy (TLE) is characterized by recurrent seizures; however, growing evidence suggests that it may represent a progressive neurological disorder, sharing key features with accelerated brain aging. Patients with chronic TLE frequently exhibit early cognitive decline, hippocampal atrophy, neuroinflammation, and neurodegenerative changes that exceed those expected for chronological age. These observations suggest that recurrent seizures and persistent network hyperexcitability may promote premature activation of biological aging pathways in the epileptic brain. This mini-review emphasizes the concept of TLE as a model of accelerated brain aging. We highlight major aging hallmarks implicated in TLE, including oxidative stress and mitochondrial dysfunction, chronic neuroinflammation (“inflammaging”), cellular senescence, impaired proteostasis, and dysregulated autophagy. Particular emphasis is placed on epigenetic aging mechanisms, with microRNAs (miRNAs) emerging as key regulators linking epileptogenesis, neuronal aging, and disease progression. Several miRNAs implicated in aging biology, such as miR-34a, miR-146a, miR-132, miR-124, and miR-21, are consistently dysregulated in TLE and may contribute to neurodegeneration, synaptic dysfunction, and drug resistance. We further discuss the clinical and translational relevance of aging markers and miRNAs as potential biomarkers for disease severity, cognitive decline, and therapeutic response. Framing TLE within the context of biological aging provides a novel perspective that may facilitate biomarker discovery and support the development of disease-modifying strategies beyond seizure suppression in TLE.
Core Tip: Temporal lobe epilepsy (TLE) is considered as a seizure disorder, but evidence indicates it is a progressive condition resembling accelerated brain aging. Patients with chronic TLE show early cognitive decline, hippocampal atrophy, neuroinflammation, and neurodegenerative changes beyond age expectations. This mini-review highlights key aging hallmarks in TLE, including oxidative stress, mitochondrial dysfunction, chronic inflammation (“inflammaging”), impaired proteostasis, and autophagy dysregulation, and emphasizes microRNAs as epigenetic regulators linking epileptogenesis to neuronal aging. Elucidating the underlying mechanisms of TLE may facilitate the identification of robust biomarkers and inform the development of disease-modifying interventions that extend beyond symptomatic seizure management.
