Features of Mitochondrial Dynamics Changes in Large Pyramidal Neurons of the Human Motor Cortex during Aging

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Tatiana I. Baranich^1,2,a*, Dmitry N. Voronkov¹, Kseniia M. Okulova^1,3, Ekaterina V. Shcherbak⁴, Anna V. Egorova^1,3, Olga V. Velts^1,3, Maria S. Ryabova^1,3, Kristina A. Skvortsova^1,3, Zainab M. Omarova³, Dmitry A. Kharlamov⁵, Valeria V. Glinkina¹, and Vladimir S. Sukhorukov^1,3

¹Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia

²I. M. Sechenov First Moscow State Medical University (Sechenov University), 125009 Moscow, Russia

³Pirogov Russian National Research Medical University, 117513 Moscow, Russia

⁴City Clinical Hospital No. 1 named after N. I. Pirogov, 119049 Moscow, Russia

⁵V. F. Voyno-Yasenetsky Scientific and Practical Center of Specialized Medical Care for Children, 119620 Moscow, Russia

^* To whom correspondence should be addressed.

Received: December 25, 2025; Revised: January 29, 2026; Accepted: January 30, 2026

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Brain aging is a physiological process characterized by various neurodegenerative manifestations, largely driven by mitochondrial dysfunctions, including changes in mitochondrial metabolism and dynamics. Conflicting reports in the literature regarding mitochondrial fusion and fission in the human cerebral cortex during aging underscore the need to elucidate the mechanisms of this dysfunction. The aim of this study was to assess features of mitochondrial dynamics in the large pyramidal neurons of the human motor cortex during aging. The study was conducted on autopsy material from the motor cortex of individuals aged 75 years and older. The control group consisted of similar material from individuals aged 35-44 years who died from sudden cardiac death. Intensity of immunohistochemical staining for TOMM20, Drp1, Mfn1, Mfn2, and Opa1 proteins in the large pyramidal neurons of the human motor cortex was evaluated. Decrease in the staining intensity of TOMM20 and Opa1 markers and increase in the staining intensity of the Drp1 marker were observed, indicating enhanced mitochondrial fragmentation in the pyramidal neurons of layer V of the motor cortex, possibly associated with reduction in the mitochondrial pool volume due to dysfunction in the mitochondrial fusion process, which impedes organelle growth.

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KEY WORDS: aging, mitochondrial dynamics, fusion, fission, motor cortex, brain, neurodegeneration, adaptation

DOI: 10.1134/S0006297925604447

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