bims-mistre 2026-02-15 papers

bims-mistre

Biomed News

on Mito stress

Issue of 2026–02–15
nine papers selected by
Ellen Siobhan Mitchell, MitoQ

Molecular Mechanisms of Accelerated Ageing in Geriatric Depression: Interplay of Telomere Attrition, Mitochondrial Dysfunction and Cellular Senescence.
Targeting the powerhouse: the mitochondrial perspective on gentamicin-induced kidney injury.
Effects of coenzyme Q10 analogs on oxidative stress, muscle, and metabolism after exercise: A meta-analysis and systematic review.
Mitochondrial DNA: a molecular switch driving sterile neuroinflammation.
Is Higher Antioxidant Capacity an Important Determinant of Cognitive Performance? Editorial Highlight on "Brain Glutathione Levels Associate With Cognitive Performance in Older Adults" by Lee et al.
Estrogen regulates cognitive function in APP/PS1 female mice via modulation of IDO1-mediated Trp/Kyn metabolism through ERβ.
Assessing the Roles of Aging, Estrogen, Nutrition, and Neuroinflammation in Women and Their Involvement in Alzheimer's Disease-A Narrative Overview.
Reproductive factors, insulin resistance surrogate indices, and circadian syndrome among middle-aged and elderly women a mediation analysis using two-national cohorts.
Circulating mitochondrial and cellular damage markers in long COVID: Links to cognitive function, psychological distress, and inflammation.

Int J Mol Sci. 2026 Feb 06. pii: 1613. [Epub ahead of print]27(3):

Molecular Mechanisms of Accelerated Ageing in Geriatric Depression: Interplay of Telomere Attrition, Mitochondrial Dysfunction and Cellular Senescence.

Pratibha Revi Shanker, Rajkumar Dorajoo.

  Late-life depression is a prevalent and debilitating disorder. It differs significantly from depression in younger adults and often co-occurs with cognitive decline and increased physical frailty. This narrative review explores the role of accelerated biological ageing in late-life depression. We examine evidence linking three interconnected processes, namely telomere attrition, mitochondrial dysfunction and cellular senescence, to the pathophysiology of late-life depression. Excessive attrition of telomeres may serve as a biomarker of accumulated stress and cellular ageing. Mitochondrial dysfunction not only reduces energy production but also promotes oxidative stress and inflammation that increase neuroinflammatory pathways and synaptic loss. Increased cellular senescence further induces senescence-associated secretory phenotype factors that drive chronic inflammation and neuronal loss. Together, these processes create a cycle of cellular stress, persistent inflammation and damage to brain circuits involved in late-life depression. We additionally highlight potential limitations in current findings and propose a roadmap for future research to better elucidate the mechanistic dysfunction of late-life depression. These include the need for evaluation in long-term prospective cohort studies, improved tools to better correlate blood-based markers with changes in disease-relevant brain tissues and regions, and trials that test treatment and lifestyle modifications that are targeted at ageing biomarkers.

Keywords:  apoptosis; depression; inflammation; mitochondria; telomere length

DOI:  https://doi.org/10.3390/ijms27031613
Arch Toxicol. 2026 Feb 07.

Targeting the powerhouse: the mitochondrial perspective on gentamicin-induced kidney injury.

Busra Korkut Celikates, Sinem Ilgin, Melis Umay Yilmaz, Ozlem Atli Eklioglu.

  Gentamicin (GEN), an aminoglycoside antibiotic, induces nephrotoxicity primarily via mitochondrial dysfunction. This review summarizes mechanisms including reactive oxygen species (ROS) overproduction, mitochondrial DNA (mtDNA) damage, impairment of oxidative phosphorylation, and mitochondrial permeability transition pore (mPTP) activation. These mitochondrial alterations lead to adenosine triphosphate (ATP) depletion, apoptosis, and renal injury. In addition to apoptotic pathways, necrotic cell death can also be triggered, further aggravating kidney damage. Furthermore, GEN has been reported to directly interfere with mitochondrial ribosomes and gene expression, highlighting mitochondria as both targets and amplifiers of cellular toxicity. Therapeutic approaches targeting mitochondrial integrity, including antioxidants and mitochondrial transplantation, demonstrate potential nephroprotection. Additional strategies such as mPTP, stimulation of mitochondrial biogenesis, and pharmacological modulators of mitochondrial respiration have also shown promise in experimental studies. Understanding mitochondrial mechanisms underlying gentamicin-induced renal injury is crucial for developing targeted therapeutic strategies. A more comprehensive knowledge of mitochondrial regulation, organelle crosstalk, and early biomarkers of dysfunction will facilitate translation into clinical practice. Overall, preserving mitochondrial function represents a promising avenue for reducing nephrotoxicity while maintaining the antibacterial efficacy of GEN.

Keywords:  Gentamicin; Mitochondrial dysfunction; Mitochondrial permeability transition pore; Nephrotoxicity; Oxidative stress; Reactive oxygen species

DOI:  https://doi.org/10.1007/s00204-026-04310-5
J Int Med Res. 2026 Feb;54(2): 3000605251411151

Effects of coenzyme Q10 analogs on oxidative stress, muscle, and metabolism after exercise: A meta-analysis and systematic review.

Yangqi Zhang, Yilang He, Mingling Ma, Hui Dong, Zijian Ma.

  ObjectiveThis study aimed to investigate whether coenzyme Q10 is effective in preventing exercise-induced oxidative stress and muscle damage.MethodsFourteen randomized controlled studies examining the effects of supplementation with coenzyme Q10 analogs on postexercise oxidative stress and muscle damage were identified through searches in literature databases, including PubMed, the Cochrane Library, Embase, and Web of Science, and then the quality of the included studies was assessed. Quantitative and qualitative analyses were performed.ResultsThe study screened 14 randomized controlled trials that included a total of 433 subjects. The results demonstrated that oral coenzyme Q10 elevated blood coenzyme Q10 concentration (standardized mean difference: 2.710, 95% confidence interval: 1.57-3.85, p < 0.00001) and reduced blood malondialdehyde concentration (standardized mean difference: -0.289, 95% confidence interval: -0.541 to -0.038, p = 0.024). Additionally, oral coenzyme Q10 was found to reduce blood creatine kinase values (standardized mean difference: -1.532, 95% confidence interval: -2.856 to -0.209, p = 0.023), suggesting a potential protective effect on skeletal muscle. The metabolism-related blood lactate and maximal oxygen uptake levels were not affected by coenzyme Q10 (standardized mean difference: -0.68, 95% confidence interval: -1.89 to 0.53, p = 0.271; standardized mean difference: -0.156, 95% confidence interval: -0.79 to 0.478, p = 0.630).ConclusionsCoenzyme Q10 may reduce exercise-induced oxidative stress on blood malondialdehyde and exert a protective effect on muscle; however, no effect was observed from the anaerobic and aerobic metabolism of the organism.

Keywords:  Coenzyme Q10; exercise; metabolism; muscle damage; oxidative stress

DOI:  https://doi.org/10.1177/03000605251411151
Transl Neurodegener. 2026 Feb 13. 15(1): 5

Mitochondrial DNA: a molecular switch driving sterile neuroinflammation.

Abhishek Jauhari, Tanisha Singh, Diane L Carlisle, Robert M Friedlander.

  Mitochondrial DNA (mtDNA) plays a pivotal role in the regulation of neuroinflammation, acting as a potent trigger of innate immune responses when released into the cytoplasm or extracellular space. mtDNA is structurally similar to bacterial DNA, containing unmethylated CpG motifs that are readily recognized by immune sensors. Under conditions of cellular stress, injury, or mitochondrial dysfunction, mtDNA can escape into the cytoplasm, where it activates the cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) signaling pathway, or it can be detected extracellularly by Toll-like receptors on immune cells. These signaling events lead to the production of pro-inflammatory cytokines and type I interferons, amplifying neuroinflammatory responses. In the central nervous system, this process contributes to the pathogenesis of various neurodegenerative and inflammatory conditions, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), etc.. The dual role of mtDNA as both a damage-associated molecular pattern and a signaling molecule underscores its importance as a therapeutic target for modulating neuroinflammation and protecting against progressive neuronal damage. In this review, we will discuss the implications of mtDNA-mediated neuroinflammation in neurodegenerative diseases, including AD, PD, and HD, highlighting its potential as a diagnostic biomarker and therapeutic target.

Keywords:  Mitochondria; Mitochondrial DNA; Neurodegeneration; Neuroinflammation

DOI:  https://doi.org/10.1186/s40035-026-00540-w
J Neurochem. 2026 Feb;170(2): e70378

Is Higher Antioxidant Capacity an Important Determinant of Cognitive Performance? Editorial Highlight on "Brain Glutathione Levels Associate With Cognitive Performance in Older Adults" by Lee et al.

João M N Duarte.

  Glutathione is a major component of the cellular antioxidant system, providing a means of controlling redox homeostasis and affording protection against oxidative damage. Proton magnetic resonance spectroscopy (MRS) offers insights into brain metabolism by enabling the noninvasive quantification of metabolites. Previous studies have demonstrated that the neurotransmitters glutamate and GABA detected by MRS show activity-dependent concentration changes and correlate with cognitive performance. Yet how MRS detected antioxidant capacity, particularly glutathione levels, relates to cognition remains unclear. In this issue, Lee et al. report that higher cortical glutathione levels are associated with better cognitive outcomes in older adults. These findings might contribute to understanding whether glutathione levels index resilience or degeneration. However, observations reported across the literature remain inconsistent, and the observed discrepancies underscore the need for further research using harmonized MRS acquisitions, deeper metabolic and cognitive phenotyping, and longitudinal study designs to clarify the role of cortical glutathione in cognitive trajectories.

Keywords:  cognition; glutathione; magnetic resonance spectroscopy; metabolism

DOI:  https://doi.org/10.1111/jnc.70378
Horm Behav. 2026 Feb 07. pii: S0018-506X(26)00016-4. [Epub ahead of print]179 105891

Estrogen regulates cognitive function in APP/PS1 female mice via modulation of IDO1-mediated Trp/Kyn metabolism through ERβ.

Lingdi Zhang, Shuang Hu, Jianjun Zhu, Guojun Jiang.

  Alzheimer's disease (AD) is more prevalent in postmenopausal women, possibly due to estrogen deficiency. IDO1 (Indoleamine 2,3-dioxygenase 1), a tryptophan-metabolizing enzyme, mediates immunomodulation and neuroinflammation and may be related to cognitive impairment in AD. This study used APP/PS1 transgenic female mice with ovariectomy (OVX),E2, IDO1 inhibitor (1-MT), and agonists and antagonists of estrogen receptors to explore the potential roles of estrogen and IDO1 in AD. Results showed that OVX aggravated the cognitive function impairment of the APP/PS1 mice. OVX also decreased the serum E2 level and increased the hippocampal IDO1 level. The application of 1-MT reversed the cognitive impairment, suggesting the elevated IDO1 level to be a contributing factor for the high susceptibility to AD in females with estrogen deficiency. Interestingly, E2 alleviated the cognitive function of the APP/PS1 mice undergoing OVX. E2 also decreased hippocampal IDO1 level and impacted the metabolism of IDO1-mediated L-Tryptophan (Trp)/kynurenine (Kyn) pathway by decreasing the levels of Kyn, Kyn-to-Trp ratio, 3-hydroxykynurenine (3-HK) and quinolinic acid (QA) and increasing the levels of serotonin (5-HT), 5-HT-to-Trp ratio, and kynurenic acid (KA). The E2's effects were similar to those of the IDO1 inhibitor. Furthermore, the ERβ antagonist could reverse the effects of E2 and the ERβ agonist had comparable effects to E2 on the Trp/Kyn pathway. These findings indicate that E2 has positive effects on the cognitive function of the APP/PS1 female mice undergoing OVX, and the mechanism may be related to the modulation of IDO1-mediated Trp/Kyn pathway via activation of ERβ.

Keywords:  APP/PS1 mice; Alzheimer's disease; IDO1; Ovariectomy; Trp/Kyn pathway

DOI:  https://doi.org/10.1016/j.yhbeh.2026.105891
Int J Mol Sci. 2026 Jan 26. pii: 1239. [Epub ahead of print]27(3):

Assessing the Roles of Aging, Estrogen, Nutrition, and Neuroinflammation in Women and Their Involvement in Alzheimer's Disease-A Narrative Overview.

Edwin D Lephart, K Scott Weber, Dawson W Hedges.

  The purpose of this narrative review is to examine women's cognitive health and to highlight its association with four major pillars: (1) aging, (2) estrogen decline and loss, (3) diet, and (4) neuroinflammation, and their contribution to cognitive decline, with a focus on this combination to increase awareness and address the progression and potential amelioration of Alzheimer's disease (AD). Often overlooked, estrogen decline during perimenopause and loss of estrogen production from the ovaries after menopause negatively influences almost every tissue and organ in the body, including the brain. This estrogen loss leads to inflammation, as can poor nutritional choices, both of which have a profound impact on short- and long-term health and can increase the risk of dementia, including AD. Thus, this overview covers the following four pillars (1) a brief background on cognitive decline and AD with aging, (2) the importance of and changes in estrogen with aging, (3) influence of dietary choices on overall well-being and brain health, and (4) the biochemical and molecular mechanisms by which this combination of factors may lead to neuroinflammation, resulting in cognitive decline and AD. Finally, this review briefly presents a hypothesis on whether women during perimenopause should be administered estrogen to span the transition into menopause to protect against cognitive decline and possibly ameliorate the risk of AD. This article is based on previously conducted studies and does not contain new data/results (studies) of human participants or animals performed by the authors.

Keywords:  Alzheimer’s disease; aging; cognitive function; estrogen; menopause; nutrition; perimenopause

DOI:  https://doi.org/10.3390/ijms27031239
Diabetes Res Clin Pract. 2026 Feb 06. pii: S0168-8227(26)00060-4. [Epub ahead of print]233 113141

Reproductive factors, insulin resistance surrogate indices, and circadian syndrome among middle-aged and elderly women a mediation analysis using two-national cohorts.

Linli Liu, Jun Lin, LinHong Li, Sanshan Wu, Zhang Shen, JinHua Chen, Y Peng, Minlan Lin, Xiafei Ye, Danru Chen, Quping Tan.

   AIMS: We investigated the mediation effects of seven insulin resistance(IR) indices: triglyceride glucose (TyG), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC), estimated glucose disposal rate (eGDR), metabolic score for IR, lipid accumulation product (LAP), and Chinese visceral adiposity index (CVAI) on the associations between reproductive factors and circadian syndrome (CircS) in middle-aged and elderly women.
METHODS: This study was conducted using the China Health and Retirement Longitudinal Study (CHARLS) as training set and the English Longitudinal Study on Aging (ELSA) as validation set, with baseline non-CircS individuals. Regression models established causal relationships between reproductive factors and incident CircS. Mediation analysis quantified IR mediation effects. Receiver operating characteristic curves evaluated IR indices' predictive capacity.
RESULTS: The incidence of new-onset CircS was 465 (15.94%) in CHARLS and 291 (11.89%) in ELSA, respectively. The CircS incidence was higher in earlier age at menarche or menopause. Mediation analyses revealed that TyG, TyG-WHtR, TyG-WC, LAP, CVAI, and eGDR mediated the menarche-CircS association, with TyG-WHtR accounting for 14.3% of the mediating effect. The TyG-WHtR cutoff value for predicting CircS was identified 4.507 for early menarche.
CONCLUSION: Significant inverse relationships were observed between early age at menarche/menopause and increased CircS risk, with IR largely mediating these associations.

Keywords:  Age at menarche; Age at menopause; Circadian syndrome; Insulin resistance; Mediation analysis

DOI:  https://doi.org/10.1016/j.diabres.2026.113141
Mol Psychiatry. 2026 Feb 07.

Circulating mitochondrial and cellular damage markers in long COVID: Links to cognitive function, psychological distress, and inflammation.

EPILOC Phase 2 Study Group

Persistent mitochondrial inflexibility and mitochondrial damage may contribute to Post-Acute Sequelae of COVID-19 (PASC). However, data linking mitochondrial biomarkers, such as circulating cell-free mitochondrial DNA (ccf-mtDNA) to long-COVID symptoms remain limited. We analyzed ccf-mtDNA relative to glycerinaldehyd-3-phosphat-dehydrogenase and total cell-free DNA (ccf-DNA) in a nested case-control study of 228 adults (PASC: n = 128, recovered controls: n = 100). Possible associations between these markers and general cognition, verbal memory, psychological distress, and inflammation were also examined. ccf-DNA (measured via UV-Vis spectroscopy), relative ccf-mtDNA (measured via quantitative real-time PCR, -ΔCT), C-reactive protein [CRP], and systemic immune-inflammation index [SII] were assessed. Principal component analysis (PCA) was applied to (neuro)psychological tests to derive three components: general cognition, verbal memory, and psychological distress, which were used in further analyses. PASC patients exhibited significantly lower cognitive function and higher psychological distress than recovered controls. They also had elevated CRP levels and lower relative ccf-mtDNA, with 25% showing low-grade inflammation. Across all participants, general cognition correlated positively with the relative ccf-mtDNA, while CRP correlated negatively with the relative ccf-mtDNA. Mediation analysis suggested relative ccf-mtDNA as a potential mediator of CRP differences between PASC and recovered controls. However, CRP differences did not remain after controlling for potential confounders (age, sex, education, smoking, body mass index, psychiatric medication). Lower relative ccf-mtDNA in PASC might indicate altered mitochondrial quality control, potentially leading to mitochondrial dysfunction, accumulation of damaged mitochondria, and increased inflammation.

DOI: https://doi.org/10.1038/s41380-026-03471-0